RxPG News : Evolution

'Primodial Soup' theory for origin of life rejected in paper

Tue, 02 Feb 2010 14:04:01 PST

( from http://www.rxpgnews.com ) For 80 years it has been accepted that early life began in a 'primordial soup' of organic molecules before evolving out of the oceans millions of years later. Today the 'soup' theory has been over turned in a pioneering paper in BioEssays which claims it was the Earth's chemical energy, from hydrothermal vents on the ocean floor, which kick-started early life.

"Textbooks have it that life arose from organic soup and that the first cells grew by fermenting these organics to generate energy in the form of ATP. We provide a new perspective on why that old and familiar view won't work at all," said team leader Dr Nick lane from University College London. "We present the alternative that life arose from gases (H2, CO2, N2, and H2S) and that the energy for first life came from harnessing geochemical gradients created by mother Earth at a special kind of deep-sea hydrothermal vent – one that is riddled with tiny interconnected compartments or pores."

The soup theory was proposed in 1929 when J.B.S Haldane published his influential essay on the origin of life in which he argued that UV radiation provided the energy to convert methane, ammonia and water into the first organic compounds in the oceans of the early earth. However critics of the soup theory point out that there is no sustained driving force to make anything react; and without an energy source, life as we know it can't exist.

"Despite bioenergetic and thermodynamic failings the 80-year-old concept of primordial soup remains central to mainstream thinking on the origin of life," said senior author, William Martin, an evolutionary biologist from the Insitute of Botany III in Düsseldorf. "But soup has no capacity for producing the energy vital for life."

In rejecting the soup theory the team turned to the Earth's chemistry to identify the energy source which could power the first primitive predecessors of living organisms: geochemical gradients across a honeycomb of microscopic natural caverns at hydrothermal vents. These catalytic cells generated lipids, proteins and nucleotides giving rise to the first true cells.

The team focused on ideas pioneered by geochemist Michael J. Russell, on alkaline deep sea vents, which produce chemical gradients very similar to those used by almost all living organisms today - a gradient of protons over a membrane. Early organisms likely exploited these gradients through a process called chemiosmosis, in which the proton gradient is used to drive synthesis of the universal energy currency, ATP, or simpler equivalents. Later on cells evolved to generate their own proton gradient by way of electron transfer from a donor to an acceptor. The team argue that the first donor was hydrogen and the first acceptor was CO2.

"Modern living cells have inherited the same size of proton gradient, and, crucially, the same orientation – positive outside and negative inside – as the inorganic vesicles from which they arose" said co-author John Allen, a biochemist at Queen Mary, University of London.

"Thermodynamic constraints mean that chemiosmosis is strictly necessary for carbon and energy metabolism in all organisms that grow from simple chemical ingredients [autotrophy] today, and presumably the first free-living cells," said Lane. "Here we consider how the earliest cells might have harnessed a geochemically created force and then learned to make their own."

This was a vital transition, as chemiosmosis is the only mechanism by which organisms could escape from the vents. "The reason that all organisms are chemiosmotic today is simply that they inherited it from the very time and place that the first cells evolved – and they could not have evolved without it," said Martin.

"Far from being too complex to have powered early life, it is nearly impossible to see how life could have begun without chemiosmosis", concluded Lane. "It is time to cast off the shackles of fermentation in some primordial soup as 'life without oxygen' – an idea that dates back to a time before anybody in biology had any understanding of how ATP is made."

Human species could have killed Neanderthal man

Wed, 22 Jul 2009 15:04:33 PST

( from http://www.rxpgnews.com ) The wound that killed a Neanderthal man between 50,000 and 75,000 years was most likely caused by a thrown spear, the kind modern humans used but Neanderthals did not, according to the latest research.

'What we've got is a rib injury, with any number of scenarios that could explain it,' said Steven Churchill, professor at Duke University.

'We're not suggesting there was a blitzkrieg, with modern humans marching across the land and executing the Neanderthals. I want to say that loud and clear,' added Churchill.

But Churchill's analysis indicates the wound was from a thrown spear, and it appears that modern humans had weapons that could be thrown and Neanderthals didn't.

'We think the best explanation for this injury is a projectile weapon, and given who had those and who didn't that implies at least one act of inter-species aggression,' he said.

He and four other investigators used a specially calibrated crossbow, copies of ancient stone points and numerous animal carcasses to make their deductions.

Neanderthals, stoutly-built and human-like, lived at the same time and in the same areas as some modern humans before going extinct.

Anthropologists have been puzzling over the fate of Neanderthals for many years, proposing that perhaps they inter-bred with modern humans, failed to compete for food or resources, or were possibly hunted to extinction by humans.

While narrowing the range of possible causes for the Iraqi Neanderthal's wound, and raising the possibility of an encounter between humans and a now-extinct close cousin, the research does not definitively conclude who did it, or why.

The victim was one of nine Neanderthals discovered between 1953 and 1960 in a cave in northeastern Iraq's Zagros Mountains. Now called 'Shanidar 3,' he was a 40- to 50-year-old male with signs of arthritis and a sharp, deep slice in his left ninth rib, said a Duke release.

The wounded Neanderthal's rib had apparently started healing before he died. Comparing the wound to medical records from the American Civil War, a time before modern antibiotics, suggested to the researchers that he died within weeks of the injury, perhaps due to associated lung damage from a stabbing or piercing wound.

'People have been speculating about that rib injury for 50 years now,' Churchill said. 'Some said it was interpersonal violence. Others said it could have been an accident. Did it involve only Neanderthals? Now we, for the first time, have brought some experimental evidence to bear on these questions.'

The report is now online in the Journal of Human Evolution.

History, geography also seem to shape our genome

Thu, 18 Jun 2009 17:59:57 PST

( from http://www.rxpgnews.com ) History and geography shape our genome, according to a new study.

The movements of humans within and among continents, expansions and contractions of populations and vagaries of genetic chance, have influenced the distribution of genetic variations.

In recent years, geneticists have identified a handful of genes that have helped human populations adapt to new environments within just a few thousand years - a strikingly short time scale in evolutionary terms.

However, a team from the Universities of Chicago, California and Stanford, which jointly conducted the study, found that for most genes, it can take at least 50,000-100,000 years for natural selection to spread favourable traits through a human population.

They found that gene variants tend to be distributed throughout the world in patterns that reflect ancient population movements and other aspects of population history.

'We don't think that selection has been strong enough to completely fine-tune the adaptation of individual human populations to their local environments,' says study co-author Jonathan Pritchard, professor in human genetics and Howard Hughes Medical Institute investigator.

'In addition to selection, demographic history -- how populations have moved around -- has exerted a strong effect on the distribution of variants,' he added.

Selection may still be occurring in many regions of the genome, said Pritchard. But if so, it is exerting a moderate effect on many genes that together influence a biological characteristic, according to a Howard Hughes release.

'We don't know enough yet about the genetics of most human traits to be able to pick out all of the relevant variation,' said Pritchard.

'As functional studies go forward, people will start figuring out the phenotypes - associated with selective signals,' said lead study author Graham Coop.

'That will be very important, because then we can figure out what selection pressures underlie these episodes of natural selection.'

The study was published in the Friday edition of the open-access journal PLoS Genetics.

Artificial human sperm could make men redundant: experts

Mon, 07 Apr 2008 11:34:58 PST

( from http://www.rxpgnews.com ) Hamburg -, April 7 - Artificial human sperm could come to the aid of infertile men, according to a team of German scientists who have used lab-grown sperm to inseminate female mice.

Artificial sperm could also make males totally redundant, permitting women to give birth without a biological male mate.

The genetic scientists at the University of Goettingen in Germany have produced 65 mouse foetuses using sperm, which was grown from embryonic stem cells, according to a Deutschlandfunk radio report.

Twelve baby mice have been born using this artificial, lab-grown sperm, said Wolfgang Engel, director of Human Genetics at the medical university.

However, the mortality rate is high, he told the German broadcaster.

'We started out with 65 embryos from egg cells which had been inseminated by the sperm-like cells created in our lab. Of those, 12 reached full term and were born.

'But seven of the newborn animals died within a period ranging from three days to five months after birth of causes which we have not been able to determine,' he said.

'So you can see that this is all still in the very early experimental stages,' he added. 'If it works in the mouse, I'm sure it will also work in the human.'

A sperm cell from an embryonic stem cell would still not give an infertile man a biological tie to his child, however. It would not be any different than using donor sperm.

Engel's team has now turned to generating sperm from very early germ cells taken from the testicles. Another possibility is to try and generate viable sperm cells using stem cells in bone marrow.

'If it works in the mouse, I'm sure it will also work in the human,' he was quoted as saying.

Engel says if sperm can be grown in the lab, it would be possible to take early germ cells from one woman, turn them into sperm cells, and use those to fertilise the egg of another woman.

But Engel said his team would stop short of tests on humans in compliance with federal law in Germany, which bans all genetic research using human stem cells.

He said one member of his team has gone to Newcastle, England, to conduct research on artificial human sperm.

New Insights Into the Nature of Pride as a Social Function

Mon, 18 Jun 2007 15:59:37 PST

( from http://www.rxpgnews.com ) Pride has perplexed philosophers and theologians for centuries, and it is an especially paradoxical emotion in American culture. We applaud rugged individualism, self-reliance and personal excellence, but too much pride can easily tip the balance toward vanity, haughtiness and self-love. Scientists have also been perplexed by this complex emotion, because it is so unlike primary emotions like fear and disgust.

University of British Columbia psychologist, Jessica Tracy, and Richard Robins of the University of California, Davis, have been exploring the origins and purpose of pride, both in the laboratory and in the field. They wanted to know if pride is as universal as, say, joy or anger.

In the June issue of Current Directions in Psychological Science, a journal of the Association for Psychological Science, Tracy and Robins review several recent studies on the nature and function of pride.

In one experiment, researchers used photographs of models with varying facial expressions and body language, asking subjects to identify the nonverbal signs of pride. And they did indeed find a prototypical prideful look, which was recognized by children as young as four, and people in many different cultures, including members of an isolated, preliterate tribe in Burkina Faso, West Africa.

So, pride appears to be universal, but that still leaves the question: What is it What is its purpose To explore this, Tracy and Robins first asked people to come up with words that they associated with pride. They found that either people link pride to such achievement-oriented ideas as accomplishment and confidence (authentic pride) or, people connect pride to self-aggrandizement, arrogance and conceit (hubristic pride).

People who tend to feel authentic pride were more likely to score high on extraversion, agreeableness, genuine self-esteem and conscientiousness. However, those who tend to feel hubristic pride were narcissistic and prone to shame. Further, they found that people who felt positive, achievement-oriented feelings of pride viewed hard work as the key to success in life, whereas hubristic people tended to view success as predetermined, due to their stable abilities.

Tracy and Robins argue that the primitive precursors of pride probably motivated our ancestors to act in altruistic and communitarian ways, for the good of the tribe, and the physical display of pride both reinforced such behavior and signaled to the group that this person was worthy of respect. So individual pride, at least the good kind, contributed in important ways to the survival of the community.

But what about pride's dark side Tracy and Robins speculate that hubris might have been a social "short cut", a way of tricking others into paying respect when it was not warranted. Those who could not earn respect the old-fashioned way figured out how to look and act accomplished in order to gain status. Social cheaters puffed themselves up because deep down they did not have what it took to succeed in their world. Whatever respect they got would have been fleeting, of course, as it is today

Girls Select Partners Who Resemble Their Dads - Research

Thu, 14 Jun 2007 16:59:37 PST

( from http://www.rxpgnews.com ) Women who enjoy good childhood relationships with their fathers are more likely to select partners who resemble their dads research suggests.In contrast, the team of psychologists from Durham University and two Polish institutions revealed that women who have negative or less positive relationships were not attracted to men who looked like their male parents.

Due to be published in the July issue of Evolution and Human Behaviour, the study investigated evidence of parental sexual imprinting, the sexual preference for individuals possessing parental characteristics, in women. The team used facial measurements to give a clear view of how fathers' facial features relate directly to the features of faces their daughters find attractive.

The study helps shed further light on how we choose partners and the impact of a parent's role in this process, which until recently researchers believed to be a passive one. It adds to growing theories that suggest sexual imprinting is an active process which involves the relationship between the child and the adult upon whom they imprint. This reveals the importance of parental relationships in partner selection, which could move studies in areas like evolutionary biology, fertility and genetics a step forward and offer new insights in areas such as relationship counselling and psychology.

Author Dr Lynda Boothroyd of Durham University explains: "While previous research has suggested this to be the case, these controlled results show for certain that the quality of a daughter's relationship with her father has an impact on whom she finds attractive. It shows our human brains don't simply build prototypes of the ideal face based on those we see around us, rather they build them based on those to whom we have a strongly positive relationship. We can now say that daughters who have very positive childhood relationships with their fathers choose men with similar central facial characteristics to their fathers."

Well known "daddies' girls" such as Nigella Lawson and Zoe Ball back up these findings. A comparison of pictures of Charles Saatchi with Nigel Lawson and Norman Cook with Johnny Ball reveals some close correlations, especially in the central facial area, including the nose, chin and eyes.

The study used a sample of 49 Polish eldest daughters. Each chose the most attractive face from 15 distinct faces, whose ears, hair, neck, shoulders and clothing were not visible, removing any external influences which could potentially skew results. The male stimuli's facial measurements were taken and compared with each daughter's father's measurements, so that the researchers knew which faces correlated most closely with the fathers' faces.

The daughters were asked to rate their paternal relationships looking at areas such as how much a father engaged in bringing up his daughter, how much leisure time he spent with her and how much emotional investment she received from him. These scores then made up an overall "positivity" score.

Study of protein folds offers insight into metabolic evolution

Sun, 20 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers at the University of Illinois have constructed the first global family tree of metabolic protein architecture. Their approach offers a new window on the evolutionary history of metabolism.

The study appears this week in the online edition of the Proceedings of the National Academy of Sciences.

Their work relies on established techniques of phylogenetic analysis developed in the past decade to plot the evolution of genes and organisms but which have never before been used to work out the evolutionary history of protein architecture across biological networks.

We are interested in how structure evolves, not how organisms evolve, said professor of crop sciences Gustavo Caetano-Anoll's, principal researcher on the study, which was co-written by graduate student Hee Shin Kim and emeritus professor of cell and developmental biology Jay E. Mittenthal. We are using the techniques of phylogenetic analysis that systematicists used to build the tree of life, and we are applying it to a biochemical problem, a systems biology problem.

To get at the roots of protein evolution, the researchers examined metabolic proteins at the level of their component structures: easily recognizable folds in the proteins that have known enzymatic activities. These protein domains catalyze a range of functions, breaking down or combining metabolites, small molecules that include the building blocks of all life.

Their findings relied on a fundamental assumption: that the most widely utilized protein folds (they looked at proteins in more than 200 species) were also the most ancient.

Protein architecture has preserved ancient structural designs as fossils of ancient biochemistries, the authors wrote.

The team used data from two international compilations of genetic and proteomic information: the metabolic pathways database of the Kyoto Encyclopedia of Genes and Genomes, and the Structural Classification of Proteins database. They combined these two data sets with phylogenetic reconstructions, or family trees, of protein fold architectures in metabolism.

Is Sex Necessary for Evolution?

Mon, 26 Mar 2007 07:58:49 PST

( from http://www.rxpgnews.com ) If you own a birdbath, chances are you are hosting one of evolutionary biology's most puzzling enigmas: bdelloid rotifers. These microscopic invertebrates -widely distributed in mosses, creeks, ponds, and other freshwater repositories -abandoned sex perhaps 100 million years ago, yet have apparently diverged into nearly 400 species. Bdelloids (the "b" is silent) reproduce through parthenogenesis, which generates offspring with essentially the same genome as their mother from unfertilized eggs. Biologists have yet to find males, hermaphrodites, or any trace of meiosis- the process that creates sex cells - challenging the long-held assumption that evolutionary success requires genetic exchange.

The genetic variation created by meiosis and fertilization, theory holds, bolsters a species's capacity to weather shifting environmental conditions or resist rapidly evolving parasites. (During meiosis, the genome splits in two, and chromosome pairs swap bits of their DNA; during fertilization, the sex cells fuse to restore the complete genome.) Many multicellular eukaryotes pass through a sexual and asexual phase in their life cycle. But eschewing sex altogether, Ã la bdelloids, is not theoretically consistent with a long-lived evolutionary life span or extensive species diversification.

In a new study, Diego Fontaneto, Timothy Barraclough, and colleagues developed new statistical techniques for combined molecular and morphological analyses of rotifers to test the notion that species diversification requires sex. The researchers show that, despite an ancient aversion for interbreeding, bdelloids display evolutionary patterns similar to those seen in sexually reproducing taxa. How they have avoided the pitfalls of a lifestyle widely regarded as evolutionary suicide remains an open question.

Bdelloids have remained such an enduring enigma in part because biologists are still debating whether species exist as true evolutionary entities. And if they do, what forces determine how they diverge? Traditional taxonomy relies on morphological differences to classify species, but it can't distinguish whether such differences reflect physical variations among a group of clones or adaptations among independently evolving populations. In the traditional view of species diversification, interbreeding promotes cohesion within a population-maintaining the species -and barriers to interbreeding (called reproduction isolation) promote species divergence. With no interbreeding to maintain cohesion, the thinking goes, asexual taxa might not diversify into distinct species.

Fontaneto et al. defined species as independently evolving, distinct populations (or units of diversity) subject to distinct evolutionary mechanisms. They predicted that if factors other than interbreeding - such as niche specialization -controlled species cohesion and divergence, then asexual taxa should diverge along the same lines as sexually reproducing organisms. And if this were the case, they would expect to find genetic and morphological cohesion within independently evolving populations and divergence between them.

To detect independently evolving populations, the researchers analyzed marker genes isolated from clones of bdelloids collected from diverse habitats around the world. They constructed evolutionary trees using both mitochondrial and nuclear DNA sequences (the molecular "barcode" cox1and 28S ribosomal DNA sequences, respectively) to identify species within the samples. For the morphological analysis, they measured the size and shape of the rotifers' jaws (called trophi).

The morphological results largely fell in line with traditional taxonomic classifications for most bdelloid species. And species identified as related on the DNA trees typically had similar morphology. The correspondence between the molecular and morphological results suggests that the majority of traditionally identified bdelloid species are what's known as monophyletic- individuals in the same species assort together on the evolutionary tree and share a common ancestor. Only two of these traditional, monophyletic species showed significant variation in trophi size or shape among the populations; both also showed significant divergence in the DNA trees.

Using statistical models to determine the likely origin of the observed DNA tree branching patterns, the researchers show that these distinct monophyletic genetic clusters represent independently evolving entities (rather than variations within a single asexual population). But what caused them to evolve independently? Are they geographically isolated populations that evolved under neutral selection, or did they evolve into ecologically discrete species as a result of divergent selection pressures on trophi morphology?

Scanning electron micrographs showing morphological variation of bdelloid rotifers and their jaws. Have these asexual animals really diversified into evolutionary species? (Image: Diego Fontaneto)

If bdelloids have experienced divergent selection, the researchers explain, they would expect to see high variation in trophi traits between species, and low intraspecies variation (compared to neutral changes). And that's what they found -bdelloids have experienced divergent selection on trophi size (and to a lesser degree, on trophi shape) at the species level.

Altogether, these results show that the asexual bdelloids have indeed experienced divergent selection on feeding morphology, most likely as they adapted to different food sources found in different niches. By showing that asexual organisms have diverged into "independently evolving and distinct entities," the researchers argue, this study "refutes the idea that sex is necessary for diversification into evolutionary species." They hope others use their approach to study mechanisms underlying species divergence in sexual taxa to clarify the hazy nature of species and biological diversity.

Indians make one major human race: US study

Wed, 27 Dec 2006 17:01:09 PST

( from http://www.rxpgnews.com ) Washington, Dec 27 - Indians make up one of the major human ancestry groups, with relatively little genetic differentiation among the people from different parts of the country, according to a new US study.

Although the study used participants that may not reflect a random sample from India, these results still suggest that the frequencies of many genetic variants are distinctive in India compared to other parts of the world, an Indian American scientist who led the study said.

'We were struck both by the low level of diversity amongst people spanning such a large geographical region, and by the fact that people of the Indian sub-continent constituted a distinct group when compared to populations from other parts of the world,' said Pragna I. Patel.

The study led by Patel, professor of biochemistry and molecular biology at the Keck School of Medicine of the University of Southern California -, represents the largest study of Indian genetic variation performed to date, in terms of the total number of sites in the human genome that were surveyed.

Her group is using this study as a foundation for future studies on the genetic basis of various common diseases in Asian Indians - such as heart disease, which is highly prevalent in this population.

For their study, Patel and Noah Rosenberg, assistant professor in the department of Human Genetics at the University of Michigan, conducted genetic analysis of Indian-born individuals in the US. Their studies of 1,200 genome-wide polymorphisms collected from 432 individuals representing 15 different Indian populations, have begun to shed light on the genetic variations of the diverse population of India.

Patel took up the project as despite the fact that the people of India constitute more than one-sixth of the world's entire population, they have been underrepresented in studies related to genetic diseases.

And with the growth of modernisation, complex genetic diseases associated with urban and western lifestyles have risen to near-epidemic proportions, making genetic cataloguing and association studies of particular importance.

The research group also includes other researchers from the USC Institute for Genetic Medicine at the Keck School of Medicine, the University of Michigan, the departments of neurology and molecular and human genetics at Baylor College of Medicine in Houston, Texas, and the Centre for Medical Genetics at the Marshfield Medical Research Foundation, Marshfield, Wisconsin.

The study was funded by a Burroughs Wellcome Fund Career Award in the Biomedical Sciences -, an Alfred P. Sloan Research Fellowship - and a grant from the University of Southern California. The National Heart, Lung and Blood Institute provided additional support for genotyping.

Gendered division of labor gave modern humans advantage over Neanderthals

Mon, 04 Dec 2006 11:38:06 PST

( from http://www.rxpgnews.com ) Diversified social roles for men, women, and children may have given Homo sapiens an advantage over Neanderthals, says a new study in the December 2006 issue of Current Anthropology. The study argues that division of economic labor by sex and age emerged relatively recently in human evolutionary history and facilitated the spread of modern humans throughout Eurasia.

"The competitive advantage enjoyed by modern humans came not just from new weapons and devices but from the ways in which their economic lives were organized around the advantages of cooperation and complementary subsistence roles for men, women, and children," write Steven L. Kuhn and Mary C. Stiner (University of Arizona).

Kuhn and Stiner note that the rich archaeological record for Neanderthal diets provides little direct evidence for a reliance on subsistence foods, such as milling stones to grind nuts and seeds. Instead, Neanderthals depended on large game, a high-stakes resource, to fuel their massive body mass and high caloric intake. This lack of food diversity and the presence of healed fractures on Neanderthal skeletons—attesting to a rough-and-tumble lifestyle—suggest that female and juvenile Neanderthals participated actively in the hunt by serving as game drivers, beating bushes or cutting off escape routes.

The Middle Paleolithic Neanderthal record also lacks the artifacts commonly used to make weather-resistant clothing or artificial shelters, such as bone needles. Thus, it was the emergence of "female" roles – subsistence and skill-intensive craft – that allowed H. sapiens in ecologically diverse tropical and sub-tropical regions to take advantage of other foods and live at higher population densities.

"Earlier hominins pursued more narrowly focused economies, with women's activities more closely aligned with those of men with respect to schedule and ranging patterns," write the authors. "It is impossible to argue that [Neanderthal] females and juveniles were fulfilling the same roles—or even an equally diverse suite of economic roles—as females and juveniles in recent hunter-gatherer groups," they add.

While some degree of niche specialization between adult male and females is documented for many large-mammal species, recent humans are remarkable for cooperative economies that combine pervasive sharing and complementary roles for individuals of different ages and sexes.

Genetic variation: We're more different than we thought

Tue, 28 Nov 2006 22:40:14 PST

( from http://www.rxpgnews.com ) New research shows that at least 10 percent of genes in the human population can vary in the number of copies of DNA sequences they contain--a finding that alters current thinking that the DNA of any two humans is 99.9 percent similar in content and identity.

This discovery of the extent of genetic variation, by Howard Hughes Medical Institute (HHMI) international research scholar Stephen W. Scherer, and colleagues, is expected to change the way researchers think about genetic diseases and human evolution.

Genes usually occur in two copies, one inherited from each parent. Scherer and colleagues found approximately 2,900 genes--more than 10 percent of the genes in the human genome--with variations in the number of copies of specific DNA segments. These differences in copy number can influence gene activity and ultimately an organism's function.

To get a better picture of exactly how important this type of variation is for human evolution and disease, Scherer's team compared DNA from 270 people with Asian, African, or European ancestry that had been compiled in the HapMap collection and previously used to map the single nucleotide changes in the human genome. Scherer's team mapped the number of duplicated or deleted genes, which they call copy number variations (CNVs). They reported their findings in the November 23, 2006, issue of the journal Nature.

Scherer, a geneticist at the Hospital for Sick Children and the University of Toronto, and colleagues searched for CNVs using microarray-based genome scanning techniques capable of finding changes at least 1,000 bases (nucleotides) long. A base, or nucleotide, is the fundamental building block of DNA. They found an average of 70 CNVs averaging 250,000 nucleotides in size in each DNA sample. In all, the group identified 1,447 different CNVs that collectively covered about 12 percent of the human genome and six to 19 percent of any given chromosome--far more widespread than previously thought.

Not only were the changes common, they also were large. "We'd find missing pieces of DNA, some a million or so nucleotides long," Scherer said. "We used to think that if you had big changes like this, then they must be involved in disease. But we are showing that we can all have these changes."

The group found nearly 16 percent of known disease-related genes in the CNVs, including genes involved in rare genetic disorders such as DiGeorge, Angelman, Williams-Beuren, and Prader-Willi syndromes, as well as those linked with schizophrenia, cataracts, spinal muscular atrophy, and atherosclerosis.

In related research published November 23, 2006, in an advance online publication in Nature Genetics, Scherer and colleagues also compared the two human genome maps--one assembled by Celera Genomics, Inc., and one from the public Human Genome Project. They found thousands of differences.

"Other people have [compared the two human genome sequences]," Scherer said, "but they found so many differences that they mostly attributed the results to error. They couldn't believe the alterations they found might be variants between the sources of DNA being analyzed."

A lot of the differences are indeed real, and they raise a red flag, he said.

Personalized genome sequencing--for individualized diagnosis, treatment, and prevention of disease--is not far off, Scherer pointed out. "The idea [behind comparing the human genome sequences] was to come up with a good understanding of what we're going to get when we do [personalized sequencing]," he explained. "This paper helps us think about how complex it will be."

In a "News and Views" article in the same issue of Nature, HHMI professor Huntington F. Willard writes, "the stage is set for global studies to explore anew…the clinical significance of human variation." Willard is director of the Institute for Genome and Science Policy at Duke University.

To fully extract meaningful data using the human genome maps, researchers must know what's missing and how much variation exists, Scherer said. "Our computer algorithms are smart, but it is hard to find something if it is not there in the reference you are comparing against."

In fact, Scherer's group found some 30 million nucleotides that are seemingly not yet represented at all, or in different copy numbers or orientations, when comparing the Celera assembly to the public human genome sequence. The entire human genome is thought to contain about 3 billion nucleotides.

The discovery of an abundance of DNA variation puts a whole new spin on the study of genetic disease. Most research has focused on small alterations, called single nucleotide polymorphisms (SNPs). It may be, said Scherer, that some diseases are caused by copy number variations rather than SNPs. In fact, recent research has already linked such variations to kidney disease, Parkinson's disease, Alzheimer's disease, and AIDS susceptibility.

The discovery also provides a new outlook on evolution.

"Until now, our focus has been on examining evolution through either small SNP changes or larger chromosomal alterations you can see under the microscope, because that's what we could detect," Scherer said. "But now there's a whole new class of mid-sized variants encompassing millions of nucleotides of DNA to consider."

This change in the way scientists think about human genetics is exciting, but it is still very early to know what all this means, said Scherer. "Though it does make you wonder, he added. "If you have 1 million fewer nucleotides than your buddy, shouldn't you get a break on your golf handicap?"

New approach will pinpoint genes linked to evolution of human brain

Tue, 14 Nov 2006 17:45:37 PST

( from http://www.rxpgnews.com )

Six million years ago, chimpanzees and humans diverged from a common ancestor and evolved into unique species. Now UCLA scientists have identified a new way to pinpoint the genes that separate us from our closest living relative and make us uniquely human.

"We share more than 95 percent of our genetic blueprint with chimps," explained Dr. Daniel Geschwind, principal investigator and Gordon and Virginia MacDonald Distinguished Professor of Human Genetics at the David Geffen School of Medicine. "What sets us apart from chimps are our brains: homo sapiens means 'the knowing man.'

"During evolution, changes in some genes altered how the human brain functions," he added. "Our research has identified an entirely new way to identify those genes in the small portion of our DNA that differs from the chimpanzee's."

By evaluating the correlated activity of thousands of genes, the UCLA team identified not just individual genes, but entire networks of interconnected genes whose expression patterns within the brains of humans varied from those in the chimpanzee.

"Genes don't operate in isolation each functions within a system of related genes," said first author Michael Oldham, UCLA genetics researcher. "If we examined each gene individually, it would be similar to reading every fifth word in a paragraph you don't get to see how each word relates to the other. So instead we used a systems biology approach to study each gene within its context."

The scientists identified networks of genes that correspond to specific brain regions. When they compared these networks between humans and chimps, they found that the gene networks differed the most widely in the cerebral cortex -- the brain's most highly evolved region, which is three times larger in humans than chimps.

Secondly, the researchers discovered that many of the genes that play a central role in cerebral cortex networks in humans, but not in the chimpanzee, also show significant changes at the DNA level.

"When we see alterations in a gene network that correspond to functional changes in the genome, it implies that these differences are very meaningful," said Oldham. "This finding supports the theory that variations in the DNA sequence contributed to human evolution."

Relying on a new analytical approach developed by corresponding author Steve Horvath, UCLA associate professor of human genetics and biostatistics, the UCLA team used data from DNA microarrays vast collections of tiny DNA spots -- to map the activity of virtually every gene in the genome simultaneously. By comparing gene activity in different areas of the brain, the team identified gene networks that correlated to specific brain regions. Then they compared the strength of these correlations between humans and chimps.

Many of the human-specific gene networks identified by the scientists related to learning, brain cell activity and energy metabolism.

"If you view the brain as the body's engine, our findings suggest that the human brain fires like a 12-cylinder engine, while the chimp brain works more like a 6-cylinder engine," explained Geschwind. "It's possible that our genes adapted to allow our brains to increase in size, operate at different speeds, metabolize energy faster and enhance connections between brain cells across different brain regions."

New genetic analysis forces re-draw of insect family tree

Sun, 29 Oct 2006 22:25:37 PST

( from http://www.rxpgnews.com ) The family tree covering almost half the animal species on the planet has been re-drawn following a genetic analysis which has revealed new relationships between four major groups of insects.

Scientists have found that flies and moths are most closely related to beetles and more distantly related to bees and wasps, contrary to previous theory.

The results are based on an analysis of the same 185 genes found in the genomes of eight different insect families, which together represent 45 per cent of all known animal species.

This enabled the international group of scientists to work out the evolutionary relationships between the insects based on changes and mutations within those genes.

Previously scientists had assumed that flies and moths were most closely related to bees and wasps, with beetles more distantly related to these groups.

This new family arrangement also brings the different species of social insects, such as termites and bees, closer together - suggesting that the ability of insects to cooperate in social groupings may have evolved just once, rather than independently in several different species.

About half of all animal species belong to just four groups of insects but, surprisingly, we never knew for sure how they are related to each other, said Dr Martin Lercher from the University of Bath, who lead the research.

While there was never unequivocal evidence for it, scientists believed for a long time that, based on morphology, flies and moths were most closely related to bees, with beetles more distantly related to these three groups.

By comparing genetic information from 185 genes that were sequenced in species from all of these groups, we found that in fact flies and moths are most closely related to beetles, and more distantly related to bees.

This sheds new light on a large number of evolutionary questions, as a correct understanding of the evolutionary relationships is fundamental to any interpretation of similarities or differences among species.

For example, social colonies are common among bees and wasps and their relatives, ants, as well as among more distantly related insects, such as termites and aphids.

That beetles don't show this tendency, known as eusociality, has been interpreted as a sign that eusociality has evolved several times independently.

Now that we know that bees, wasps and ants are in fact the closest relatives to the more distantly related (or basal) species, it appears more likely that the genetic basis for eusociality may have evolved only once, and was lost in the common ancestor of beetles, moths, and flies.

The researchers used the genomes of six different insects from the holometabolous group of insects (insects which undergo complete metamorphosis): fruit fly (Drosophila melanogaster), mosquito (Anopheles gambiae), silk moth (Bombyx mori), flour beetle (Tribolium castaneum), honey bee (Apis mellifera) and sibling parasitic wasp species (Nasonia vitripennis and Nasonia giraulti).

These insects represent the four major orders of holometabolous insects, beetles (Coleoptera), moths (Lepidoptera), flies (Diptera) and bees and wasps (Hymenoptera), which together represent 45 per cent of the animal species on earth.

They also included one orthopteran (the grasshopper Locusta migratoria) and one hemipteran (the pea aphid Acyrthosiphon pisum), both of which are uncontested out-groups to the holometabolous insects.

Giant insects might reign if only there was more oxygen in the air

Thu, 12 Oct 2006 04:51:37 PST

( from http://www.rxpgnews.com ) The delicate lady bug in your garden could be frighteningly large if only there was a greater concentration of oxygen in the air, a new study concludes. The study adds support to the theory that some insects were much larger during the late Paleozoic period because they had a much richer oxygen supply, said the study's lead author Alexander Kaiser.

The study, "No giants today: tracheal oxygen supply to the legs limits beetle size,'' will be presented Oct. 10 and 11 at Comparative Physiology 2006: Integrating Diversity. The conference will be held Oct. 8-11 in Virginia Beach. The research was carried out by Alexander Kaiser and Michael C. Quinlan of Midwestern University, Glendale, Arizona; J. Jake Socha and Wah-Keat Lee, Argonne National Laboratory, Argonne, IL; and Jaco Klok and Jon F. Harrison, Arizona State University, Tempe, AZ. Harrison is the principal investigator.

The Paleozoic period, about 300 million years ago, was a time of huge and abundant plant life and rather large insects -- dragonflies had two-and-a-half-foot wing spans, for example. The air's oxygen content was 35% during this period, compared to the 21% we breathe now, Kaiser said. Researchers have speculated that the higher oxygen concentration allowed insects to grow much bigger.

Tubes carry oxygen

First, a bit of background: Insects don't breathe like we do and don't use blood to transport oxygen. They take in oxygen and expel carbon dioxide through holes in their bodies called spiracles. These holes connect to branching and interconnecting tubes, called tracheae, Kaiser explained.

Whereas humans have one trachea, insects have a whole tracheal system that transports oxygen to all areas of their bodies and removes carbon dioxide. As the insect grows, tracheal tubes get longer to reach central tissue, and get wider or more numerous to meet the additional oxygen demands of a larger body.

Insects can limit oxygen flow by closing their spiracles. In fact, one reason insects are so hardy is that they can close their spiracles and live off the oxygen they already have in their tracheae. Kaiser recalled a caterpillar that fell into a bucket of water in his lab. When the creature was discovered the next day, lab workers thought it had drowned. But when they removed its apparently lifeless little body from the water, they were surprised to see it crawl away.

Tracheae grow disproportionately

This experiment was designed to find out:

* how much room the tracheal system takes up in the bodies of different-sized beetles
* whether tracheal dimensions increase proportionately as the beetles get larger
* whether there is a limit to the size a beetle could grow in the current atmosphere

The researchers used x-ray images to compare the tracheal dimensions of four species of beetles, ranging in size from 3mm (Tribolium castaneum, about one-tenth of an inch) to about 3.5 cm (Eleodes obscura, about 1.5 inches). Beetles were not in existence during the Paleozoic period, but Kaiser's team used the insect because they are much easier to maintain in the laboratory than dragonflies, which are quite difficult.

The study found that the tracheae of the larger beetles take up a greater proportion of their bodies, about 20% more, than the increase in their body size would predict, Kaiser said. This is because the tracheal system is not only becoming longer to reach longer limbs, but the tubes increase in diameter or number to take in more air to handle the additional oxygen demands.

The disproportionate increase in tracheal size reaches a critical point at the opening where the leg and body meet, the researchers found. This opening can get only so big, and limits the size of the trachea that runs through it. When tracheal size is limited, so is oxygen supply and so is growth, Kaiser explained.

Using the disproportional increases they observed among the beetles, the researchers calculated that beetles could not grow larger than about 15 centimeters. And this is the size of the largest beetle known: the Titanic longhorn beetle, Titanus giganteus, from South America, which grows 15-17 cm, Kaiser said.

And why wouldn't the opening between the body and the leg limit insect size in the Paleozoic era, too? After all, dragonflies and some other insects back then had the same body architecture, but they were much bigger.

It is because when the oxygen concentration in the atmosphere is high, the insect needs smaller quantities of air to meet its oxygen demands. The tracheal diameter can be narrower and still deliver enough oxygen for a much larger insect, Kaiser concluded.

Infection Status Drives Interspecies Mating Choices in Fruit Fly Females

Wed, 11 Oct 2006 05:24:37 PST

( from http://www.rxpgnews.com ) Hybridization is a constant possibility for two closely related species. Geographic isolation prevents interbreeding in some cases, but when the range of the two overlap, other mechanisms must come into play if they are to remain genetically distinct. Behavioral isolation is one such mechanism. If members of each group preferentially mate with their own kind, the two species can remain distinct even while residing together. Over time, such isolating behaviors may become more pronounced, and the genes governing them more widespread, a phenomenon termed reinforcement.

In evolutionary theory, reinforcement has typically been thought to act symmetrically on the two species. In a new study, however, John Jaenike and colleagues show that bacterial infection of one Drosophila species, but not another, and the resulting differences in hybrid viability, may account for highly asymmetrical reinforcement occurring in the two.

Wolbachia is a bacterium that infects many insect species, where it lives within the cells of the host, especially the ova and testes, and is transmitted from infected females to their offspring. Wolbachia infects virtually all members of the fruit fly species Drosophila recens, but not members of the closely related D. subquinaria. When an infected male D. recens mates with an uninfected female D. subquinaria, most offspring die in a process called cytoplasmic incompatibility. In contrast, however, when an infected female D. recens mates with an uninfected male D. subquinaria, the offspring are viable, and the hybrid females are fertile (the males are sterile, a typical result from cross-species hybridization).

Geographical distributions of Drosophila subquinaria (black) and D. recens (gray), showing allopatric populations of D. subquinaria in the west and D. recens in the east, and sympatric populations in central Canada.

To explore the effect of this difference on reinforcement, the authors began by establishing that the two species do indeed overlap in part of their range (a condition called sympatry), in central Canada, while maintaining separate populations elsewhere (allopatry). In the laboratory, uninfected D. subquinaria females from the region of sympatry never mated with D. recens males, while those from the region of allopatry did. They found no such pattern for infected D. recens females; instead, females from both regions were likely to mate with uninfected D. subquinaria males when placed together. The same discrimination or its lack was seen whether the females were presented with only one type of male (no choice conditions), or with males from both species, as might occur in the wild.

These mate-choice experiments illuminated two important phenomena. First, the most discriminating D. subquinaria females were those from populations living side-by-side with infected D. recens males. This makes sense, the authors suggest, given that less-choosy females that engage in such matings would leave few offspring, since almost all die off. Indeed, as the authors discovered, sympatric D. subquinaria females appeared to be so averse to mating outside their group that they also avoided mating with D. subquinaria males that came from the allopatric region. In contrast, allopatric D. subquinaria females, which have not been subjected to the same selective pressure, are not as discriminating. Second, D. recens females did not avoid interspecific matings nearly as strongly, since they also are not under the same selective pressure. Thus, the reinforcement processthe increase in mate discriminationis highly asymmetric between the two species.

Finally, the authors asked whether the behavioral differences between sympatric and allopatric D. subquinaria females correlated with larger-scale genetic differences between the groups. They found it did not, and that overall there is considerable gene flow between the populations. This indicates that the differences in mate choice are likely the result of natural selection acting within the region of sympatry, rather than simple genetic isolation of the two populations. Interestingly, the reproductive isolation of the two D. subquinaria populations has been driven not by factors intrinsic to them, but by infection of entirely different species. It is possible that this isolation will ultimately lead to speciation within D. subquinaria, although the current high degree of similarity and existence of gene flow may suggest otherwise.

Mother birds give a nutritional leg up to chicks with unattractive fathers

Tue, 26 Sep 2006 22:37:37 PST

( from http://www.rxpgnews.com ) Mother birds deposit variable amounts of antioxidants into egg yolks, and it has long been theorized that females invest more in offspring sired by better quality males. However, a study from the November/December 2006 issue of Physiological and Biochemical Zoology shows that even ugly birds get their day. Providing new insight into the strategic basis behind resource allocation in eggs, the researchers found that female house finches deposit significantly more antioxidants, which protect the embryo during the developmental process, into eggs sired by less attractive fathers.

"For female birds, an important aspect of parental investment is the resources allocated to eggs," writes Dr. Kristen J. Navara (Auburn University and Ohio State University) and her coauthors. "The resources available to any female for reproduction and self-maintenance will be finite and she will inevitably be faced with decisions regarding how much resource to invest in each egg in each clutch she lays."

Male house finches display nutrition-linked plumage ranging in color from bright red to drab yellow. The researchers found that eggs sired by unattractive males (those with less brilliant feathers) had more total antioxidants, including 2.5 times the vitamin E levels, than eggs sired by males with redder, more saturated plumage. Thus, they explain, the deposition of more nutrients could represent compensation for the disadvantages experienced by an offspring from a lower quality male, allowing females to supersede limitations of a suboptimal pairing on her own reproductive success.

"For house finches, a species in which individuals are short-lived [and] present a high risk of death, a focus on the immediate reproductive attempts may be the only viable strategy," write the researchers. "By depositing antioxidants in a compensatory manner, females can maximize the reproductive output from the current nesting effort."

Mammals Evolve Faster on Islands!

Wed, 13 Sep 2006 03:47:37 PST

( from http://www.rxpgnews.com ) The notion of islands as natural testbeds for evolutionary study is nearly as old as the theory of evolution itself. The restricted scale, isolation, and sharp boundaries of islands create unique selective pressures, often to dramatic effect. Following whatâs known as the âisland rule,â small animals evolve into outsize versions of their continental counterparts while large animals shrink. Once restricted to islands, small animals often lacked predators and the competition between species that constrained the growth of their relatives on the mainland. Large mammals, on the other hand, no longer had access to vast grasslands and other abundant food sources and grew smaller to survive. Giant tortoises and iguanas still inhabit the GalÃ¡pagos and a few other remote islands today, but only fossils remain of the dwarf hippopotami, elephants, and deer that once lived on islands in Indonesia, the Mediterranean, and the Pacific Ocean.

The fossil record suggests that these size changes (as well as other morphological changes) occur rapidly after species become isolated on islands, but this assumption has never been empirically examined in a systematic manner. In a new study, Virginie Millien puts this longstanding hypothesis to the test by analyzing the fossil record and data from living species. Comparing the rates of evolutionary change between island and mainland populations for 88 species at intervals ranging from 21 years to 12 million years, Millien confirmed that island species undergo accelerated evolutionary changes over relatively short time frames, between decades and several thousand years. (One can imagine rats of horror movie proportions if such rates persisted for millions of years.)

Giant tortoises at the Darwin Station on Isla Santa Cruz in the Galápagos Islands. (Photo: Catriona MacCallum)

Measuring rates of evolutionary change has proven difficult because the fossil record rarely captures every morphological shift in a lineage, precise dating isnât always possible, and itâs often not clear when the ancestral form first appeared on the island. To get a robust sample of island and mainland mammalian species, Millien collected data from text, figures, and tables in an extensive survey of the published literature. From these datasets, she calculated a total of 826 evolutionary rates for 170 populations representing the 88 species. (Rates of evolutionary change are measured in units called, appropriately enough, âdarwins.â)

Evolution rates, she found, decreased over time intervals for both island and mainland species, with a slower rate of decrease for island species. The differences in evolutionary rates between island and mainland pairs also decreased over time, becoming statistically insignificant for intervals over 45,000 years. Overall, island species evolved faster than mainland speciesâa phenomenon that was most pronounced for intervals between 21 years through 20,000 years.

Island evolution theory predicts that the most extreme effects of isolation will be seen on the smallest, most far-flung islands. In keeping with theory, Millien found that evolutionary rates for different populations of the same species varied with island locale. Thus, the rate of evolution does not appear to be an evolutionarily conserved trait, like metabolic rate or whiskers.

Because rodents make up nearly half of the worldâs mammalian speciesâand over 70% of taxa on some islands in this studyâMillien repeated her analysis on a subset of the data with equal numbers of rodent and non-rodent taxa. The overrepresentation of rodents had no effect on the results, which still revealed significant differences between island and mainland evolution rates for the same species or populations.

The finding that mammals evolve faster on islands, Millien argues, comports with the island evolution theory prediction that mammals respond to their new island homes with rapid morphological and size adaptations. The brisk pace of these changes may explain why the fossil record harbors few examples of intermediate forms between the mainland ancestor and island descendant. Millienâs results also conform with the hypothesis that evolution rates for island species slow down after the initial period of accelerated change, approaching rates on the mainland.

If island species can evolve quickly, Millien argues, it stands to reason that mainland species retain a similar capacity. As habitat destruction continues to pose the number one threat to biodiversity, many mainland habitats are beginning to resemble islands, with isolated pockets of wildlife separated by degraded or developed lands. Thus, island species may serve as a model for understanding how mainland species will adapt to the rapidly changing environmental conditions brought on by habitat destruction and global warming. It appears that some mainland species are already responding like island species: a 1989 study followed the island rule in linking fragmented habitat to body size changes in 25 European mammals over the past 200 years. How long animals can continue to evolve in the face of these changes, however, remains to be seen.

A Bacterial Protein Puts a New Twist on DNA Transcription

Wed, 16 Aug 2006 09:15:37 PST

( from http://www.rxpgnews.com ) For organisms to adapt, develop, and simply live, they must regulate hundreds to thousands of genes, making fine-tuned, precisely timed adjustments to produce the specific complement of proteins required for the occasion. For bacteria, this task falls largely to proteins called sigma factors. These small proteins associate with RNA polymerase, the enzyme that mediates gene transcription, to form a complex called the holoenzyme. The holoenzyme, guided by the sigma factor, recognizes promoter regions, which are specific DNA sequences that precede protein-coding sequences and mark the transcription start site. Sigma factors also contribute to transcription by facilitating DNA strand separation, which must occur before RNA polymerase can begin copying the DNA code. Once transcription begins, the sigma factor disengages from the RNA polymerase, becoming available for new joint ventures with different RNA polymerases.

A single sigma factor can control the expression of hundreds of genes through these partnerships, carrying out everything from basic metabolic activities to physiological responses to environmental stress (which, for bacteria, might include antibiotic therapy). Knowing how sigma factors bind to DNA is an important step in understanding how they mediate their cosmopolitan regulatory duties. Structural studies provide important clues to the nature and function of associations between sigma factors and DNA. In a new study, William Lane and Seth Darst used structural analysis techniques to determine the detailed shape of one type of sigma factor. They show that it binds to short DNA sequences using a molecular recognition method that has not been seen before in sigma factors.

Sigma factors come in two structurally unrelated families: sigma 54 and sigma 70. The sigma 54 family is associated with a diverse range of metabolic processes. The much larger sigma 70 family encompasses four groups: the Group I primary sigma factors facilitate metabolic and growth processes; the Group IIIV alternative sigma factors mediate specialized processes like sporulation and the environmental stress response. The sigma 70-type sigma factors recruit the RNA polymerase holoenzyme to bipartite promoter sequences, comprising conserved sequence elements centered about 10 and 35 base pairs upstream of the transcription start site. These so-called 10 and 35 elements are recognized by distinct structural domains of the sigma factor. Structures of one of the most studied sigma factors, a primary sigma factor called sigma-A, have been solved in previous studies. Here, Lane and Darst analyzed the 35-element-binding domain (domain 4) of an alternative Group IV sigma factor found in Escherichia coli, called sigma E4. Group IV sigma factors comprise the largest and most diverse set of sigma factors.

Both sigma-A4 and sigma-E4 allow RNA polymerase to bind to the 35 promoter element, but in each case the sequence is very different. In the case of sigma-E4, the sequence is GGAACTT (and others that resemble it). Previous studies showed that sigma-A4 recognizes its consensus sequence, TTGACA, through direct interactions with these six nucleotide bases. It was tempting to assume that sigma-E4 would operate in a similar manner, since the two sigma factors are similar in structure.

But, using X-ray crystallography, Lane and Darst showed that sigma-E4 binds its consensus sequence using a more subtle method. By determining the structure of the sigma factor bound to its consensus sequence, they found that sigma-E4 doesnt recognize the identity of the sequences per se but the shape of the DNA helix at those sequences. While one region of the sigma factor sits deep within a groove along the double helixs side, another region holds the promoter 35 sequence straight. The AA in the center of sigma-E4s consensus sequence, the researchers believe, is required for the DNA to assume this shape.

Because evolution has conserved the site in these proteins that sits alongside the AA of the consensus sequence, Lane and Darst propose that this method of recognizing 35 promoter sequences may be common across the Group IV sigma factors. With further studies of the structures of sigma factors and their means of recognizing specific promotersand thus activating specific genesresearchers can better predict the full complement of genes a given promoter will regulate, and in turn gain insight into the diverse physiological responses they help mediate.

Why Does Sex Exist?

Mon, 07 Aug 2006 13:50:37 PST

( from http://www.rxpgnews.com ) Why does sex exist? A long-popular view holds that sexual reproduction creates new gene combinations that help the next generation resist rapidly co-evolving parasites. Each species constantly changes to achieve the same resultevolutionary advantageprompting evolutionary biologists to dub this hypothesis the Red Queen (who tells Alice in Through the Looking Glass it takes all the running you can do, to keep in the same place).

Recent theoretical studies have challenged the generality of the Red Queen hypothesis, suggesting that even though parasites can exert selection pressures that favor sex under some conditions, more often they select against it. They do this, the studies found, by selecting against genes that increase the degree of genetic mixing. And now, Aneil Agrawal has come to the Red Queen's rescue with his own theoretical analysis. While the recent models assumed that hostparasite encounters are random, Agrawal shows that when nonrandom interactions are assumedso that a host is more likely to acquire parasites from its motherselective pressures from parasites are much more likely to favor sex.

In theoretical models that assume random hostparasite interactions, the host's fitness depends only on its own genetic makeup (or genotype), a scenario called genotypic selection. If the host stands a reasonable chance (above what would be expected to occur randomly) of contracting infection from its mother, host fitness will also depend on the host's genetic similarity to its mother (called similarity selection).

Agrawal's model allows an individual host's fitness to depend both on its own genotype and on its similarity to its mother's genotype. This framework can describe selection by parasites that are encountered randomly or are transmitted by the mother. Risk of maternal transmission will be high when parasites pass directly from mother to offspring through her eggs. The likelihood of transmission will diminish if offspring acquire infection after dispersal. Offspring that have the same genotype as their mother will be more susceptible to parasites from their mother than those with different genes. Thus, Agrawal explains, to the extent that maternal transmission occurs, hosts will be subject to both genotypic and similarity selection.

If the Red Queen hypothesis is true, and hostparasite co-evolution underlies the evolution and maintenance of sex, then these species interactions should create links between gene variants (or alleles) that enhance genetic mixing and alleles related to fitness. (The alleles that influence genetic mixing are called modifier alleles, because they influence the degree of investment into sexual rather than asexual reproduction.)

The Red Queen hypothesis posits that sex allows hosts to evade co-evolving parasites. (Photo: William F. Duffy)

Agrawal first determined how a modifier allele evolves under different scenarios involving genotypic and similarity selection. He then evaluated the extent of genotypic and similarity selection produced by hostparasite co-evolution, and showed how the likelihood of maternal transmission affects whether parasites select for or against sex. He found that even though similarity selection has a much weaker effect than genotypic selection on fitness, it can exert a powerful force on the evolution of modifier alleles (and thus sex). Even a small chance of maternal transmission can lead to parasite selection for sex, Agrawal explains, because similarity selection affects genetic associations between mother and offspring, which tend to be strong (as opposed to genetic associations within offspring, which tend to be weaker).

Previous models have shown that sex is favored under very limited conditions in large, randomly breeding populations because genetic mixing tends to break down beneficial gene combinations produced by selection, which presumably enhance fitness. By incorporating the fitness effects of similarity selection, Agrawal could examine similarity selection's potential impacts on the evolution of modifier alleles independent of its fitness effectsand discover that parasites are much more likely to favor sex. The model predicts that this is most likely to occur when parasites are directly transmitted from mother to offspring, virulence is low, and infection rates are high (otherwise, too few offspring are produced by infected mothers).

While Agrawal doesn't argue that parasites fully explain why sex evolved, his results show that accounting for real-world transmission scenarios puts the ball squarely back in the Red Queen's court. Researchers can use his model to study the evolution of sex under a wide range of scenarios, such as when individual fitness depends on kin or other social groups.

Pseudogenes Research Reinforces Theory of Evolution

Wed, 02 Aug 2006 11:53:37 PST

( from http://www.rxpgnews.com ) Scientists led by a Childrens Hospital of Pittsburgh geneticist have found new evidence that a category of genes known as pseudogenes serve no function, an important finding that bolsters the theory of evolution.

There are approximately 20,000 pseudogenes in the human and other mammalian genomes. In recent years, there has been growing discussion about the nature of these pseudogenes. The issue centers on whether pseudogenes are functional or merely evolutionary relics with no function. It was long believed by geneticists that they were relics, until basic science research published in 2003 found a mouse pseudogene located within the Makorin family of genes that did have a function, namely to cause polycystic kidney disease and a bone disease known as osteogenesis imperfecta.

This finding, discovered in a mouse model, was hailed by proponents of Intelligent Design (ID). According to the Intelligent Design Network, the premise of intelligent design holds that certain features of the universe and of living things are best explained by an intelligent cause rather than an undirected process such as natural selection. ID is thus a disagreement with the core scientific basis of evolutionary theory.

However, researchers at Childrens and the Wadsworth Center in New York, including first author Todd A. Gray, PhD, have found scientific evidence that contradicts this finding. The pseudogene in question Mkrn1-p1 indeed is not the cause of those diseases, according to senior author Robert D. Nicholls, DPhil, director of the Birth Defects Laboratories at Childrens. Instead, according to Dr. Nicholls, it merely is an inactive copy of a gene, an evolutionary relic as previously believed.

Discussion over evolution and Intelligent Design really has centered on whether pseudogenes, sometimes called junk DNA, have a function or not. The suggestion is that an Intelligent Designer would not make junk DNA, so if a pseudogene does have a function, this is claimed to support the idea of an Intelligent Designer, Dr. Nicholls said. But there is no evidence that any of the 20,000 pseudogenes are functional. Our research proves this Makorin pseudogene does not have a function. It has continued to mutate over its short life of a few million years, a fact that supports evolution, and eventually will be discarded from the mouse genome.

But the most important implication of this research from a patient perspective is that scientists now must go back to the beginning in terms of discovering the genetic mechanism that causes polycystic kidney disease and osteogenesis imperfecta in the mouse model, according to Dr. Nicholls.

Non-human primates may be linchpin in evolution of language

Mon, 24 Jul 2006 19:32:37 PST

( from http://www.rxpgnews.com ) When contemplating the coos and screams of a fellow member of its species, the rhesus monkey, or macaque, makes use of brain regions that correspond to the two principal language centers in the human brain, according to research conducted by scientists at the National Institute on Deafness and Other Communication Disorders (NIDCD) and the National Institute of Mental Health (NIMH), two of the National Institutes of Health. The finding, published July 23 in the advance online issue of Nature Neuroscience, bolsters the hypothesis that a shared ancestor to humans and present-day non-human primates may have possessed the key neural mechanisms upon which language was built. Principal collaborators on the study are Allen Braun, M.D., chief of NIDCD's Language Section, Alex Martin, Ph.D., chief of NIMH's Cognitive Neuropsychology Section, and Ricardo Gil-da-Costa, Gulbenkian Science Institute, Oeiras, Portugal, who conducted the study during a three-year joint appointment at the NIDCD and NIMH.

"This intriguing finding brings us closer to understanding the point at which the building blocks of language appeared on the evolutionary timeline," says James F. Battey, Jr., M.D., Ph.D., director of the NIDCD. "While the fossil record cannot answer this question for us, we can turn to the here and now through brain imaging of living non-human primates for a glimpse into how language, or at least the neural circuitry required for language, came to be."

While non-human primates do not possess language, they are able to communicate about such things as food, identity, or danger to members of their species by way of vocalizations that are interpreted and acted upon. In humans, the two main regions of the brain that are involved in encoding this type of information in language are known as Broca's area and Wernicke's area, named for the physician-researchers who discovered them. Both areas are located along the Sylvian fissure (and are therefore referred to as perisylvian areas) with Broca's area located in the frontal lobe and Wernicke's area located behind it in the temporal and parietal lobes. Scientists once believed that Broca's area was chiefly involved in language production while Wernicke's area dealt more with comprehension, however current thinking suggests that the two areas work in tandem with one another. Although monkeys are not able to perform the mental activities required for language, their brains possess regions that are structurally similar to the perisylvian areas in humans in both hemispheres. The functional significance of such similarities, however, has been unclear up to this point.

To measure brain activity, the researchers injected water labeled with oxygen-15, a biologically safe, fast-degrading radioisotope, into the bloodstream of three adult macaques. As neural activity increases in a given region of the brain, blood and the radioactive water it carries rushes into that region. Using the brain imaging technology known as positron emission tomography (PET), researchers capture an image of the radioactive areas, thus highlighting the regions of heightened activity. In this way, brain scans were taken of the monkeys as they listened to three types of sounds: the recorded coos and screams of other rhesus monkeys, and assorted non-biological sounds, such as musical instruments and computer-synthesized sounds, which matched the vocalizations in frequency, rate, scale, and duration. For each monkey, 16 scans were recorded for each sound type and compared.

Although the coo of a monkey is acoustically very different from a high-pitched scream, the researchers found that both of these meaningful species-specific sounds elicited significantly more activity than the non-biological control stimuli in the same three regions of the macaque's brain. Moreover, these regions correspond to the key language centers in humans, with the ventral premotor cortex (PMv) corresponding to Broca's area, and the temporoparietal area (Tpt) and posterior parietal cortex (PPC) corresponding to Wernicke's area. In contrast, the non-biological sounds which were acoustically similar to the coos and screams but had no meaning for the animals elicited significantly less activity in these regions; rather, they were associated with greater activation of the brain's primary auditory areas. (The reason for this, the researchers suggest, is that these sounds were new to the monkeys and the primary auditory areas may be especially attuned to novel stimuli.)

Based on these findings, the researchers suggest that the communication centers in the brain of the last common ancestor to macaques and humans particularly those centers used for interpreting species-specific vocalizations may have been recruited during the evolution of language in humans. In the macaque, these areas may currently play a parallel, prelinguistic function, in which monkeys are able to assign meaning to species-specific sounds. In addition, in light of an earlier study published by the same group, in which species-specific vocalizations of macaques activated brain regions that process higher-order visual and emotional information, the researchers suggest that the language areas of the brain may have evolved from a much larger system used to extract meaning from socially relevant situations a system in which humans and non-human primates may share similar neural pathways.

Further studies to be conducted include investigating which regions of the non-human primate brain are activated when animals listen to meaningful auditory stimuli other than species-specific vocalizations, such as a predators' calls, sounds made by humans, or other relevant environmental stimuli. In addition, they are interested in studying the pattern of brain activation elicited by non-auditory stimuli that convey the same meaning, such as visual images of monkeys producing vocalizations.

Primates developed close-up eyesight to avoid a dangerous predator

Sat, 22 Jul 2006 19:14:37 PST

( from http://www.rxpgnews.com ) The ability to spot venomous snakes may have played a major role in the evolution of monkeys, apes and humans, according to a new hypothesis by Lynne Isbell, professor of anthropology at UC Davis.

Primates have good vision, enlarged brains, and grasping hands and feet, and use their vision to guide reaching and grasping. Scientists have thought that these characteristics evolved together as early primates used their hands and eyes to grab insects and other small prey, or to handle and examine fruit and other foods.

Isbell suggests instead that primates developed good close-up eyesight to avoid a dangerous predator -- the snake.

"A snake is the only predator you really need to see close up. If it's a long way away it's not dangerous," Isbell said.

Neurological studies by others show that the structure of the brain's visual system does not actually fit with the idea that vision evolved along with reaching and grasping, Isbell said. But the visual system does seem to be well connected to the "fear module," brain structures involved in vigilance, fear and learning.

Fossils and DNA evidence show that snakes were likely the first serious predators of modern mammals, which evolved about 100 million years ago. Fossils of snakes with mouths big enough to eat those mammals appear at about the same time. Other animals that could have eaten our ancestors, such as big cats, and hawks and eagles, evolved much later.

Venomous snakes evolved about 60 million years ago, raising the stakes and forcing primates to get better at detecting them.

"There's an evolutionary arms race between the predators and prey. Primates get better at spotting and avoiding snakes, so the snakes get better at concealment, or more venomous, and the primates respond," Isbell said.

Some primate groups less threatened by snakes show fewer signs of evolutionary pressure to evolve better vision. For example, the lemurs of Madagascar do not have any venomous snakes in their environment, and in evolutionary terms "have stayed where they are," Isbell said. In South America, monkeys arrived millions of years before venomous snakes, and show less specialization in their visual system compared with Old World monkeys and apes, which all have good vision, including color.

Having evolved for one purpose, a good eye for color, detail and movement later became useful for other purposes, such as social interactions in groups.

Parsing the Functional Fields of the Auditory Cortex

Fri, 23 Jun 2006 00:42:37 PST

( from http://www.rxpgnews.com ) No self-respecting concertgoer of a certain era would consider wearing earplugs at a show, but that was long before Pete Townsend and other rock icons spoke out about the risk of deafness. Today, most people recognize that high-intensity noise causes hearing lossexcept maybe for those iPod users who routinely blast earsplitting music straight into their brains.

Blaring volume causes deafness by destroying sound-responsive hair cells, but it's unclear how these auditory assaults affect the brain's auditory system. Much of the auditory cortex is organized by sound frequency, but neuroscientists are still figuring out the extent of the spatial organization of frequency-selective neurons and how each auditory field contributes to sound perception. While neurophysiological studies have characterized the functional properties of certain auditory cortical fields (by recording the electrical activity from individual neurons), anatomical studies have identified other fields that had not been functionally characterized.

A new study by Christopher Petkov, Nikos Logothetis, and colleagues fills in some of these gaps by using high-resolution functional magnetic resonance imaging (fMRI) on macaque monkeys presented with acoustic stimuli. The researchers used the anatomical and neurophysiological data to see how the fMRI data compared with the already described auditory cortical fields. With a better sense of how to interpret the functional imaging data, they could use fMRI to probe the functional properties of uncharacterized auditory fields. This approach allowed them to show the functional organization of 11 discrete auditory fields in the primate auditory cortexan important step toward understanding how these fields operate together to shape what the primate listener perceives of its acoustical environment.

Petkov et al. first used a broad spectrum of sound frequencies to globally activate the monkeys' auditory cortex. (Six anesthetized monkeys and one monkey trained to stay still were placed in fMRI scanners while presented with acoustical stimuli.) Next, they used low- and high-frequency sounds to identify regions with selectively tuned neurons. Based on predictions that auditory fields follow an alternating pattern of high to low frequency along a posterior to anterior direction, they expected fMRI activity to follow the same patternwhich it did. This now grounded frequency gradient allowed them to match the rest of the activity patterns that they observed with other auditory fields. Significantly, they matched an alternating pattern of high- and low-frequency selective regions with three fields in the primary auditory cortex, or auditory core fields: A1, R, and RT. These core fields are thought to be surrounded by seven or eight so-called belt (non-primary) fields. However, neurophysiological data on RT and many of the belt fields are scant, making it unclear how many functional fields actually exist.

It's thought that auditory fields in the core are tuned to simple sounds, like single-frequency tones, while fields in the belt respond to complex sounds. To better locate activity in the belt regions, Petkov et al. also studied brain responses to more-complex sounds. The results included frequency selectivity patterns consistent with known patterns for four belt fields that had previously been studied neurophysiologically and provided a base outline for the other fieldsbasically functionally tessellating the monkey auditory cortex. Petkov et al. then took advantage of evidence that tones produce a stronger response in the core than they do in the belt fields to outline a border between the core and belt, which helped them to further resolve the position of the core relative to the belt fields.

The extensive patterns of frequency gradients indicated that the three core regions were surrounded by eight belt fields, four on each side, supporting anatomical evidence for about a dozen auditory fields. The researchers then went on to show that neurons in the belt fields responded preferentially to sounds with a broad frequency spectrumin other words, more complex sounds that would have some of the properties of natural sounds. These results fall in line with a model of hierarchical auditory processing in which the core operates during the initial stages of auditory cortex processing, contributing to a frequency analysis of the sounds in the environment. The belt fields function at a higher level to deal with more-complex sounds by integrating sound frequencies. The challenge now is to understand how each of the many fields contributes toward and interacts with others to shape the perception of primates in their typically opulent acousticaland multisensoryenvironments.

This study underscores the value of pooling data from different experimental approaches to study something as intricate as the brain. With this high-resolution functional MRI map of the monkey auditory cortex, researchers can now use both fMRI and neurophysiological techniques to refine each field's particular role within the primate auditory cortex. The map will also guide efforts to better understand the functional organization of the human auditory systeminformation that could certainly identify the impact of peripheral hearing loss on this part of the auditory system. And with functional maps of both monkey and human auditory cortex, researchers can better understand how the specialized auditory fields evolved, ultimately offering insights into the evolution of human language.

Declining Human Fertility is Evolutionary Adaptation

Wed, 21 Jun 2006 14:51:37 PST

( from http://www.rxpgnews.com ) Before society criticises teenage girls for having sex behind the bike sheds and becoming pregnant, or women in their 60s for seeking IVF treatment, it is important to consider fertility not just in terms of the 21st century but in the context of the past 150,000 years.

Dr Laurence Shaw, told the 22nd annual conference of the European Society of Human Reproduction and Embryology, that it is only in the past 150 years or so that better hygiene, living conditions and medical advances have made it relatively common for people to live into their 60s, 70s, 80s and sometimes beyond. Before that time men and women would have been more likely to die around the age of 50. For women this often meant they died at or before their menopause.

Dr Shaw, deputy medical director, at the Bridge Centre, London, UK, will say: "Homo sapiens has existed for 150,000 years and for all of that time until about 100 to 150 years ago, women had their babies when they were in their late teens and early twenties when their fertility was at its peak. In the subsequent 20 to 30 years, they raised their children, and their declining fertility meant that they were less likely to have further children of their own and could help their daughters to tend their own babies. Most women died before they reached menopause or shortly after.

"Therefore, the accelerated decline in fertility, rather than the menopause itself, is the evolutionary adaptation that has occurred in the human line over the past 2.8 million years, and, until the last 150 years, the postmenopausal state and the prior decline in fertility was positively useful. Living through the menopause and beyond is not a part of our natural life.

"Our improved longevity and other aspects of industrialised society have some incompatibilities with this evolutionary strategy. In particular, there are three serious issues:

1. Our natural time to have children, and the peak of our fertility, is late teens and early twenties, yet Western society regards teenage pregnancy as a 'problem' and cannot cope well with them.
2. We delay our childbearing until we have wealth and stability in later life when women's fertility is declining and then require medical assistance that is often poorly funded by governments.
3. Women now expect to spend more than a third of their life in the post-reproductive part of their life an unnaturally prolonged hormone deficient state when they encounter problems such as osteoporosis with increasing frequency, which they never had to face until recent decades. Worry about the risks of hormone replacement therapy is still seen by some as more relevant than the risk of prolonged hormone deficiency.

"Therefore, before we condemn our teenagers for having sex behind the bike sheds and becoming pregnant, we should remember that this is a natural response by these girls to their rising fertility levels. Society may 'tut, tut' about them, but their actions are part of an evolutionary process that goes back nearly two million years; whilst their behaviour may not fit with Western society's expectations, it is perhaps useful to consider it in the wider context.

"Similarly, we should not be quite so prejudiced about older women who want fertility treatment. Before we criticise 62-year-old women who want to have babies, we should remember that it was not so long ago that women would only have had about 20 or 30 years to care for their offspring and help with the next generation. Nowadays 60-year old women in many industrialised countries, have a life expectancy of 80 or 90, so there is no difference in terms of the length of their survival after the birth of a baby than there would have been for most of human existence."

Although Dr Shaw says that he feels that IVF treatment for women in their 60s would reasonably be considered an excessive burden for state-funded national health services, he thinks the problems associated with women wanting to start families after their fertility has started to decline and their longer life after menopause should be addressed by society, including the medical profession.

"The menopause is not natural because, until recently, we generally didn't live that long. Rapidly declining fertility after the late 20s is a long-term evolutionary adaptation, but a more recent adaptation is our longevity, helped by better hygiene, medicine and so on. So I believe that we should use this same technology to help further with finding better and safer hormone replacement therapies, and with fertility treatments for those seeking pregnancy in their 30s and 40s. We need to look at things not just in terms of the 21st century, but in the overall context of evolutionary progress."

Study shows that threat displays may prevent serious physical harm

Tue, 20 Jun 2006 23:16:37 PST

( from http://www.rxpgnews.com ) In a paper from the July issue of The American Naturalist, Kristopher Lappin (Northern Arizona University), Yoni Brandt (University of Toronto), Jerry Husak (Oklahoma State University), Joe Macedonia (Arizona State University), and Darrell Kemp (James Cook University), demonstrate that a threat display can provide accurate information about the performance of a weapon.

Working at the Wichita Mountains National Wildlife Refuge in Oklahoma, the researchers showed that when an adult male lizard gapes his jaws at a rival male during an intense territorial interaction, information is made available to his opponent about how hard he can bite indeed, the lizard's jaw muscles become clearly visible. Further, some lizards have evolved bright patches that reflect ultraviolet light, which lizards can see, to delineate the jaw muscles.

Lappin and colleagues point out that the information about bite force provided by the display does not correspond to body or head size because males of similar size can vary substantially in how hard they can bite. The display thus provides unique and honest information about weapon quality, as well as a mechanism for making the decision to fight or to back down. Adult male collared lizards (the species examined in this study) are larger than the females, have hypertrophied jaw muscles, and are highly territorial toward other males. All of this relates to males having evolved the ability to bite with great force, which means that they can seriously wound rivals in fights.

The colorful and robust head of an adult male eastern collard lizard (Crotaphytus collaris) from the Wichita Mountains National Wildlife Refuge. The partially unfolded, bright white mouth-corner patch accentuates the jaw muscles during gaping displays. Credit: Courtesy A.K. Lappin

"When you've seen what these lizards can do to each other with their jaws, inflicting deep lacerations and even breaking bones, it makes sense that avoiding fights would be advantageous, even if you are likely to win," Lappin says.

When two competing males engage in a gaping display, each shows off its weapon while simultaneously affording an opportunity to evaluate its rival's weapon. In animals from insects to humans, such displays likely play an important role in assessing the risks associated with fighting, as well as in reinforcing the experiences of past fights with specific individuals.

"You see the same with humans," Lappin explains. "Think back to the rivalries of adolescence. Fights took place in order to establish dominance relationships in the neighborhood, but the fights themselves were rare. Most of it was posturing and showing off, displays per se, that served to advertise physical prowess as well as to reinforce the consequences of previous confrontations."

How animals learn from each other

Tue, 20 Jun 2006 00:32:37 PST

( from http://www.rxpgnews.com ) In an exciting study that provides new understanding of how animals learn--and learn from each other--researchers have demonstrated that bats that use frog acoustic cues to find quality prey can rapidly learn these cues by observing other bats. While numerous examples are known of instances where predators can use so-called "social learning" to learn new visual and olfactory cues associated with prey, this kind of learning of an acoustic cue had not been previously described.

The fringe-lipped bat, Trachops cirrhosus, uses frog calls from different species as acoustic cues to assess the palatability of its prey. Previous experiments have shown that T. cirrhosus is extremely flexible in its foraging behavior. In the new study, Page and Ryan investigated the role of social learning in bat foraging flexibility. Comparing three different learning groups, the researchers measured the rate at which bats learned new foraging information: in this case, the novel (experimental) association of the calls of a poisonous toad species with the presence of palatable prey.

The researchers tested the effectiveness of learning this experimental association through three different means: (a) a social learning group, in which a bat inexperienced with the new call-food association was allowed to observe an experienced bat; (b) a social facilitation group, in which two inexperienced bats were presented with the experimental task together; and (c) a trial-and-error group, in which a single inexperienced bat was presented with the experimental task alone. In the social learning group, bats rapidly acquired the novel association in an average of 5.3 trials. In the social facilitation and trial-and-error groups, most bats did not approach the call of the poisonous species even after 100 trials. These results suggest that once acquired, novel prey-cue/prey-quality associations could spread rapidly through bat populations by cultural transmission.

Thermal Adaptation in Bacterial Viruses

Sat, 10 Jun 2006 13:15:37 PST

( from http://www.rxpgnews.com ) Assuming the absence of a massive asteroid strike, gamma ray burst, or other globally devastating event, the survival of a species depends on its ability to adapt to environmental changes. To understand how such adaptations occur in nature, scientists study much simpler systems in the lab. A classic lab evolution experiment uses evolutionary responses to temperature as a model for studying how an environmental variable affects the physical expression (phenotype) of an organism's genes. Biologists have typically focused either on the range of physiological responses to temperature or on the genetic changes underlying variations in temperature.

In a new study, Jennifer Knies, Christina Burch, Joel Kingsolver, and colleagues demonstrate the value of using a genetically tractable organismthe bacteria-infecting virus bacteriophage (or phage)to study adaptive responses to temperature. By combining phenotypic and genetic analyses with a new statistical approach, the researchers show that the genetic changes they observed in phages undergoing thermal adaptations in the lab also play a role in thermal performance in natural populations.

A graphical representation of the effect that temperature (the environmental variable) has on a population's growth rate (the performance indicator) is called a thermal reaction norm. (A continuous reaction norm shows these interactions as an ongoing, underlying relationship.) Thermal reaction norms usually have a common shape, showing performance increasing along with temperature, reaching a maximum at an intermediate temperature, and declining with additional temperature increases. Three basic variations on this curve reflect biological responses (see illustration): vertical shifts relate to average performance, horizontal shifts relate to optimal temperature (for growth rate, for example), and width shifts relate to changes in niche range.

Using continuous reaction norms to characterize adaptive responses to temperature, the researchers reexamined a recent study that linked rapid adaptation to specific genetic changes. The study, by Holder and Bull, showed that phage populations quickly evolved higher growth rates at higher temperatures. But, Knies et al. explain, these growth rates were correlated with just one temperature pointthe optimal temperature for the ancestral populations (used at the beginning of the experiment). Knies et al. reexamined phage thermal adaptation by measuring growth rate over a wider range of temperatures, then used a recently developed statistical method to identify the biological determinants of the shifts in the reaction norm shapes, quantify their relative contributions, and identify the genetic basis of the adaptations.

In the evolution experiment, a population of phage clones was propagated through a series of 50 transfersduring each transfer, 1,000,000 phages were added to a culture of 1,000,000,000 reproducing Escherichia coli hostsat 106.7 degrees Fahrenheit (41.5 °C), followed by 50 more transfers at 111.2 °F (44 °C). Knies et al. isolated phages from the evolving populations at the 20th, 50th, and 100th (last) transfer, and characterized their growth rates (and that of the ancestral population) across their entire thermal nichesix temperature points between 80.6 °F (27 °C) and 111.2 °F.

The phages had evolved between each transfer, and their reaction norms had the characteristic shape for performance: growth rate increased with temperature until reaching a maximum at 95 °F (35 °C), and declined as temperatures further increased. Using the statistical model, the researchers estimated the biological components underlying the reaction norm shapes for each evolving population. Although the contributions of the components varied with temperature, Knies et al. found that optimal temperature explained the largest proportion of the variation in reaction norm shape, with smaller contributions from growth rate and niche width.

The researchers knew from the previous study by Holder and Bull that ten adaptive mutations had spread through the population during adaptation to high temperature. By sequencing the genomes of several evolved phages at different transfer stages, they were able to confirm that many of these mutations contributed to adaptation in the laboratory. To determine the effects of these mutations in natural populations, they focused on one mutation that unambiguously contributed to adaptation in the lab and was also present in natural populations. In both laboratory and natural phage populations, the mutation was associated with increased growth rates at high, but not low, temperatures.

The finding that shifts in optimal temperature underlie much of the adaptive response in phage populations supports human antiviral strategies that use cold-adapted vaccines, the researchers argue. These strategies adapt viral strains to grow at temperatures well below body temperature so they don't become virulent when injected as vaccinesa sound approach, based on these results. This study demonstrates a powerful method for integrating biological modes of adaptation to the underlying genetic changesa method the researchers hope will inspire more collaborations between evolutionary geneticists, physiologists, and statisticians.

Genetic quality of sperm worsens as men get older

Thu, 08 Jun 2006 16:45:37 PST

( from http://www.rxpgnews.com ) New research indicates that the genetic quality of sperm worsens as men get older, increasing a man's risk of being infertile, fathering unsuccessful pregnancies and passing along dwarfism and possibly other genetic diseases to his children.

A study led by scientists at Lawrence Livermore National Laboratory (LLNL) and the University of California, Berkeley, found a steady increase in sperm DNA fragmentation with increasing age of the study participants, along with increases in a gene mutation that causes achondroplasia, or dwarfism. The first changes were observed in men in their early reproductive years.

Earlier research by the same team indicated that male reproductive ability gradually worsens with age, as sperm counts decline and the sperm lose motility and their ability to swim in a straight line. In the current study, the researchers analyzed DNA damage, chromosomal abnormalities and gene mutations in semen samples from the same subjects 97 healthy, non-smoking LLNL employees and retirees between 22 and 80 years old and found that sperm motility showed a high correlation with DNA fragmentation, which is associated with increased risk of infertility and a reduced probability of fathering a successful pregnancy.

The study, "Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies (chromosome abnormalities) in sperm," appears this week in the online edition of the Proceedings of the National Academy of Sciences.

"This study shows that men who wait until they're older to have children are not only risking difficulties conceiving, they could also be increasing the risk of having children with genetic problems," said co-lead author Andrew Wyrobek of LLNL.

"We know that women have a biological time clock," said co-lead author Brenda Eskenazi of UC Berkeley's School of Public Health, "with an increase in risk of miscarriage and producing children with trisomy (an extra chromosome, such as in Downs syndrome) as women age, and with a seemingly abrupt end of fertility around perimenopause. Our research suggests that men, too, have a biological time clock only it is different. Men seem to have a gradual rather than an abrupt change in fertility and in the potential ability to produce viable healthy offspring."

Mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene (above) have been linked to achondroplasia, or dwarfism. Sperm analysis shows that mutations associated with dwarfism gradually increased by about two per cent for every year of age. (LANL)

Unlike in women, the researchers found no correlation between male aging and chromosome changes that cause Down's syndrome and other forms of trisomies such as Klinefelter syndrome, Turner syndrome, triple X syndrome, and XYY in offspring that are associated with varying types and severity of infertility as well as physical and neurological abnormalities. They did conclude, however, that some older men could be at risk for fathering children with dwarfism, and that "a small fraction of men are at increased risks for transmitting multiple genetic and chromosomal defects."

In the case of Apert syndrome, a serious disfiguring birth defect, the researchers found that the effects of advancing male age may differ among different groups of men. Apert syndrome gene mutations increased in the sperm of a second group of men recruited in the Baltimore inner city by researchers at Johns Hopkins Medical Center, while no age effects were observed in the group of men recruited in California.

Wyrobek noted that these differences in finding suggest that factors other than age may be involved, raising the possibility that socioeconomic or dietary factors or ethnic background may also be involved in how age affects the quality of human sperm.

"Since some forms of genomic damage change with age and others don't," he said, "overall genomic sperm quality cannot be measured by any single sperm test." Dwarfism, a genetic disorder that affects bone growth, is the most common growth-related birth defect, occurring in about one in every 25,000 births. It occurs in all races and in both males and females and causes affected individuals to have very short arms and legs, limiting their full adult height to about four feet.

Wyrobek, Eskenazi and their colleagues analyzed semen from the volunteers using a variety of state-of-the art methods for detecting genetic and chromosomal defects in human sperm. A flow cytometer method was used to detect DNA fragmentation and chromatin defects in collaboration with co-author Don Evenson at South Dakota State University. Gene mutations in the achrondroplasia gene and in the Apert sydrome gene were measured using highly sensitive PCRbased methods developed by co-authors Ethylin Jabs at Johns Hopkins and Norman Arnheim at USC in Los Angeles. The team also used a Livermore-developed chromosome analysis system called sperm FISH (fluorescence in-situ hybridization). They found a strong correlation between age and sperm DNA fragmentation, with genetic mutations associated with dwarfism gradually increasing by about two per cent for every year of age.

The study included at least 15 men from each age decade from 20 to 60 years, and 25 men 60 to 80 years old. The researchers gathered extensive medical, lifestyle and occupational exposure history from the men and excluded current cigarette smokers and men with current fertility or reproductive problems, a previous semen analysis with zero sperm count, vasectomy, history of prostate cancer or undescended testicle, or exposure to chemotherapy or radiation treatment for cancer.

Understanding the effects of paternal age has become more important as increasing numbers of men are having children at older ages. Since 1980 there has been about a 40 percent increase in 35- to 49-year-old men fathering children, and a 20 percent decrease in fathers under 30. Studies have also shown that it takes longer for older men to conceive, even when the age of the mother is considered.

Songbirds boost size of eggs when hearing sexy song

Thu, 08 Jun 2006 06:03:37 PST

( from http://www.rxpgnews.com ) In a new study published in the latest issue of Ethology researchers show that female songbirds can alter the size of eggs and possibly the sex of their chicks according to how they perceive their mate's quality.

The researchers played back attractive ("sexy") songs and less attractive control songs of male canaries to female domesticated canaries. When the females started egg-laying they varied the size of their eggs in the nest according to the attractiveness of the male's song. That is, the more attractive the song, the larger the eggs. However it is remarkable that while larger eggs were more likely to contain male offspring in natural environments, in the experiment there was no difference in brood sex ratio between the different songs played to the females, which suggests different levels of female control. Male birdsong has long been known to attract females and influence mate choice decisions and even induce an alteration in the offspring's sex ratio. This study by Leitner et al. now shows experimentally that hearing attractive song also has a selective impact on female physiology.

45 female domesticated canaries participated in this study that was a collaboration of Royal Holloway, University of London and the Max Planck Institute for Ornithology in Seewiesen and Radolfzell in Germany. The birds were kept in large aviaries where their daily behaviour was monitored in a colony before they were tested in the song experiments. The females showed a remarkable consistency in their behavioural and reproductive performance and the song stimuli alone were sufficient to elicit a profound physiological change. This study further highlights the importance of behavioural stimuli for reproductive physiology.

Why women live longer than men

Wed, 10 May 2006 12:48:37 PST

( from http://www.rxpgnews.com ) Despite research efforts to find modern factors that would explain the different life expectancies of men and women, the gap is actually ancient and universal, according to University of Michigan researchers.

"Women live longer in almost every country, and the sex difference in lifespan has been recognized since at least the mid-18th century," said Daniel J. Kruger, a research scientist in the U-M School of Public Health and the Institute for Social Research. "It isn't a recent trend; it originates from our deep evolutionary history."

This skewed mortality isn't even unique to our species; the men come up short in common chimps and many other species, Kruger added.

Kruger and co-author Randolph Nesse, a professor of psychology and psychiatry and director of the Evolution and Human Adaptation Program, argue that the difference in life expectancy stems from the biological imperative of attracting mates.

"This whole pattern is a result of sexual selection and the roles that males and females play in reproduction," Kruger said, "Females generally invest more in offspring than males and are more limited in offspring quantity, thus males typically compete with each other to attract and retain female partners."

For example, in common chimps, the greatest difference in mortality rates for males and females occurs at about 13 years of age, when the males are just entering the breeding scene and competing aggressively for social status and females.

From the tail of the peacock to the blinged-out SUV, males compete aggressively for female attention, and that costs them something. In nature, it means riskier physiology and behavior for the males, such as putting more resources into flashy plumage or engaging in physical sparring.

And even in modern life, where most dueling is a form of entertainment, male behavior and physiology is shortening their lifespans relative to women, Kruger said. In fact, modern lifestyles are actually exacerbating the gap between male and female life expectancies.

Male physiology, shaped by eons of sexual competition, is putting the guys at a disadvantage in longevity. Male immune systems are somewhat weaker, and their bodies are less able to process the fat they eat, Kruger said. And behavioral causes---smoking, overeating, reckless driving, violence---set men apart from most women. "Because mortality rates in general are going down, behavioral causes of death are ever more prevalent," Kruger said.

Looking at human mortality rates sliced by socioeconomic status shows that the gender gap is affected by social standing. Human males in lower socio-economic levels tend to have higher mortality rates than their higher-status peers. The impact of social standing is greater on male mortality than on female mortality, Kruger noted, partially because males who have a relatively lower status or lack a mate engage in a riskier pattern of behaviors in an attempt to get ahead, he said.

Fruitfly study shows how evolution wings it

Thu, 20 Apr 2006 15:55:37 PST

( from http://www.rxpgnews.com ) In the frantic world of fruitfly courtship, the difference between attracting a mate and going home alone may depend on having the right wing spots. Now, Howard Hughes Medical Institute researchers have learned which elements of fly DNA make these spots come and go in different species. Their studies have also uncovered surprising new evidence supporting the idea that evolution is an incessant tinkerer when it comes to complex traits.

The experiments are among the first to root out "the deep mechanics of evolution" that underpin complex traits, according to the study's senior author Sean Carroll, a Howard Hughes Medical Institute researcher at the University of Wisconsin-Madison. Carroll and his Wisconsin colleagues collaborated with researchers from the University of Cambridge and Stony Brook University on the studies, which were published in the April 20. 2006, issue of the journal Nature.

The researchers said their findings emphasize the evolutionary significance of "pleiotropic" genes those with multiple on-switches that enable the expression of a single gene in different tissues or at different stages of development.

"The wing spot on the fruitfly is a particularly good model because we know it constitutes a new feature that is gained or lost by evolution in different species," said Carroll. "And, since it is a spatial pattern, it gives us a chance to analyze the evolution of a physical trait. Such traits have size, shape, and length, and they are more complicated than physiological traits. For example, eye color is not a tricky thing to figure out, since it can be reduced to single genetic changes. But evolutionary biologists want to understand how even complicated bits of anatomy and machinery like the wing or the complex eye are put together in the course of evolution."

Wing spots have evolved in different fruitfly species as part of the courtship displays that males present to females during mating. Thus, they can be under intense evolutionary pressure to appear and be maintained, depending on whether the females find them "attractive," Carroll noted.

In their study, the researchers first organized 77 species of the fruitfly Drosophila into a fly family tree to reveal which species had gained or lost wing spots in comparison to their ancestors. The researchers then analyzed the genetic mechanisms that caused two of the species to gain wing spots independently in comparison to ancestral flies which did not have the wing spots. The researchers also performed similar analyses on two species of flies that had lost wing spots.

Their genetic studies focused on the role of DNA segments called cis-regulatory elements that were thought to be involved in the evolution of wing spots. Cis-regulatory elements (CREs) are DNA segments that nestle around DNA sequences that code for specific proteins and dictate where and when a gene is turned on or off in the body. By having different CREs, the gene's function can vary in different tissues between species.

In earlier studies, Carroll's team had shown that CREs regulating a gene called yellow played a central role in wing spot development. Their studies showed that when a CRE switches on the yellow gene, it produces a spot's black pigment. CREs are important targets for evolutionary experimentation because they can be mutated without compromising the basic function of the gene, said Carroll.

The researchers' comparison of the different species revealed that all the gains or losses of spots involved mutations that altered CREs for the yellow gene. The scientists found that losses of spots in two different groups of Drosophila species involved different, independent mutations in the same CRE. However, said Carroll, the bigger surprise came when they studied the gains of spots in different species.

"The big stunner in this paper was that the two independent gains of spots we studied each resulted from mutations in distinct ancestral CREs," said Carroll. "In the ancestor, one of these CREs controls the expression of the yellow gene in the wing blade and one in the vein.

"This finding is informative because it shows that the wing pattern wasn't generated from scratch," said Carroll. "The fly didn't use naïve DNA that had no job and invent this pattern out of thin air. It used a gene that was already active in the wing, already drawing some kind of pattern in the wing, and modified that pattern. We think that is strong clue to how nature invents, which is by using material that is already available. This demonstrates how evolution is a tinkerer," he said.

The findings also underscore an important role for pleiotropic genes in evolution. "For example, a fly's body has pigmented bristles, mouth parts, thorax and abdomen. These different features are controlled separately, so the same yellow gene can be used in different parts of the body. So this pleiotropy gives evolution an artistic freedom to play with the regulatory elements in specific regions without making mutations that would affect the gene throughout the body."

Carroll said that his future studies will explore how evolution can tinker with the machinery of the fly's nervous system to affect behaviors such as male mating dances and courtship songs, as well as how those are perceived by the female.

More generally, these kinds of molecular studies are enabling new advances in understanding the machinery of evolution. "These techniques are enabling dramatic progress in understanding the deep mechanics of evolution in more and more detail," he said. "Researchers are now finding the actual 'smoking guns' of evolution by documenting specific evolutionary changes at the DNA level.

"And studies of phenomena such as fruitfly wing spots show how evolution is not some one-off process. It repeats itself over and over.

They show that there is more than one way to tinker with the same gene, and by extension, to independently evolve the same trait," Carroll said.

Tantalizing clue to the evolutionary origins of light-sensing cells

Sat, 15 Apr 2006 18:03:37 PST

( from http://www.rxpgnews.com ) Lizards have given Johns Hopkins researchers a tantalizing clue to the evolutionary origins of light-sensing cells in people and other species.

Published in the March 17 issue of Science, their lizard study describes how the side-blotched lizards so-called third, or parietal, eye, distinguishes two different colors, blue and green, possibly to tell the time of day. Specialized nerve cells in that eye, which looks more like a spot on the lizards forehead, use two types of molecular signals to sense light: those found only in simpler animals, like scallops, and those found only in more complex animals like humans.

Although the blue-green color comparison method used by the parietal eye is not one shared by humans, it does reveal one potential step in the evolution of color vision, the Hopkins researchers say.

Human light-reception cells responsible for color vision are called cone cells or photoreceptors, and they contain only one kind of pigment per cell red, green, or blue. A color image results when light-triggered signals in the three different types of cone cells are compared by other nerve cells in the retina as well as the brain.

The lizards parietal eye photoreceptors contain two pigments per cell, blue and green. Having two different pigments allows the cell to respond to two different colors of light and process that information within the same cell.

According to the researchers, when the lizards third eye sees blue light, the blue pigment triggers a molecule called gustducin, which is very similar to a molecule found in human photoreceptors as well as the lateral eyes of the lizard those on the sides of its head. But when the lizards third eye sees green light, the green pigment triggers a different molecule called Go, known as G-other, which also signals light responses in the light-sensing cells of the scallop and other creatures without a backbone. That Go is found in spineless creatures suggests it is the evolutionarily more ancient light-triggering signal.

Although gustducin and Go are different molecules, they are similar and considered related proteins. However, gustducin and Go each activate different molecular pathways that work against each other physiologically. Blue light and gustducin generate an off response in the nerve cell while green light and Go generate an on response.

It may seem strange to have two opposing signals in the same cell, says the studys senior author, King-Wai Yau, Ph.D, a professor in the Solomon H. Snyder Department of Neuroscience at Hopkins, but the unique mechanism renders these parietal photoreceptors most active at dawn and dusk.

So incorporating two different pigments and two separate signaling molecules in one cell may have been an economical way, in a primitive eye with relatively few cell types, to tell the transitions of the day based on changes in the spectrum of sunlight, says Chih-Ying Su, Ph.D., the first author of the study and a former neuroscience graduate student at Hopkins.

Its just like in a small company, says Yau. You have to delegate each person to do more things.

By sharing features found in human photoreceptors as well as those found in simpler organisms like the scallop, the researchers propose that the lizards parietal eye photoreceptor cells represent a missing link between the light-sensing apparatus in lower animals and ours.

It turns out that some frogs and fish also have a spot on their foreheads that might play the role of a light-sensing third eye. Yau hopes to pursue these structures to obtain more clues about how our photoreceptor cells, the rods and cones, came about. As he says, hes most curious about how the same function can be achieved in different ways in different animals.

Relationship of brain and skull more than just packaging

Fri, 14 Apr 2006 23:16:37 PST

( from http://www.rxpgnews.com ) People usually think of the skull as packaging for the brain and researchers usually investigate them separately, but a team of researchers now thinks that developmentally and evolutionarily that the two are incontrovertibly linked.

The researchers, including biological anthropologists, physicians and a computer scientist, looked at the CT scans and MRIs of infants with particular types of craniosynostosis a condition where one or more of the sutures -- fibrous bands that connect the bones -- of the baby's skull close too early and deform the skull and brain.

"We are interested in understanding craniosynostosis," says Dr. Joan T Richtsmeier, professor of biological anthropology at Penn State. "We would like to know why it happens, especially when it is not part of a syndrome, but when it occurs alone."

The researchers report in a recent early online publication of the Journal of Experimental Zoology: Molecular and Developmental Evolution: "Our study represents the first empirical evidence of phenotypic integration of brain and skull in 3D, although indirect evidence has been accumulating for years."

The researchers are also interested in understanding how the skull and brain change jointly through evolution. Vertebrate evolution shows a trend toward fewer skull and jaw bones and loss of some intercranial joints. While craniosynostosis is considered a pathology in modern humans, it shares with evolutionary history a reduction in cranial elements and coincident changes in the shape of the skull and brain. The researchers believe that studying craniosynostosis could shed light on the joint evolution of the brain and skull.

The two types of craniosynostosis the researchers studied were early closure of the sagittal suture the suture that runs down the center of the skull from front to back and unilateral coronal craniosynostosis, early closure of one side of the suture that runs across the top of the head from ear to ear.

Children with craniosynostosis almost universally have surgery to reopen the sutures and allow normal growth of the boney plates of the skull. Premature closure of sutures causes the skull and the brain beneath to deform. However, the researchers had few CT and MRI images to work with because even if both CT and MRI are acquired for a patient, they are rarely obtained the same day.

"We are extremely conservative in requiring that the two types of images be taken within a 24-hour period," says Richtsmeier. "Early brain and skull growth are so rapid that if the images were taken weeks apart, they would not be an exact fit." T scans record a three-dimensional image of the skull while MRIs provide a three-dimensional brain image.

The researchers caution that the number of infants studied in this way is small at this point, but they found that the brain and skull are strongly integrated.

"We also expected to see higher correlation among those brain and skull measures that were close to each other anatomically, but we did not," says Richtsmeier. "We found that the stronger statistical relationships existed between neural structures located near the top of the brain and boney features at the base of the skull."

To look at the correlations between the skull and the brain, the researchers first had to find locations that could be accurately found again and again. Locating reliable markers was easier on the rigid skull than on the brain. Co-author of the paper, Kristina Aldridge, former postdoctoral researcher at Penn State and now at Washington University, looked at the reproducibility of standard anatomical features on the skull and brain.

"We found that the brain landmarks people often use were highly variable and had the biggest errors in reproducibility," says Richtsmeier. "We eventually chose brain locations that were easier to identify reliably such as the most posterior point or the centroid of small neural structures."

The researchers did not compare one brain to another or one skull to another, nor did they use the data in a coordinate system. Instead, they measured the correlations between measure taken on brain and those taken on skull. Overall, they found that the correlations between brain and skull were very high.

Because normal infants almost never have MRIs and CT scans done at the same time, there are no controls available with which to compare the correlation of skull with brain measurements. Because even infants with craniosynostosis usually do not have both CT scans and MRIs done on the same day, the available study population is small, however, the researchers plan to increase the number of infants studied.

Richtsmeier notes that, from a medical point of view, the researchers want to find genetic mechanism underlying craniosynostosis so that the problem can be prevented or cured. From an evolutionary point of view, researchers focus on the developmental basis for the physical change observed in the fossil record and propose hypotheses about the evolution of the genetic traits responsible for these changes. The researchers propose that the genetic basis of the complex regulatory sequences that cause the changes documented in craniosynostosis infants may also account for the changes observed in the evolution of the vertebrate skull.

What Does Evolution Do with a Spare Set of Genes?

Wed, 05 Apr 2006 18:43:37 PST

( from http://www.rxpgnews.com ) A hundred million years ago, a molecular twist of fate endowed an ancestor of today's baker's yeast (Saccharomyces cerevisiae) with an extra copy of every gene it ownedthe equivalent of a factory one day finding double the number of workers reporting for duty. What did the yeast and the forces of evolution do with this treasure trove of potential? Did the extra gene-workers simply double the output? Did the original crew and the duplicates divvy up the ancestral functions? Or did they take on new tasks? That's what Gavin Conant and Kenneth Wolfe sought to find out in their study of the networks of interactions among genes and other cellular components that emerged in the wake of that landmark event.

Some of the genes from the original doubling disappeared completely from the S. cerevisiae genome in the intervening millennia. But previous research had identified 551 duplicate gene (paralog) pairs that remain. To explore their fate, the authors used information about known co-expression from other S. cerevisiae studies along with an algorithm they developed on these genes pairs, and they identified 19 networks made up of paralogs divided such that there are many interactions within each network but few between the two paired networks. They then set out to explore the extent to which the networks composed of the two sets of paralogs differed from each othera measure of the degree to which they had diverged evolutionarily, and so taken on separate functions, over time.

The first test looked at symmetry between the networks formed by the two sets of paralogs. The researchers found that for many of the network pairs, one set of paralogs had significantly more interactions than the other. The networks also had more redundancymultiple interactions between two pairs of paralogsthan would be found in randomly grouped networks. These findings suggest substantial but incomplete divergence since the original gene-duplicating event.

Second, the authors explored the extent to which the 19 networks they had identified showed evidence of functional significance. To do so, they split the 551 paralog pairs into random networks, then recalculated network partitions for each. Eight of the networks showed significantly better clustering of gene interactions with respect to co-expression data than did the randomized networks, supporting the contention that they do in fact represent modular functional units, not just mathematical constructs. To further provide evidence of potential functionality, the researchers also analyzed whether partitions contained proteins with similar cellular localization and/or upstream regulatory sequence motifs. In the two largest of the networks with significant partitioning, protein localization and regulatory sequences were better conserved within each of the network partitions than would be expected by chance, confirming the functional correspondence seen with gene co-expression data.

To illustrate the adaptive value of network partitioning, the authors described a pair of paralogs whose protein products catalyze the last reaction in glycolysis. One encodes an enzyme induced by a compound present when glucose levels are high, while the other encodes an enzyme that works without this metabolic intermediate. As a result, the yeast can efficiently carry out the reaction in both high- and low-glucose environments.

Finally, the authors tested three mathematical models of network evolution against their observations as a way to gain insights into what actually happened to interactions among genes over the evolutionary history of the yeast. In the first model, which they called uniform loss, interactions were lost at random. In the second model, called the poor-get-poorer model, the probability of loss of an interaction between two genes was set to be inversely proportional to number of ancestral interactions retained. The third, co-loss model, in which the probability of an interaction loss depends on number of shared neighboring genes (the more shared, the less likely a loss) proved to provide the best approximation to which interactions actually were lost and retained over time. The strength of the third model supported the authors' speculation that the partitioned networks originally formed through the partial loss of old function rather than the development of new functions, in contrast to the common belief that increased complexity is largely the consequence of positive selection.

After a genome duplication event, which provides networks with many simultaneously duplicated genes (nodes), the number of nodes in the network has doubled and the number of interactions has quadrupled. The subsequent gain or loss of interactions reduces redundancy.

What does evolution do when handed a spare set of genes? In the case of S. cerevisiae, at least, it appears to have modified interactions among genes and other cellular components to produce a set of partially independent daughter networks from each single ancient network, creating in the process a division of labor that makes the most of the possibilities presented by the fortuitous duplication of the genome in the yeast's ancient past.

Evolutionary biology research techniques predict cancer

Mon, 27 Mar 2006 01:25:37 PST

( from http://www.rxpgnews.com ) In diverse ecosystems, packed with wildly different species, evolution whizzes along. As different species accumulate mutations, some adapt particularly well to their environment and prosper. It happens in marine sediments, mountain forests and, as a new study illustrates, in precancerous tumors, too.

In a study published online today in Nature Genetics, Carlo Maley, Ph.D., a researcher at The Wistar Institute, and his colleagues report that precancerous tumors containing a population of highly diverse cells were more likely to evolve into cancer than those containing genetically similar cells. The finding suggests that, in at least some forms of cancer, the more genetically diverse a precancerous tumor is, the more likely that tumor is to progress to full-blown cancer. If so, genetic diversity might act as a biomarker for cancer risk among patients with precancerous tissues.

"Although researchers first defined cancer in evolutionary terms in the 1970s, few researchers have actually studied the disease this way," says Maley, lead author on the study and an assistant professor in the molecular and cellular oncogenesis program at Wistar. "We wanted to know: If we measured a precancerous tumor's genetic diversity at baseline, could we predict who would go on to get cancer?"

To find out, the scientists decided to analyze data on a precancerous condition called Barrett's esophagus, in which cells lining the lower esophagus change due to repeated exposure to stomach acid from reflux, a condition often referred to as heartburn. Doctors typically adopt a "wait and watch" approach to treating patients with Barrett's esophagus because the condition only rarely leads to cancer and is difficult to treat surgically.

In the study, Maley and colleagues analyzed precancerous tumor data from 268 patients, including multiple biopsies within each tumor. On average, these patients were followed for 4.4 years, during which time 37 developed cancerous tumors. Overall, the database used in the study represents more than 32,000 distinct genotypes of different cells within the tumors.

Using computational techniques to analyze the data, the researchers calculated measures of diversity inside the tumors. Essentially, they counted cell varieties and measured the genetic difference, or divergence, between those varieties. "Simply put, we took ecology measures of species diversity and translated them into measures of cell diversity within tumors," Maley says. The found a striking correlation between increased diversity of tumor cells and progression to cancer. For every additional cell variety detected in a tumor, the patient was twice as likely to progress to cancer.

Maley suggests that genetically diverse tumors have a high probability of generating mutant cells that will flourish and spread, allowing the tumor to transform and grow. In the future, in addition to serving as a biomarker for cancer risk, he adds, measures of genetic diversity might help doctors assess the success of cancer prevention therapies.

In fact, he speculates, genetic diversity among tumor cells might help explain why therapy sometimes fails. If a tumor contains a diverse population of cells, some of those cells are more likely to resist treatment, Maley says. Adapting to and surviving chemotherapy, these resistant cells could breed, leading to a cancer relapse. He hopes to pursue this hypothesis in the future. "More immediately," he adds, "we intend to validate the new study with other cohorts and other types of tumors."

Something fishy about human brain evolution?

Sun, 19 Feb 2006 17:16:37 PST

( from http://www.rxpgnews.com ) Forget the textbook story about tool use and language sparking the dramatic evolutionary growth of the human brain. Instead, imagine ancient hominid children chasing frogs. Not for fun, but for food.

According to Dr. Stephen Cunnane it was a rich and secure shore-based diet that fuelled and provided the essential nutrients to make our brains what they are today. Controversially, according to Dr. Cunnane our initial brain boost didn't happen by adaptation, but by exaptation, or chance.

"Anthropologists and evolutionary biologists usually point to things like the rise of language and tool making to explain the massive expansion of early hominid brains. But this is a Catch-22. Something had to start the process of brain expansion and I think it was early humans eating clams, frogs, bird eggs and fish from shoreline environments. This is what created the necessary physiological conditions for explosive brain growth," says Dr. Cunnane, a metabolic physiologist at the University of Sherbrooke in Sherbrooke, Quebec.

The evolutionary growth in hominid brain size remains a mystery and a major point of contention among anthropologists. Our brains weigh roughly twice as much as our similarly sized earliest human relative, Homo habilis two million years ago. The big question is which came first the bigger brain or the social, linguistic and tool-making skills we associate with it?

But, Dr. Cunnane argues that most anthropologists are ignorant or dismissive of the key missing link to help answer this question: the metabolic constraints that are critical for healthy human brain development today, and for its evolution.

Human brains aren't just comparatively big, they're hungry. The average newborn's brain consumes an amazing 75-per cent of an infant's daily energy needs. According to Dr. Cunnane, to fuel this neural demand, human babies are born with a built-in energy reservoir that cute baby fat. Human infants are the only primate babies born with excess fat. It accounts for about 14 per cent of their birth weight, similar to that of their brains.

It's this baby fat, says Dr. Cunnane, that provided the physiological winning conditions for hominids' evolutionary brain expansion. And how were hominid babies able to pack on the extra pounds? According to Cunnane their moms were dining on shoreline delicacies like clams and catfish.

"The shores gave us food security and higher nutrient density. My hypothesis is that to permit the brain to start to increase in size, the fittest early humans were those with the fattest infants," says Dr. Cunnane, author of the book Survival of the Fattest, published in 2005.

Unlike the prehistoric savannahs or forests, argues Dr. Cunnane, ancient shoreline environments provided a year-round, accessible and rich food supply. Such an environment was found in the wetlands and river and lake shorelines that dominated east Africa's prehistoric Rift Valley in which early humans evolved.

Dr. Cunnane points to the table scrap fossil evidence collected by his symposium co-organizer Dr. Kathy Stewart from the Canadian Museum of Nature, in Ottawa. Her study of fossil material excavated from numerous Homo habilis sites in eastern Africa revealed a bevy of chewed fish bones, particularly catfish.

More than just filling the larder, shorelines provided essential brain boosting nutrients and minerals that launched Homo sapiens brains past their primate peers, says Dr. Cunnane, the Canada Research Chair in Brain Metabolism and Aging.

Brain development and function requires ample supplies of a particular polyunsaturated fatty acid: docosahexaenoic acid (DHA). DHA is critical to proper neuron function. Human baby fat provides both an energy source for the rapidly growing infant grey matter, and also, says Dr. Cunnane, a greater concentration of DHA per pound than at any other time in life.

Aquatic foods are also rich in iodine, a key brain nutrient. Iodine is present in much lower amounts from terrestrial food sources such as mammals and plants.

It was this combination of abundant shoreline food and the "brain selective nutrients" that sparked the growth of the human brain, he says.

"Initially there wasn't selection for a larger brain," argues Dr. Cunnane. "The genetic possibility was there, but it remained silent until it was catalyzed by this shore-based diet."

Dr. Cunnane acknowledges that for the past 20 years he's been swimming upstream when it comes to convincing anthropologists of his position, especially that initial hominid brain expansion happened by chance rather than adaptation.

But, he says, the evidence of the importance of key shoreline nutrients to brain development is still with us painfully so. Iodine deficiency is the world's leading nutrient deficiency. It affects more than a 1.5 billion people, mostly in inland areas, and causes sub-optimal brain function. Iodine is legally required to be added to salt in more than 100 countries.

Says Dr. Cunnane: "We've created an artificial shore-based food supply in our salt."

Fish have menopause, study determines

Thu, 29 Dec 2005 16:18:38 PST

( from http://www.rxpgnews.com ) A UC Riverside-led research team has found that as some populations of an organism evolve a longer lifespan, they do so by increasing only that segment of the lifespan that contributes to "fitness" the relative ability of an individual to contribute offspring to the next generation.

Focusing on guppies, small fresh-water fish biologists have studied for long, the researchers found that guppies living in environments with a large number of predators have adapted to reproduce earlier in life than guppies from low-predation localities. Moreover, when reproduction ceases, guppies from high-predation localities are far older, on average, than guppies from low-predation localities, indicating that high-predation guppies enjoy a long "reproductive period" the time between first and last reproduction.

"In earlier work, we showed that guppies from high predation environments have longer lifespans," said David Reznick, professor of biology. "Our new study explores how and why this happens. We found that fish from populations enjoying longer lifespans live longer because there is a selective increase in their reproductive lifespan. Indeed, theory predicts this result because only reproductive lifespan determines fitness."

Study results appear Dec. 27 in the online edition of the Public Library of Science Biology.

The study supports the controversial hypothesis that natural selection the process in nature by which only organisms best adapted to their environment tend to survive and pass on their genetic characters in increasing numbers to succeeding generations introduces changes in only a specific segment of an organism's lifespan.

The researchers conducted their experiments by comparing life-history traits in 240 guppies they retrieved from high- and low-predation streams in mountains in Trinidad. In their analysis, they divided the life history into three non-overlapping segments: the age at maturity (birth to first reproduction), the reproductive lifespan (first to last reproduction) and the post-reproductive lifespan (last reproduction to death). They also devised a statistical criterion for evaluating whether or not guppies had a post-reproductive lifespan, that is, did guppies live significantly past the end of their capacity to reproduce?

"We were exploring whether or not fish have the equivalent of mammalian menopause," Reznick said. "We found that 60 percent of the fish had a significant post-reproductive lifespan, indicating that, yes, fish do have menopause. Indeed, their patterns of growing old are similar to those of mammals."

The researchers' statistical analysis also showed that regardless of which environments the guppies lived in, there were no differences among their populations in the probability of having a post-reproductive lifespan or in its duration.

"This is just what one might predict because these fish provide no care for their young," explained Reznick. "The older fish, after they stop reproducing, do not contribute to the fitness of young fish. As a result, the post-reproductive period is not influenced by natural selection. This result could be of interest to those who study menopause in humans and who have argued that post-reproductive humans can increase their own fitness by contributing to the fitness of their grandchildren and that the prolonged post-reproductive lifespan of humans is, therefore, the product of natural selection.

"But such arguments are difficult to prove by working on a single population or species. Nevertheless, our results show how it would be possible to evaluate whether or not menopause in humans has been shaped by natural selection. Appropriate comparisons, such as those between humans and apes, would help."

Modeling the Origin and Spread of Early Agriculture

Thu, 29 Dec 2005 16:01:38 PST

( from http://www.rxpgnews.com ) After the last major ice age some 10,000 years ago, things began to look up for early humans. Forbidding climes yielded to more hospitable weather patterns, and people began to settle down and domesticate plants and animals. Archeologist Gordon Childe, who in 1942 called the transition from hunting and gathering to agriculture the Neolithic Revolution, proposed that unchecked population growth triggered economic and social problems among Near Eastern populations and forced farmers and shepherds to search for new lands. In this demic diffusion model, dispersing populations introduced Europeans to the Neolithic lifestyle. Alternately, Europeans may have learned to farm by imitating Neolithic practitioners they encountered through trade or other interactions (the cultural diffusion model).

Childe's ideas of westward migration found support in a 1965 study that mapped the spatiotemporal pattern of a small sample of radiocarbon dates (determined from animal bones and other carbon remains) from Neolithic sites. A landmark study by Albert Ammerman and Luigi Cavalli-Sforza in 1971 used more dataradiocarbon dates from 53 early Neolithic sitesand used a population biology model to investigate Neolithic spread. Their wave of advance model proposed that population growth at the agricultural fringes coupled with local migrations would produce steady population expansions in all directions. They calculated an average rate of spread of about one kilometer per year.

But the controversy between the cultural and demic diffusion models still remains today. Now, over 30 years later, Ron Pinhasi and Joaquim Fort revisited the question along with Ammerman, using a substantially larger dataset with new locationsradiocarbon-dated bones and charcoal from 735 Neolithic sites in Europe, the Near East, and Asiaand reaffirm the wave-of-advance model. The authors combined mathematical and geospatial techniques to estimate the timing and likely center of agricultural origins, as well as the rate of spread. Their results support a model of demic diffusion and, for the first time, pinpoint the geographic origin of agriculture within the Fertile Crescent.

Pinhasi et al. calculated the correlation between the straight distance versus age of the 735 radiocarbon dates and the likely spread from 25 hypothetical centers of origin (based on location only) and ten probable centers (sites that included the oldest remains, as well as a center proposed in the 1971 study). The most southern point, Abu Madi in Egypt, had the highest correlation, though eight of the other probable centers had similar scores. However, charting the shortest paths (which take into account the barrier effect of the Mediterranean Sea), pointed to an origin in the north. Focusing on the centers that seemed most likely, Pinhasi et al. used both approaches (one based on straight paths, one based on shortest paths) to estimate the speed of agricultural spread, and came up with nearly the same figure: 0.71.1 kilometers per year versus 0.81.3 kilometers per year. An error range for this speed was estimated (which had not been done before), so the authors could also compare this observed rate with that predicted by a model.

While no cultural diffusion model is known so far that can explain the observed rate (calculated from the archeological evidence), a kilometer or so a year is consistent with a time-delayed demic diffusion model. (This model, which was proposed by Fort and co-workers in 1999, also agrees with data from other human and nonhuman population expansions, as well as with the observed speeds of virus infections.) While many genetic studies also support demic diffusion, they do not agree on the extent to which Near Eastern farmers contributed to the European gene pool. Assuming a linear advance, agricultural expansion began some 9,00011,500 years ago, falling in line with a gradual wave of advance. Rather than racing across the map of Europe, the authors argue, the Neolithic transition took over 3,000 years, or 100 generations, reflecting the time children stay with their parents before moving on to greener pastures. This is precisely the time-delay effect that classical diffusion models are unable to capture, but that is accounted for in the model by Fort and co-workers. Finally, the authors incorporated radiocarbon data from 30 sites in Arabia to find the most likely birthplace of agriculture. Their shortest-path analysis points to northern Levant and northern Mesopotamia (whereas the straight-path, or classical, approach pointed to a southern origin).

The authors' approach did not address whether migrants traveled by land or by sea or whether farmers displaced foragers. But the pattern and processes of dispersal were likely complex, Pinhasi et al. conclude, with multiple paths and mechanisms fueling the western expansion of the Neolithic lifestyle. And with a newly bolstered wave-of-advance model and the approach outlined here, geneticists, anthropologists, and other researchers investigating the origin and spread of human populations have a more detailed roadmap to follow.

Dancing ability determines mate quality

Thu, 22 Dec 2005 05:10:38 PST

( from http://www.rxpgnews.com ) Dance has long been recognized as a signal of courtship in many animal species, including humans. Better dancers presumably attract more mates, or a more desirable mate.

What's seemingly obvious in everyday life, however, has not always been rigorously verified by science. Now, a study by scientists at Rutgers, The State University of New Jersey, for the first time links dancing ability to established measures of mate quality in humans.

Reporting in Thursday's edition of the British science journal Nature, Rutgers anthropologists collaborating with University of Washington computer scientists describe how they created computer-animated figures that duplicated the movements of 183 Jamaican teenagers dancing to popular music. The researchers then asked peers of the dancers to evaluate the dancing ability of these animated figures. The figures were gender-neutral, faceless and the same size all to keep evaluators from boosting or dropping dancers' scores based on considerations other than dance moves.

The researchers also evaluated each dancer for body symmetry, an accepted indicator in most animal species including humans of how well an organism develops despite problems it encounters as it matures. Symmetry, and its association with attractiveness, therefore indicates an organism's underlying quality as a potential mate. The study showed that higher-rated dancers were typically people with greater body symmetry.

"At least since Darwin, scientists have suspected that dance so often plays a role in courtship because dance quality tracks with mate quality," said Lee Cronk, associate professor of anthropology. "But this has been hard to study because of the difficulty of isolating dance movements from variables, such as attractiveness, clothing and body features. By using motion-capture technology commonly employed in medical and sports science to isolate dance movements, we can confidently peg dancing ability to desirability."

Cronk and postdoctoral research fellow William Brown also examined results by the sex of the dancer. They found that symmetric males received better dance scores than symmetric females and that female evaluators rated symmetric men higher than male evaluators rated symmetric men.

"In species where fathers invest less than mothers in their offspring, females tend to be more selective in mate choice and males therefore invest more in courtship display," Brown said. "Our results with human subjects correlate with that expectation. More symmetrical men put on a better show, and women notice."

The researchers worked with a group of Jamaicans, building on earlier studies of physical symmetry in that population. The test group was ideal for a scientific study of dance, since in Jamaican society, dancing is important in the lives of both sexes. The dancers ranged in age from 14 through 19, and each danced to the same song, popular at the time in Jamaican youth culture. The researchers affixed infrared reflectors on 41 body locations of each dancer, from head-to-toe and arm-to-arm, to capture and measure detailed body movements. They fed data into programs that first created dancing animations of stick figures and then converted those animations into virtual human forms.

How sense of smell affects mating and aggression

Thu, 22 Dec 2005 03:41:38 PST

( from http://www.rxpgnews.com ) New research by scientists at UCSF sheds light on how the odor detecting system in mice sends signals that affect their social behavior.

"Understanding how mice process cues from the olfactory system--which regulates the sense of smell--should provide insight into the fundamental principles that mammalian brains use to transform sensory information into behavior," says lead investigator Nirao Shah, MD, PhD, UCSF assistant professor of anatomy.

"There are striking genetic and neuroanatomic similarities between mice and humans. We hope that such basic knowledge of how the brain functions will eventually be useful in understanding how the human brain generates behaviors in humans," he adds.

The UCSF study focused on the sexual and aggressive behaviors triggered by the rodent's olfactory system. The findings are published in the December issue of Nature Neuroscience.

According to Shah, researchers traditionally have thought rodents detect pheromones through a specialized organ--the vomeronasal organ (VNO) in the nose--that is separate from the main olfactory system. Pheromones are olfactory cues that signal the social and sexual status of individuals of a species, and their detection is a key step in regulating behaviors such as mating and aggression.

The new study findings show, however, that male mice require intact functioning of the main olfactory epithelium (MOE) in order to detect pheromones that elicit sexual behavior and fighting. The MOE covers the olfactory region of the nasal cavity and contains sensory neurons that recognize odors and transmit this information to the brain.

The study is important, says Shah, because it establishes a novel and hitherto unsuspected role for the MOE in regulating mating and aggressive behavior in mice. He adds that while it appears humans do not have an intact VNO, they do possess a functioning MOE.

In the study, researchers compared the behavior of mutant male mice that had been genetically modified to disrupt the functioning of their MOE with the behavior of normal mice, also known as wild-type mice. Wild-type female and male mice were placed at separate times in cages with the male mutants.

When comparing the mutant males with wild-type males, study results showed that all wild-type males mated with test females, while none of the mutants engaged in sexual behavior with the females. "Typically, when you take a female and put her in a cage, the male will initially sniff her, a process known as chemoinvestigation, and then mate with her," Shah says. "But the mutants without the MOE even showed a profound defect in initiating chemoinvestigation of the test females."

When a wild-type male encounters another male, he will typically sniff the male and then initiate a fight. However, the mutant males were defective in sniffing the test wild-type males, and they did not attack the wild-type males, Shah notes. "This suggests a broad and essential role for the MOE in regulating mating and aggression."

More research is needed to understand the role of the olfactory system and human behavior, but clearly this is an important connection for people, according to Shah. "The booming perfume industry attests to our belief that odors can attract potential suitors, and there are some studies in humans that suggest pheromone-type signals might have subtle effects on the regulation of certain physiological functions, such as the menstrual cycle."

Stimulation of the other senses also has a direct effect on behavior, he adds. "When you touch a hot pan, you immediately draw your hand away. Or, if you place your finger in an infant's palm, the baby will grasp it instinctively."

The current research findings might also be relevant for controlling pest populations, which utilize olfactory cues in a manner similar to mice, according to Shah.

Dog Genome Sheds Light on Human Evolution

Thu, 08 Dec 2005 18:37:38 PST

( from http://www.rxpgnews.com ) An international research team led by scientists at the Broad Institute of MIT and Harvard announced today the completion of a high-quality genome sequence of the domestic dog, together with a catalogue of 2.5 million specific genetic differences across several dog breeds. Published in the December 8 issue of Nature, the dog research sheds light on both the genetic similarities between dogs and humans and the genetic differences between dog breeds.

Comparison of the dog and human DNA reveals key secrets about the regulation of the master genes that control embryonic development. Comparison among dogs also reveals the structure of genetic variation among breeds, which can now be used to unlock the basis of physical and behavioural differences, as well the genetic underpinnings of diseases common to domestic dogs and their human companions.

"Of the more than 5,500 mammals living today, dogs are arguably the most remarkable," said senior author Eric Lander, director of the Broad Institute, professor of biology at MIT and systems biology at Harvard Medical School, and a member of the Whitehead Institute for Biomedical Research. "The incredible physical and behavioural diversity of dogs -- from Chihuahuas to Great Danes is encoded in their genomes. It can uniquely help us understand embryonic development, neurobiology, human disease and the basis of evolution."

Dogs not only occupy a special place in human hearts, they also sit at a key branch point in the evolutionary tree relative to humans. By tracking evolution's genetic footprints through the dog, human and mouse genomes, the scientists found that humans share more of their ancestral DNA with dogs than with mice, confirming the utility of dog genetics for understanding human disease.

Most importantly, the comparison revealed the regions of the human genome that are most highly preserved across mammals. "The clustering of regulatory sequences is incredibly interesting," said Kerstin Lindblad-Toh, first author of the Nature paper and co-director of the genome sequencing and analysis program at Broad.

Dogs were domesticated from gray wolves as long as 100,000 years ago, but selective breeding over the past few centuries has made modern dog breeds a testament to biological diversity. Efforts to create the genetic tools needed to map important genes in dogs have gained momentum over the last 15 years, and already include a partial survey of the poodle genome. First, they acquired high-quality DNA sequence from a female boxer named "Tasha," covering nearly 99% of the dog's genome. By comparing these dogs, they pinpointed ~2.5 million individual genetic differences among breeds, called single nucleotide polymorphisms (SNPs), which serve as recognizable signposts that can be used to locate the genetic contributions to physical and behavioural traits, as well as disease.

Finally, the scientists used the SNP map to reconstruct how intense dog breeding has shaped the genome. They discovered that selective breeding carried large genomic regions of several million bases of DNA into breeds, creating 'haplotype blocks' that are ~100 times larger than seen in the human population. "The huge genomic regions should make it much easier to find the genes responsible for differences in body size, behaviour and disease," said Lander. "Such studies will need many fewer markers than for human studies.
Breeding programs not only selected for desired traits, they also had the unintended consequence of predisposing many dog breeds to genetic diseases, including heart disease, cancer, blindness, cataracts, epilepsy, hip dysplasia and deafness. With the dog genome sequence and the SNP map, scientists around the world now have the tools to identify these disease genes.

Tasha, the boxer from which the DNA for sequencing the dog genome was taken

"The genetic contributions to many common diseases appear to be easier to uncover in dogs," said Lindblad-Toh. "If so, it is a significant step forward in understanding the roots of genetic disease in both dogs and humans."

For this work, the dog-owner community is an essential collaborator. "We deeply appreciate the generous cooperation of individual dog owners and breeders, breed clubs and veterinary schools in providing blood samples for genetic analysis and disease gene mapping," said Lindblad-Toh.

Gene regulation changes had major impacts on human evolution

Tue, 15 Nov 2005 19:49:38 PST

( from http://www.rxpgnews.com ) With humans and chimpanzees differing by just 1.2% at the DNA level, it's clear that our differences do not arise from gene variation alone. Thirty years ago, Mary-Claire King and Alan Wilson pointed to our extensive protein similarities as evidence that those investigating the genetic basis of human origins should focus on the regulators of gene expression rather than on the genes themselves.

DNA sequences that regulate gene expression, called cis-regulatory elements, occur on the same DNA molecule as the regulated gene. By recruiting proteins that initiate or block transcription, cis-regulatory elements influence the rate at which genes are transcribed, in which cells, and under what conditions. But since sequence inspection doesn't reveal whether regulatory sequence changes are functional or neutral, finding evidence for human-specific changes and positive selection in these sequences is far harder than finding similar evidence in protein sequences or in gene sets. Now, Matthew Rockman, Gregory Wray, and their colleagues provide further support for King and Wilson's predictions by showing that positive selection altered the cis-regulation of a gene expressed in the human brain.

To find evidence of regulatory changes underlying uniquely human traits, Rockman et al. examined the regulatory evolution of prodynorphin, a gene expressed in multiple brain and endocrine cell types. The protein encoded by prodynorphin is a precursor molecule for a suite of neuropeptides that bind to opiate receptors and affect perception, pain sensation, emotion, and learning. In humans, prodynorphin's promoter contains what's called a 68 base-pair tandem repeat polymorphismâindividuals can have up to four copies of the 68 DNA base-pair element, which occur side by side. The polymorphism, which affects how many transcripts of the gene are produced, has been tentatively linked to schizophrenia, cocaine addiction, and epilepsy.

To explore how this functional variation evolved, Rockman et al. first sequenced and analyzed prodynorphin regulatory DNA from 74 human chromosomes and 32 nonhuman primate chromosomes (chimp, bonobo, gorilla, orangutan, baboon, and two macaque species). The duplication leading to tandem repeats appears unique to humans, since all the monkeys and other great apes carry only one copy of the 68 base-pair element. Further distinguishing humans from the last common ancestor of humans and chimps, the human copies also carry five mutations, or substitutions, far more than would be expected if the mutations were neutral (that is, had no effect on fitness). Three nearby polymorphisms also occurred at a higher-than-expected frequency in humans, a sign that selection acted on the linked neighboring sequences. The protein-coding sequence of prodynorphin, on the other hand, appears to have undergone negative selection, discarding harmful mutations that would disrupt its function.

To determine the functional effects of the human substitution, the authors attached a bioluminescent enzyme to human and chimp prodynorphin cis-regulatory DNA, and introduced the modified DNA into human cell lines so they could measure transcription levels. Only the human 68 base-pair element significantly increased transcription of prodynorphin, and this increase was seen only in brain cells.

Because different numbers of repeats are associated with different effects, such as protection against cocaine addiction and neurological disease, Rockman et al. searched for signs of recent selection. If selection had occurred, divergence among populations should be increased and variation within populations reduced, relative to the neutral case. And that's what the authors found. The frequency of three-repeat versions of the 68 base-pair element was less than 10% in Chinese and Papua New Guinean populations and over 60% in Italy and Ethiopia. And variation at genome markers called microsatellites was significantly low overall across most of the populations studied (which also included India). Because microsatellites typically undergo high mutation rates, if a microsatellite is linked to an element under positive selection, it should show reduced variation.

The observed pattern of variations within and among human populations, the authors argue, suggests that recent selection has favored different versions of prodynorphin-regulatory elements in different regions of the world. These results support the longstanding notion that changes in gene regulation had major impacts on the evolution of novel traits, and may well hold the key to that eternal question, what makes us human? âLiza Gross

Brain is broadly wired for reproduction

Sat, 12 Nov 2005 20:48:38 PST

( from http://www.rxpgnews.com ) Howard Hughes Medical Institute researchers have discovered a vast network of neurons in the brain of mice that governs reproduction and controls the effects of reproductive status on other brain functions.

In their studies, the researchers found neural circuits that coordinate a complex interplay between neurons that control reproduction and brain areas that carry the neural signals triggered by odorant molecules and those triggered by pheromones, chemical signals produced by animals. The researchers characterize their findings as an initial step in understanding the far-reaching influence that odors and pheromones may have on reproduction and other behaviors.

The research team, which was led by HHMI investigator Linda B. Buck at the Fred Hutchinson Cancer Research Center, included first author Ulrich Boehm and Zhihua Zou, who did the work as postdoctoral fellows while in Buck's lab. The researchers published their studies in an immediate early publication on November 10, 2005, in the journal Cell. Related studies by HHMI investigator Catherine Dulac are published in the same issue.

The scientists began their studies by focusing on tracing the neural pathways leading to and from neurons that produce gonadotropin releasing hormone (GnRH), which is also known as luteinizing hormone releasing hormone (LHRH). These neurons regulate sexual physiology -- including onset of puberty, ovulation, and the menstrual cycle in females and testosterone production in males -- by regulating the release of hormones from the pituitary gland. Interestingly, GnRH neurons also appear to be involved in the control of sexual behaviors.

"Consistent with the idea that GnRH neurons might have additional functions beyond controlling the pituitary, other investigators have shown that GnRH axons can be found in many different areas of the brain," said Buck. "Those findings suggested that GnRH neurons were sending signals to other neurons, but the neurons that received the signals were unknown. Even more importantly for us, though certain brain areas had been implicated in pheromone signaling, specific neurons that transmit pheromone signals to GnRH neurons had not been identified."

To map the neural circuits involving GnRH neurons, the researchers used a genetic tracing method that they previously developed for charting neural pathways. They first engineered mice in which GnRH neurons produce barley lectin (BL), a tracer molecule that travels upstream and downstream to connected neurons, and green fluorescent protein (GFP), to mark the producing cells. By visualizing the locations of BL, GFP, and GnRH neurons and their axons, the researchers were able to identify neurons directly connected to GnRH neurons. They also determined which neurons sent signals to GnRH neurons and which neurons received signals from GnRH neurons.

These studies revealed that connections go in both directions between GnRH neurons and relay stations in the brain that process signals from both the olfactory and vomeronasal systems, said Buck.

In mice and other mammals, the olfactory and vomeronasal systems are distinct pathways for sensing chemicals in the environment. While the main olfactory system that begins in the nose processes odors, the vomeronasal (accessory) system receives signals -- triggered by pheromones -- from the vomeronasal organ (VNO) in the nasal septum. However, the systems are not entirely parallel. Buck and her colleagues have shown that the VNO can detect some odorants. And conversely, there is evidence that some pheromone signals require input from the nose in addition to the VNO.

"Our findings suggest that both odor and pheromone relay areas in the brain are sending pheromone signals to GnRH neurons. Moreover, GnRH neurons, in turn, are sending information back to those relay areas," said Buck. "This surprising finding suggests that the GnRH neurons are influencing the processing of odor and pheromone signals in the brain. It may be the brain's way of saying whether or not it wants to receive particular sensory information -- depending on the reproductive circumstances, such as the stage of the female's estrus cycle."

The researchers also sought to determine whether pheromones could trigger olfactory pathways to activate GnRH neurons. To investigate this, they exposed male and female mice, respectively, to female or male sex-related pheromones and measured how neurons that are connected to GnRH neurons reacted. They also exposed the males to clean bedding, which was thought to be a neutral stimulus.

They found that pheromones triggered responses in neurons upstream of GnRH neurons in both odor and pheromone relay areas. "This suggests that there is a redundancy in pheromone detection, with at least some pheromone information being conveyed by both the main and accessory systems," said Buck. "This redundancy is not too surprising, if you consider how important it is to the animal to be able to sense pheromones. The redundancy might guard against the loss of a pheromone receptor from either the VNO or the olfactory epithelium causing a devastating loss of pheromone detection."

The studies showed that the odor of clean bedding also activated some neurons upstream of GnRH neurons. "This suggests that the animal's environment could also influence GnRH neurons, perhaps signaling whether the animal is in the optimal environment for mating." Buck said.

In tracing the connections between GnRH neurons and neurons throughout the brain, Boehm and his colleagues soon found that they had undertaken an enormous task to figure out these connections. "We were really shocked with what we found," Buck said. "We found that, although the GnRH neurons number only about eight hundred in mice, they connect directly with about fifty thousand other neurons. And these neurons are in brain areas involved in a wide array of functions -- for example, appetite, feeding, reward, arousal, and the relay of information to higher brain areas that control cognitive function. I don't think anyone ever suspected this complexity. It reveals that GnRH neurons are master integrators of information about the external environment, as well as the internal state of the animal."

The studies also suggest that GnRH neurons influence a wide array of brain functions, possibly coordinating those functions with neuroendocrine status in order to optimize reproductive success, according to Buck.

Almost all the GnRH neuron-connected areas were identical in male and female mouse brains. However, there were some telltale sex differences in the circuitry, which offer important new pathways for investigating differences in male and female reproductive physiology and behavior, Buck said.

Although it is still early, the researchers suspect that the findings in mice could have implications for humans. "Because humans don't have a vomeronasal system, many have speculated that they may not detect pheromones," Buck said. "But these studies clearly indicate that the main olfactory system, which humans do have, is capable of transmitting pheromone signals. Therefore, if there are human pheromones -- although no one has yet identified one -- they would presumably transmit their signals through the main olfactory pathway."

Although the findings are considered a first step in exploring the GnRH reproduction-related circuitry in the brain, Buck acknowledges that they have already learned a great deal just by defining the circuits. "These findings now set the stage for studies in which the neurons in those circuits can be analyzed to determine the genes they selectively express. Then those genes can be used -- for example in gene knockout studies -- to determine what role the neurons play in reproduction and behavior," Buck said.

"Understanding how the brain's neural circuitry controls behavior has been largely a black box," she said. "I think that through studies like these we and others are going to make substantial progress in understanding the neural circuits that underlie behavior."

Oestrogen Levels Translate Into Facial Attractiveness

Wed, 02 Nov 2005 22:21:38 PST

( from http://www.rxpgnews.com ) Scientists have found that a womans hormones relate to how attractive she is. The researchers at the University of St Andrews, found that women with higher levels of the female sex hormone, oestrogen, have more attractive looking faces.

The new study, led by psychologist Miriam Law Smith, could explain the underlying reason why men prefer women with feminine faces. It is the first study to demonstrate that womens facial appearance is linked to their underlying health because oestrogen is the hormone which impacts on womens reproductive health and fertility. These effects on appearance are likely to depend on the action of oestrogen throughout puberty.

Law Smith and a team of psychologists at the Universitys Perception Lab photographed 59 young womens faces aged between 18 and 25 and analysed their sex hormone levels. Women with higher levels of oestrogen were rated as more attractive, healthy and feminine looking than those with lower levels.

Composite faces of the 10 women with highest (left) and 10 with lowest (right) levels of oestrogen. Credit: www.perceptionlab.com

Interestingly, no relationship between appearance and oestrogen was found in women wearing make-up. Researchers believe that while make-up improves facial appearance it may be masking cues normally seen in the face.

Law Smith said: Women are effectively advertising their general fertility with their faces. Our findings could explain why men universally seem to prefer feminine womens faces. In evolutionary terms, it makes sense for men to favour feminine fertile women, those that did would have had more babies.

Lightning-fast Evolution Driven By Picky Female Frogs

Sun, 30 Oct 2005 14:21:38 PST

( from http://www.rxpgnews.com ) Picky female frogs in a tiny rainforest outpost of Australia have driven the evolution of a new species in 8,000 years or less, according to scientists from the University of Queensland, the University of California, Berkeley, and the Queensland Parks and Wildlife Service.

"That's lightning-fast," said co-author Craig Moritz, professor of integrative biology at UC Berkeley and director of the Museum of Vertebrate Zoology. The yet-to-be- named species arose after two isolated populations of the green-eyed tree frog reestablished contact less than 8,000 years ago and found that their hybrid offspring were less viable. To avoid hybridizing with the wrong frogs and ensure healthy offspring, one group of females preferentially chose mates from their own lineage. Over several thousand years, this behavior created a reproductively isolated population - essentially a new species - that is unable to mate with either of the original frog populations.

This example suggests that rapid speciation is often driven by recontact between long-isolated populations, Moritz said. Random drift between isolated populations can produce small variations over millions of years, whereas recontact can amplify the difference over several thousands of years to generate a distinct species.

"The overarching question is: Why are there so many species in the tropics?" Moritz said. Moritz; lead author Conrad Hoskin, a graduate student at the University of Queensland in St. Lucia, Australia; and colleagues Megan Higgie of the University of Queensland and Keith McDonald of the Queensland Parks and Wildlife Service, reported their findings in the Oct. 27 issue of Nature.

The green-eyed tree frog, Litoria genimaculata, lives in the Wet Tropics area of northeast Queensland, a rugged tropical region of Australia along the Pacific Ocean's Great Barrier Reef. The frog, which is green with reddish-brown splotches, is common around streams and grows to about 2 1/2 inches in length.

Because of geographic isolation that began between 1 and 2 million years ago with the retreat of rainforest to higher elevations, two separate frog lineages developed in the northern and southern parts of the species' coastal range - only to be reconnected less than 8,000 years ago as the climate got wetter and warmer and the rainforest expanded.

Hoskin and his colleagues found that the northern and southern calls of the male frog, which are what females pay attention to in the mating game, had become different from each other. Yet despite this difference, reflected in the call's duration, note rate and dominant frequency, the two lineages could still breed with one another.

The southern females, however, were more picky about their mates than the northern females. And in one area of contact that had become isolated from the southern range, the southern females were extremely picky, to the extent that they almost never mated with northern males.

In laboratory breeding experiments, the biologists discovered the reason for this choosiness: While northern and southern lineages could breed successfully, they apparently had diverged enough during their million-year separation that offspring of southern females and northern males failed to develop beyond the tadpole stage. Though crosses involving northern females and southern males successfully produced frogs, the offspring developed more slowly than the offspring of pairs of northern frogs.

Field studies confirmed the laboratory results. Researchers could find no hybrid frogs in the contact zones that were the offspring of southern mothers, judging by the absence of any southern mitochondrial DNA, which is contributed only by the mother.

Green-eyed tree frogs live along streams in the Wet Tropics region of Queensland, on the northeast coast of Australia. (Photo courtesy: Conrad Hoskin)

Hoskin and colleagues argue that because southern females have the most to lose in such cross-breeding, there may have been selection pressure to evolve a mating strategy to minimize dead-end mating with northern males. This appears to have occurred in the contact region where a population of the southern lineage had become isolated from the rest of its lineage and had developed a preference for certain male calls. The male frog call in this population has diverged significantly from both the northern and southern lineage calls.

"If females have a reason not to get the mating wrong, and they have some way of telling the males apart - the call - the theory is that this should create evolutionary pressure for the female choice to evolve so that they pick the right males," Moritz said.

"Reinforcement does not appear to occur at the more 'classic' contact between northern and southern lineages, and we speculate that this may be due to gene flow from the extensive range of the southern lineage into the contact zone," Hoskin said. "This problem does not exist at the other contact because the southern lineage population is very small and occurs primarily within the contact zone."

Because the frogs in the isolated contact area had a distinctively different call, and because they were effectively isolated from surrounding populations by mating preference, Hoskin and colleagues concluded that female choice led to this new species.

Interestingly, evolutionary theory would predict that the southern and northern frog populations would drift apart into two distinct species. In the case of the green-eyed tree frog, Moritz said, a subpopulation of the southern species drifted away not only from the northern species, but also from the southern. Moritz noted that geographic isolation in this "dinky bit of rainforest in Australia" has split many species, and that reinforcement at zones of recontact may be generating other new species.

Flipped Genes Illuminate Human Evolution

Thu, 27 Oct 2005 00:27:38 PST

( from http://www.rxpgnews.com ) By comparing the human genome with that of the chimpanzee, man's closest living relative, researchers have discovered that chunks of similar DNA that have been flipped in orientation and reinserted into chromosomes are hundreds of times more common in primates than previously thought. These large structural changes in the genome, called inversions, may account for much of the evolutionary difference between the two species. They may also shed light on genetic changes that lead to human diseases.

Although humans and chimpanzees diverged from one another genetically about six million years ago, the DNA sequences of the two species are approximately 98 percent identical. Given the 2005 publication of the draft chimpanzee genome sequence, researchers can now readily identify the differences between the human and chimp genomes. These differences lend insight into how primates evolved, including traits specific to humans.

Instead of identifying sequence changes between the two genomes at the base-pair level, Scherer focused his research on large structural variations in chromosomes between humans and chimps, specifically genetic inversions.

Inversions can disrupt the expression of genes at the point where the chromosome breaks, as well as genes adjacent to breakpoints. "From a medical genetics perspective, there are probably hundreds of disease genes that have not yet been characterized," said Scherer. "The vast majority of disease gene discovery has been based on gene sequencing, but this is not a comprehensive view of chromosomes. We are using an evolutionary approach to identify mutations that may predispose people to disease."

According to Scherer, prior to this research, only nine inversions between humans and chimps had been identified. Using a computational approach, Scherer's group identified 1,576 presumed inversions between the two species, 33 of which span regions larger than 100,000 base pairs--a sizeable chunk of DNA. The average human gene is smaller, only about 60,000 bases in length.

Scherer's team experimentally confirmed 23 out of 27 inversions tested so far. Moreover, by comparing the chimp genome with its ancestor, the gorilla genome, they determined that more than half of the validated inversions flipped sometime during human evolution.

Perhaps even more interesting than the abundance of inversions that Scherer's group unveiled was their discovery that a subset of the inversions are polymorphic--taking different forms--within humans, meaning that the human genome is still evolving. When the 23 experimentally confirmed inversions were tested against a panel of human samples, the scientists found three inversions with two alleles or pairs of genes displaying the human inversion in some people, whereas others had one allele of the human inverted sequence and one allele of the normal sequence in chimps.

Having one allele with an inversion and one allele without represents a ticking time bomb in genetic terms, Scherer said, since these alleles may improperly align and recombine during replication, ultimately causing DNA deletions or a loss of DNA that subsequent generations inherit. Scherer's prior research on Williams-Beuren syndrome, a disease caused by DNA micro-deletions, identified a significantly higher incidence of inversions among the parents of afflicted patients.

Interestingly, one of the inversions that Scherer identified as polymorphic in his current paper includes a gene known to be involved in colorectal cancer. Whether individuals polymorphic for this inversion are at increased risk for the development of colorectal cancer is not yet known.

Scherer said that his group looked at only a very small subset of the human population when assessing the prevalence of polymorphisms. He suspects that polymorphisms, and structural variations in general, may be much more common than his preliminary analyses suggest.

"These findings may cause people to rethink their ideas about how species evolved," Scherer said. "They also highlight how the mechanisms of evolution may be associated with disease."

Scherer determined that about 10 percent of the presumed inversions either contain a complete gene within the flipped region, constitute a flipped region within a gene, or cause a breakpoint somewhere within a gene. These inversions represent prime targets for disease gene discovery, which Scherer's team is exploring further.

This research expands on a Nature paper published on September 1, 2005, by HHMI investigator Evan E. Eichler at the University of Washington. Eichler's group determined that novel duplications of genetic material within humans also significantly contribute to differences between the species.

The researchers published their findings in the October 28, 2005, issue of the journal Public Library of Science Genetics (PLoS Genetics). The paper was published early online. Senior author Stephen W. Scherer is a HHMI international research scholar, a senior scientist in the Genetics and Genomic Biology Program at the Hospital for Sick Children in Toronto, Canada, and an associate professor of molecular and medical genetics at the University of Toronto.

Role of divergent selection in evolution of female mating preferences

Wed, 26 Oct 2005 15:44:38 PST

( from http://www.rxpgnews.com ) In the evolutionary war of the sexes, females choose their mates while males fight for the right to inseminate. Darwin explained this widely observed phenomenon in terms of energy expenditure: whichever sex invests more to produce and rear offspring gets to choose. That lot typically falls to females, whose mating preferences have driven the evolution of secondary sex characteristics as diverse as the peacock's extravagant tail and the fiddler crab's outsized claw. Such preferences may also influence speciation by causing reproductive isolation, acting as a behavioral barrier to gene flow between populations in much the same way mountain ranges act as physical barriers. In both cases, isolated populations that once interbred can diverge into separate species.

The effect of sexual selection on speciation has been demonstrated in many different organisms, but it's not so clear which evolutionary mechanismsâgenetic drift or natural selectionâaccount for the initial shift in mating preferences that generate divergent sexual selection. Different mating preferences could arise as a by-product of chance events related to unique mutations (genetic drift) that produce arbitrary traits later modified by sexual selection, or as a side effect of changes in traits that arise as populations adapt differently to their local environments (divergent natural selection). If divergent selection affects female mating preferences (assuming that mating preference differences contribute to reproductive isolation), then separate populations that adapt to different environments should also diverge in mating preferences, while populations adapted to similar environments should not.

Working with the Australian fruit fly Drosophila serrata, Howard Rundle, Mark Blows, and their colleagues at the University of Queensland in Australia investigated the role of divergent selection in the evolution of female mating preferences. Mate choice in D. serrata is mediated by nonvolatile pheromones in the insect's outer cuticle, called cuticular hydrocarbons (CHCs). In past experiments, male CHCs had been shown to evolve rapidly in response to changes in selection (which is not surprising since they protect the fly against environmental vagaries), but the consequence for female mating preferences was not known.

To address the effect of divergent selection on the evolution of female mating preferences, the authors created different environments in the lab by raising four duplicate fly populations on three different food resourcesâwith yeast representing the ancestral lab environment (these flies have eaten yeast since the stock was established in 1998), and rice and corn representing two novel environments. Flies were raised for 22 months, then fed yeast for two generations to control for environmental effects, before both CHCs and female mating preferences were estimated for each of the 12 populations.

To estimate female mating preferences, a single female from one of the experimental populations was placed in a vial with two males from the ancestral stock population, providing standard males for comparison of preferences among the populations. An average of 106 trials were conducted for each of the populations. After females had mated with one of the two males, CHCs from the chosen and rejected males were extracted for analysis. Female mating preferences were then determined for each population by calculating sexual selection gradients that related the mating success of the males with their CHCs.

CHC profiles for all the flies revealed that nearly every CHC molecule had adapted to the novel environments, although CHC evolution was greater in females than in males. Surprisingly, however, the mating trials showed that female mating preferences had also diverged consistently among populations in correlation with their environment (preferences were similar among populations from the same environment, but differed among populations from different environments). This so-called parallel evolution, the authors argue, implicates divergent selection over drift in preference evolution because genetic drift is unlikely to produce a pattern of preference evolution that is predictable by environment.

Altogether, the authors conclude, this evolutionary experiment shows that mating preferences âcan evolve at least in part in correlation with the environment.â This result is consistent with the classic by-product model of speciation, in which new species arise as a side effect of divergent selection; in this case, mating preferences act as a premating isolation mechanism that arises along with the divergent environments. Interestingly, the authors found no correlation between the CHCs that adapted most and those for which female preferences changed. Teasing apart the relative contributions of natural and sexual selection in the evolution of CHCs and mating preferences may help shed light on the complicated relationship between trait and preference evolution in generalâand on the role that preference plays in the emergence of new species. âLiza Gross

Human Brain Is Still Evolving

Fri, 09 Sep 2005 18:07:38 PST

( from http://www.rxpgnews.com ) Howard Hughes Medical Institute researchers who have analyzed sequence variations in two genes that regulate brain size in human populations have found evidence that the human brain is still evolving. They speculate that if the human species continues to survive, the human brain may continue to evolve, driven by the pressures of natural selection. Their data suggest that major variants in these genes arose at roughly the same times as the origin of culture in human populations as well as the advent of agriculture and written language. The research team, which was led by Bruce T. Lahn, a Howard Hughes Medical Institute investigator at the University of Chicago, published its findings in two articles in the September 9, 2005, issue of the journal Science.

Their analyses focused on detecting sequence changes in two genes - Microcephalin and abnormal spindle-like microcephaly associated (ASPM) - across different human populations. In humans, mutations in either of these genes can render the gene nonfunctional and cause microcephaly - a clinical syndrome in which the brain develops to a much smaller size than normal.

In earlier studies of non-human primates and humans, Lahn and his colleagues determined that both Microcephalin and ASPM showed significant changes under the pressure of natural selection during the making of the human species. Our earlier studies showed that Microcephalin showed evidence of accelerated evolution along the entire primate lineage leading to humans, for the entire thirty to thirty-five million years that we sampled, he said. However, it seemed to have evolved slightly slower later on. By contrast, ASPM has evolved most rapidly in the last six million years of hominid evolution, after the divergence of humans and chimpanzees.

In order to identify sequence changes that occurred in Microcephalin and ASPM in the evolutionary lineage leading to humans, Lahn and his colleagues took the following approach: They determined the DNA sequences of the two genes among a large number of primate species and searched for sequence differences between humans and nonhuman primates. By doing statistical analysis on these sequence differences, they could demonstrate that the differences were due to natural selection that drove significant sequence changes in the lineage leading to humans. These changes accumulated presumably because they conferred some competitive advantage.

The evidence that Microcephalin and ASPM were evolving under strong natural selection in the lineage leading to humans led Lahn and his colleagues to consider exploring whether these two genes are still evolving under selection in modern human populations. In the earlier studies, we looked at differences that had already been set in the human genome, he said. The next logical question was to ask whether the same process is still going on today, given that these genes have been under such strong selective pressure, leading to the accumulation of advantageous changes in the human lineage. If that is the case, we reasoned we might be able to see variants within the human population that are rising in frequency due to positive selection, but haven't gone to completion yet.

The researchers first sequenced the two genes in an ethnically diverse selection of about 90 individuals. The researchers also sequenced the genes in the chimpanzee, to determine the ancestral state of polymorphisms in the genes and to assess the extent of human-chimpanzee divergence.

In each gene, the researchers found distinctive sets of polymorphisms, which are sequence differences between different individuals. Blocks of linked polymorphisms are called haplotypes, whereby each haplotype is, in essence, a distinct genetic variant of the gene. They found that they could further break the haplotypes down into related variants called haplogroups. Their analysis indicated that for each of the two genes, one haplogroup occurs at a frequency far higher than that expected by chance, indicating that natural selection has driven up the frequency of the haplogroup. They referred to the high-frequency haplogroup as haplogroup D.

When the researchers compared the ethnic groups in their sample for haplogroup D of ASPM, they found that it occurs more frequently in European and related populations, including Iberians, Basques, Russians, North Africans, Middle Easterners and South Asians. That haplogroup was found at a lower incidence in East Asians, sub-Saharan Africans and New World Indians. For Microcephalin, the researchers found that haplogroup D is more abundant in populations outside of Africa than in populations from sub-Saharan Africa.

To produce more informative statistical data on the frequency of haplotype D among population groups, the researchers applied their methods to a larger population sample of more than one thousand people. That analysis also showed the same distribution of haplogroups.

Their statistical analysis indicated that the Microcephalin haplogroup D appeared about 37,000 years ago, and the ASPM haplogroup D appeared about 5,800 years ago - both well after the emergence of modern humans about 200,000 years ago. In the case of Microcephalin, the origin of the new variant coincides with the emergence of culturally modern humans, said Lahn. And the ASPM new variant originated at a time that coincides with the spread of agriculture, settled cities, and the first record of written language. So, a major question is whether the coincidence between the genetic evolution that we see and the cultural evolution of humans was causative, or did they synergize with each other?

Lahn said that the geographic origin and circumstances surrounding the spread of the haplogroups can only be surmised at this point. One can make guesses, but our study doesn't reveal how these positively selected variants arrived," he said. "They may have arisen in Europe or the Middle East and spread more readily east and west due to human migrations, as opposed to south to Africa because of geographic barriers. Or, they could have arisen in Africa, and increased in frequency once early humans migrated out of Africa.

While the roles of Microcephalin and ASPM in regulating brain size suggest that the selective pressure on the new variants may relate to cognition, Lahn emphasized that this possibility remains speculative. What we can say is that our findings provide evidence that the human brain, the most important organ that distinguishes our species, is evolutionarily plastic, he said. Finding evidence of selection in two such genes is mutually reinforcing, he pointed out. Finding this effect in one gene could be anecdotal, but finding it in two genes would make it a trend. Here we have two microcephaly genes that show evidence of selection in the evolutionary history of the human species and that also show evidence of ongoing selection in humans.

Lahn emphasized that it would not be correct to interpret the findings as indicating that one ethnic group is more evolved than another. Any differences among groups would be minor compared to the large differences in such traits as intelligence within those groups, he said. We're talking about the average impact of such variants, he said. We still have to treat each individual as an individual. Just because you have one gene that makes you more likely to be a little taller, doesn't mean you will be tall, given the complex effect of all your other genes and of environment. Lahn also said that a multitude of other genes likely exist that influence brain size and development, and further research could reveal far more complex effects of natural selection on such genes.

Lahn speculated that the new findings suggest that the human brain will continue to evolve under the pressure of natural selection. Our studies indicate that the trend that is the defining characteristic of human evolution - the growth of brain size and complexity - is likely still going on. If our species survives for another million years or so, I would imagine that the brain by then would show significant structural differences from the human brain of today.

For both Microcephalin and ASPM, Lahn and his colleagues are trying to find out the precise traits that are under natural selection. They are also performing more detailed studies of the two genes in human populations to better understand their evolutionary history. And they are searching for other brain-related genes that have changed under the pressure of natural selection. We want to know how broad a trend these two genes represent, said Lahn. Did we get really lucky and hit on two rare examples of such genes? Or, are they representative of many other such genes throughout the genome. I would bet, though, that we will find evidence of selection in a lot more genes.

Multi-species genome comparison sheds new light on evolution

Sat, 23 Jul 2005 01:45:38 PST

( from http://www.rxpgnews.com ) An international team that includes researchers from the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), has discovered that mammalian chromosomes have evolved by breaking at specific sites rather than randomly as long thought and that many of the breakage hotspots are also involved in human cancer.

In a study published in the July 22 issue of the journal Science, a team of 25 scientists from the United States, France and Singapore compared the organization of the chromosomes of eight mammalian species: human, mouse, rat, cow, pig, dog, cat and horse. Using sophisticated computer software to align and compare the mammals' genetic material, or genomes, the team determined that chromosomes tend to break in the same places as species evolve, resulting in rearrangements of their DNA. Prior to the discovery of these breakage hotspots, the prevailing view among scientists was that such rearrangements occurred at random locations.

"This study shows the tremendous power of using multi-species genome comparisons to understand evolutionary processes, including those with potential relevance to human disease," said NHGRI Scientific Director Eric D. Green, M.D., Ph.D. "The dog genome map generated by NHGRI researchers and their collaborators played a key role in these new analyses. Furthermore, the team took full advantage of the wealth of human, mouse and rat genome sequence data generated by the recently completed Human Genome Project."

Chromosomes are the threadlike "packages" of DNA located in the nucleus of each cell. When cells divide, a chromosome occasionally breaks and the fragment can get stuck onto another chromosome. In addition, fragments may break off from two different chromosomes and swap places.

Chromosomal breakages, also referred to as translocations, are thought to be important in terms of evolution. When chromosomes break in egg or sperm cells, opportunities arise for the rearrangement of DNA in the resulting offspring. Such inheritable rearrangements may be lethal or cause disease. However, in some cases, the breaks may lead to the production of new or altered proteins with potential to benefit an organism. In addition to their evolutionary implications, chromosomal translocations are known to contribute to the development or progression of many types of cancer.

In their paper, researchers report that the chromosomal abnormalities most frequently associated with human cancer are far more likely to occur in or near the evolutionary breakage hotspots than are less common types of cancer-associated abnormalities. Researchers theorize that the rearrangements seen near breakage hotspots may activate genes that trigger cancer and/or inactivate genes that normally suppress cancer. However, they emphasize that far more work remains to be done to clarify the relationship between cancer and the breakage hotspots. One thing researchers have determined is that the regions immediately flanking the breakage hotspots contain more genes, on average, than the rest of the genome.

The team was led by Harris A. Lewin, Ph.D., of the University of Illinois at Urbana-Champaign, and William J. Murphy, Ph.D., of Texas A&M University in College Station. Mapping data for the dog genome were provided by NHGRI's Elaine Ostrander, Ph.D., and Heidi G. Parker, Ph.D., along with scientists from the French National Center for Scientific Research at the University of Rennes. Other study participants were from the National Cancer Institute, the Genome Institute of Singapore and the University of California at San Diego.

"Science tells us that the most effective tool we currently have to understand our own genome is to compare it with the genomes of other organisms. With each new genome that we sequence, we move closer to filling the gaps in our knowledge," said Dr. Ostrander, who is chief of the Cancer Genetics Branch in NHGRI's Division of Intramural Research.

The multi-species comparison published in Science also yielded surprising results about the rate at which chromosomal evolution occurs. Based on an analysis that included a computer-generated reconstruction of the genomes of long-extinct mammals, researchers found the rate of chromosomal evolution among mammals dramatically accelerated following the extinction of the dinosaurs about 65 million years ago.

Before the sudden demise of dinosaurs and many other types of animals, which is thought to have resulted from a massive comet or asteroid striking Earth, mammals shared fairly similar body plans and also fairly similar genomes. Researchers speculate that the mass extinction opened new ecological niches for mammals, spurring their diversification and the emergence of new mammalian orders. This situation would have facilitated opportunities for the isolation of mammals into more distinct breeding groups, speeding the development of species-specific chromosomes.

"This study has revealed many hidden secrets on the nature and timing of genome evolution in mammals, and it demonstrates how the study of basic evolutionary processes can lead to new insights into the origin of human diseases," said Dr. Lewin, who is director of the Institute of Genomic Biology at the University of Illinois.

Long-lived, Quiescent Retroelements are a Major Driving force in Human Genome Evolution

Mon, 02 May 2005 13:30:38 PST

( from http://www.rxpgnews.com ) Louisiana State University scientists in the Department of Biological Sciences have unraveled the details of a 25-million-year-old evolutionary process in the human genome. Specific DNA sequences that appear to have persisted in a latent state for long periods of time may not be simply lying dormant. Instead, the researchers say that these elements have played a crucial role in human evolution by surreptitiously spawning hyperactive progeny copies, giving rise to the most abundant family of DNA elements in the human genome: Alu elements. The study, which was led by LSU scientist Dr. Mark A. Batzer, provides the first strong mechanistic evidence for the evolution of Alu elements to date.

Alu elements are short, 300-nucleotide-long DNA sequences capable of copying themselves, mobilizing through an RNA intermediate, and inserting into another location in the genome. Over evolutionary time, this retrotransposition activity has led to the generation of over one million copies of Alu elements in the human genome, making them the most abundant type of sequence present. Because Alu elements are so abundant, comprising approximately 10% of the total human genome, they have been thoroughly characterized in terms of their origin and sequence composition. What has remained elusive to scientists, however, are the actual mechanisms by which these elements persist and propagate over time to influence human evolution.

In an attempt to understand these mechanisms, Dr. Batzer and his colleagues examined a subfamily of Alu elements in the human genome known as the AluYb lineage, and compared these elements to those in the genomes of other primate species, including chimpanzees, bonobos, gorillas, orangutans, gibbons and siamangs. The AluYb subfamily accounts for approximately 40% of all human-specific Alu elements and is currently one of the most active Alu lineages in the human genome. Some AluYb elements are still actively mobilizing in the human genome, causing insertion mutations that have led to the development of a number of heritable diseases.

Dr. Batzer's team demonstrated that some AluYb subfamily members have orthologs in all primate genomes tested, which dates the AluYb linage to an origin approximately 18-25 million years ago. Their results also indicated that the AluYb subfamily underwent a major species-specific expansion in the human genome during the past 3-4 million years. This apparent 20-million-year stretch of retrotranspositional quiescence, followed by a sudden outburst of human-specific retrotransposition activity in the past few million years, led Dr. Batzer and colleagues to formulate a new theory for the evolution of Alu elements, termed the "stealth driver" model. In the "stealth driver" model, low-activity Alu elements are maintained in low-copy number for long periods of time and occasionally produce short-lived hyperactive progeny that contribute to the formation and expansion of Alu elements in the human genome.

To date, the most widely accepted theory of Alu retrotransposition is called the "master gene" theory, which asserts that the majority of Alu retrotransposition activity is driven by a small number of hyperactive "master" sequences. In this model, mutations occurring in the "master" copies have rendered themselves capable of substantial propagation and persistence over time. However, prior evidence from the Ya5 subfamily indicated that at least some "master" Alu elements may persist in low-copy numbers for long periods of evolutionary time without retrotranspositional activity, suggesting that the mechanisms of Alu expansion may be much more complex. These observations led Dr. Batzer and his co-workers to examine the Yb subfamily of Alu elements, to demonstrate that the Yb subfamily has a similar evolutionary pattern to that of AluYa5, and to formulate the "stealth driver" hypothesis for the evolution of these Alu elements.

"In contrast to 'master' genes, 'stealth drivers' are not responsible for generating the majority of new Alu copies, but rather for maintaining genomic retrotransposition capacity over extended periods of time," Batzer explains. "By generating new Alu copies at a slow rate, a 'stealth driver' may occasionally spawn progeny elements that are capable of much higher retrotransposition rates. These hyperactive progeny elements may act as 'master' genes for the amplification of Alu subfamilies and are responsible for producing the majority of the subfamily members. Due to their high retrotransposition levels, however, they are likely to be rapidly purged from human populations through natural selection."