Biologists Wake Dormant Viruses and Uncover Mechanism for Survival.

This shows the functioning of Kap1 protein in mouse embrocation cells. (Credit: Pascal Coderay, pascal@salut.ch)

Source: ScienceDaily

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ScienceDaily (Jan. 14, 2010) — It is known that viral "squatters" comprise nearly half of our genetic code. These genomic invaders inserted their DNA into our own millions of years ago when they infected our ancestors. But just how we keep them quiet and prevent them from attack was more of a mystery until EPFL researchers revived them.

The reason we survive the presence of these endogenous retroviruses -- viruses that attack and are passed on through germ cells, the cells that give rise to eggs and sperm -- is because something keeps the killers silent. Now, publishing in the journal Nature, Didier Trono and his team from EPFL, in Switzerland, describe the mechanism. Their results provide insights into evolution and suggest potential new therapies in fighting another retrovirus -- HIV.
By analysing embryonic stem cells in mice within the first few days of life, Trono and team discovered that mouse DNA codes for an army of auxiliary proteins that recognize the numerous viral sequences littering the genome. The researchers also demonstrated that a master regulatory protein called KAP1 appears to orchestrate these inhibitory proteins in silencing would-be viruses. When KAP1 is removed, for example, the viral DNA "wakes up," multiplies, induces innumerable mutations, and the embryo soon dies.
Because retroviruses tend to mutate their host's DNA, they have an immense power and potential to alter genes. And during ancient pandemics, some individuals managed to silence the retrovirus involved and therefore survived to pass on the ability. Trono explains that the great waves of endogenous retrovirus appearance coincide with times when evolution seemed to leap ahead.
"In our genome we find traces of the last two major waves. The first took place 100 million years ago, at the time when mammals started to develop, and the second about fifty million years ago, just before the first anthropoid primates," he says.
The discovery of the KAP1 mechanism could be of interest in the search for new therapeutic approaches to combat AIDS. The virus that causes AIDS can lie dormant in the red blood cells it infects, keeping it hidden from potential treatments. Waking the virus up could expose it to attack.
Co-authors include Helen M. Rowe, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland; Johan Jakobsson, EPFL and Wallenberg Neuroscience Center, Department of Experimental Medical Sciences, Lund University, Sweden; Daniel Mesnard, EPFL; Jacques Rougemont, EPFL; Séverine Reynard, EPFL; Tugce Aktas, EMBL Heidelberg, Germany; Pierre V. Maillard, EPFL; Hillary Layard-Liesching, EPFL; Sonia Verp, EPFL; Julien Marquis, EPFL; François Spitz, EMBL Heidelberg, Germany; Daniel B. Constam, EPFL; and Didier Trono, EPFL.

Story Source:
Adapted from materials provided by Ecole Polytechnique Fédérale de Lausanne, via EurekAlert!, a service of AAAS.

Chimp and human Y chromosomes evolving faster than expected.

Source: Physorg.com

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Contrary to a widely held scientific theory that the mammalian Y chromosome is slowly decaying or stagnating, new evidence suggests that in fact the Y is actually evolving quite rapidly through continuous, wholesale renovation.

By conducting the first comprehensive interspecies comparison of Y chromosomes, Whitehead Institute researchers have found considerable differences in the genetic sequences of the human and chimpanzee Ys—an indication that these chromosomes have evolved more quickly than the rest of their respective genomes over the 6 million years since they emerged from a common ancestor. The findings are published online this week in the journal Nature.
"The region of the Y that is evolving the fastest is the part that plays a role in sperm production," say Jennifer Hughes, first author on the Nature paper and a postdoctoral researcher in Whitehead Institute Director David Page's lab. "The rest of the Y is evolving more like the rest of the genome, only a little bit faster."
The chimp Y chromosome is only the second Y chromosome to be comprehensively sequenced. The original chimp genome sequencing completed in 2005 largely excluded the Y chromosome because its hundreds of repetitive sections typically confound standard sequencing techniques. Working closely with the Genome Center at Washington University, the Page lab managed to painstakingly sequence the chimp Y chromosome, allowing for comparison with the human Y, which the Page lab and the Genome Center at Washington University had sequenced successfully back in 2003.
The results overturned the expectation that the chimp and human Y chromosomes would be highly similar. Instead, they differ remarkably in their structure and gene content. The chimp Y, for example, has lost one third to one half of the human Y chromosome genes--a significant change in a relatively short period of time. Page points out that this is not all about gene decay or loss. He likens the Y chromosome changes to a home undergoing continual renovation.
"People are living in the house, but there's always some room that's being demolished and reconstructed," says Page, who is also a Howard Hughes Medical Institute investigator. "And this is not the norm for the genome as a whole."

Wes Warren, Assistant Director of the Washington University Genome Center, agrees. "This work clearly shows that the Y is pretty ingenious at using different tools than the rest of the genome to maintain diversity of genes," he says. "These findings demonstrate that our knowledge of the Y chromosome is still advancing."
Hughes and Page theorize that the divergent evolution of the chimp and human Y chromosomes may be due to several factors, including traits specific to Y chromosomes and differences in mating behaviors.
Because multiple male chimpanzees may mate with a single female in rapid succession, the males' sperm wind up in heated reproductive competition. If a given male produces more sperm, that male would theoretically be more likely to impregnate the female, thereby passing on his superior sperm production genes, some of which may be residing on the Y chromosome, to the next generation.
Because selective pressure to pass on advantageous sperm production genes is so high, those genes may also drag along detrimental genetic traits to the next generation. Such transmission is allowed to occur because, unlike other chromosomes, the Y has no partner with which to swap genes during cell division. Swapping genes between chromosomal partners can eventually associate positive gene versions with each other and eliminate detrimental gene versions. Without this ability, the Y chromosome is treated by evolution as one large entity. Either the entire chromosome is advantageous, or it is not.
In chimps, this potent combination of intense selective pressure on sperm production genes and the inability to swap genes may have fueled the Y chromosome's rapid evolution. Disadvantages from a less-than-ideal gene version or even the deletion of a section of the chromosome may have been outweighed by the advantage of improved sperm production, resulting in a Y chromosome with far fewer genes than its human counterpart.
To determine whether this rapid rate of evolution affects Y chromosomes beyond those of chimps and humans, the Page lab and the Washington University Genome Center are now sequencing and examining the Y chromosomes of several other mammals.
Provided by Massachusetts Institute of Technology.

Scientists sequence soybean genome, reveal pathways for improving biodiesel.

Soybean, one of the most important global sources of protein and oil, is now the first legume species with a published complete draft genome sequence. Credit: Roy Kaltschmidt, Lawrence Berkeley National Laboratory.

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Source: Physorg.com

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Soybean, one of the most important global sources of protein and oil, is now the first legume species with a published complete draft genome sequence. The sequence and its analysis appear in the January 14 edition of the journal Nature.

The research team comprised 18 institutions, including the U.S. Department of Energy Joint Genome Institute (DOE JGI), the U.S. Department of Agriculture-Agricultural Research Service (USDA-ARS), Purdue University and the University of North Carolina at Charlotte. The DOE, National Science Foundation, USDA and United Soybean Board supported the research.
"The soybean genome's billion-plus nucleotides afford us a better understanding of the plant's capacity to turn sunlight, carbon dioxide, nitrogen and water, into concentrated energy, protein, and nutrients for human and animal use," said Anna Palmisano, DOE Associate Director of Science for Biological and Environmental Research. "This opens the door to crop improvements that are sorely needed for energy production, sustainable human and animal food production, and a healthy environmental balance in agriculture worldwide."
With the soybean genetic code now determined, the research community has access to a key reference for more than 20,000 legume species and can explore the extraordinary evolutionary innovation of nitrogen-fixing symbiosis that is so critically important to successful agricultural crop rotation strategies.
Jeremy Schmutz, the study's first author and a DOE JGI scientist at the HudsonAlpha Institute for Biotechnology in Alabama, said that the soybean sequencing was the largest plant project done to date at the DOE Joint Genome Institute. "It also happens to be the largest plant that's ever been sequenced by the whole genome shotgun strategy—where we break it apart and reassemble it like a huge puzzle," he said. Of the more than 20 other plant genomes taken on by the DOE JGI, those already sequenced include the black cottonwood (poplar) tree and the grain sorghum, both targeted because of their promise as biomass feedstocks for biofuels production.
"This is a milestone for soybean research and promises to usher in a new era in soybean agronomic improvement," said co-author Gary Stacey, Director, Center for Sustainable Energy and Associate Director and National Center for Soybean Biotechnology, University of Missouri. "The genome provides a parts list of what it takes to make a soybean plant and, more importantly, helps to identify those genes that are essential for such important agronomic traits as protein and oil content."

From the sequence analysis, Stacey said that he and his colleagues have identified more than 46,000 genes of which 1,110 are involved in lipid metabolism. "These genes and their associated pathways are the building blocks for soybean oil content and represent targets that can be modified to bolster output and lead to the increase of the use of soybean oil for biodiesel production."
While biodiesel from soybean oil represents a cleaner, renewable alternative to fossil fuels with desirable properties as a liquid transportation fuel, there simply is not enough oil produced by the plant to be a competitive gasoline on a gallons-of-fuel yield per acre. The availability of the soybean genome may provide some key solutions. "We can now zero in on the control points governing carbon flow towards protein and oil," said Tom Clemente, Professor, Center for Biotechnology, Center for Plant Science Innovation at the University of Nebraska, Lincoln. "With the combination of informatics, biochemistry and genetics we can target the development of a soybean with greater than 40 percent oil content."
The availability of the soybean genome sequence has accelerated other soybean trait discovery efforts as well. For example, researchers have used the sequence to zero in on a mutation that can be used to select for a line that has lower levels of the sugar stachyose, which will improve the ability of animals and humans to digest soybeans.

In another effort, by comparing the genomes of soybean and corn, a single-base pair mutation was found that causes a reduction in phytate production in soybean. Phytate is the form in which phosphorous is stored in plant tissue. Because phytate is not absorbed by the animals that eat the feed, the unabsorbed phytate passes through the gastrointestinal tract, elevating the amount of phosphorus in the manure. Limiting phytate production in the soybean could reduce a major environmental runoff contaminant from swine and poultry waste.
Of additional importance for soybean farmers is that the genome sequence has provided access to the first resistance gene for the devastating disease Asian Soybean Rust (ASR). In countries where ASR is well established, soybean yield losses due to the disease can be as high as 80 percent.

Provided by DOE/Joint Genome Institute

Chimp and Human Y Chromosomes Evolving Faster Than Expected.

Contrary to a widely held scientific theory that the mammalian Y chromosome is slowly decaying or stagnating, new evidence suggests that in fact the Y is actually evolving quite rapidly through continuous, wholesale renovation. (Credit: iStockphoto/Wesley Jenkins)

Source: ScienceDaily

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ScienceDaily (Jan. 13, 2010) — Contrary to a widely held scientific theory that the mammalian Y chromosome is slowly decaying or stagnating, new evidence suggests that in fact the Y is actually evolving quite rapidly through continuous, wholesale renovation.

By conducting the first comprehensive interspecies comparison of Y chromosomes, Whitehead Institute researchers have found considerable differences in the genetic sequences of the human and chimpanzee Ys -- an indication that these chromosomes have evolved more quickly than the rest of their respective genomes over the 6 million years since they emerged from a common ancestor. The findings are published online this week in the journal Nature.
"The region of the Y that is evolving the fastest is the part that plays a role in sperm production," say Jennifer Hughes, first author on the Nature paper and a postdoctoral researcher in Whitehead Institute Director David Page's lab. "The rest of the Y is evolving more like the rest of the genome, only a little bit faster."
The chimp Y chromosome is only the second Y chromosome to be comprehensively sequenced. The original chimp genome sequencing completed in 2005 largely excluded the Y chromosome because its hundreds of repetitive sections typically confound standard sequencing techniques. Working closely with the Genome Center at Washington University, the Page lab managed to painstakingly sequence the chimp Y chromosome, allowing for comparison with the human Y, which the Page lab and the Genome Center at Washington University had sequenced successfully back in 2003.
The results overturned the expectation that the chimp and human Y chromosomes would be highly similar. Instead, they differ remarkably in their structure and gene content. The chimp Y, for example, has lost one third to one half of the human Y chromosome genes--a significant change in a relatively short period of time. Page points out that this is not all about gene decay or loss. He likens the Y chromosome changes to a home undergoing continual renovation.
"People are living in the house, but there's always some room that's being demolished and reconstructed," says Page, who is also a Howard Hughes Medical Institute investigator. "And this is not the norm for the genome as a whole."
Wes Warren, Assistant Director of the Washington University Genome Center, agrees. "This work clearly shows that the Y is pretty ingenious at using different tools than the rest of the genome to maintain diversity of genes," he says. "These findings demonstrate that our knowledge of the Y chromosome is still advancing."
Hughes and Page theorize that the divergent evolution of the chimp and human Y chromosomes may be due to several factors, including traits specific to Y chromosomes and differences in mating behaviors.
Because multiple male chimpanzees may mate with a single female in rapid succession, the males' sperm wind up in heated reproductive competition. If a given male produces more sperm, that male would theoretically be more likely to impregnate the female, thereby passing on his superior sperm production genes, some of which may be residing on the Y chromosome, to the next generation.
Because selective pressure to pass on advantageous sperm production genes is so high, those genes may also drag along detrimental genetic traits to the next generation. Such transmission is allowed to occur because, unlike other chromosomes, the Y has no partner with which to swap genes during cell division. Swapping genes between chromosomal partners can eventually associate positive gene versions with each other and eliminate detrimental gene versions. Without this ability, the Y chromosome is treated by evolution as one large entity. Either the entire chromosome is advantageous, or it is not.
In chimps, this potent combination of intense selective pressure on sperm production genes and the inability to swap genes may have fueled the Y chromosome's rapid evolution. Disadvantages from a less-than-ideal gene version or even the deletion of a section of the chromosome may have been outweighed by the advantage of improved sperm production, resulting in a Y chromosome with far fewer genes than its human counterpart.
To determine whether this rapid rate of evolution affects Y chromosomes beyond those of chimps and humans, the Page lab and the Washington University Genome Center are now sequencing and examining the Y chromosomes of several other mammals.
This research was funded by the National Institutes of Health (NIH) and the Howard Hughes Medical Institute (HHMI).

Story Source:
Adapted from materials provided by Whitehead Institute for Biomedical Research. Original article written by Nicole Giese.
Journal Reference:
1. Jennifer F. Hughes, Helen Skaletsky, Tatyana Pyntikova, Tina A. Graves, Saskia K. M. Van Daalen, Patrick J. Minx, Robert S. Fulton, Sean D. Mcgrath, Devin P. Locke, Cynthia Friedman, Barbara J. Trask, Elaine R. Mardis, Wesley C. Warren, Sjoerd Repping, Steve Rozen, Richard K. Wilson, David C. Page. Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content. Nature, Online January 13, 2010

'Longevity Gene' Helps Prevent Memory Decline and Dementia.

Scientists at Albert Einstein College of Medicine of Yeshiva University have found that a "longevity gene" helps to slow age-related decline in brain function in older adults. Drugs that mimic the gene's effect are now under development, the researchers note, and could help protect against Alzheimer's disease. (Credit: iStockphoto/Anne De Haas)

Source: ScienceDaily

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ScienceDaily (Jan. 13, 2010) — Scientists at Albert Einstein College of Medicine of Yeshiva University have found that a "longevity gene" helps to slow age-related decline in brain function in older adults. Drugs that mimic the gene's effect are now under development, the researchers note, and could help protect against Alzheimer's disease.

The paper describing the Einstein study is published in the January 13 edition of the Journal of the American Medical Association.
"Most work on the genetics of Alzheimer's disease has focused on factors that increase the danger," said Richard B. Lipton, M.D., the Lotti and Bernard Benson Faculty Scholar in Alzheimer's Disease and professor and vice chair in the Saul R. Korey Department of Neurology at Einstein and senior author of the paper. As an example, he cites APOE ε4, a gene variant involved in cholesterol metabolism that is known to increase the risk of Alzheimer's among those who carry it.
"We reversed this approach," says Dr. Lipton, "and instead focused on a genetic factor that protects against age-related illnesses, including both memory decline and Alzheimer's disease."
In a 2003 study, Dr. Lipton and his colleagues identified the cholesteryl ester transfer protein (CETP) gene variant as a "longevity gene" in a population of Ashkenazi Jews. The favorable CETP gene variant increases blood levels of high-density lipoprotein (HDL) -- the so-called good cholesterol -- and also results in larger-than-average HDL and low-density lipoprotein (LDL) particles.
The researchers of the current study hypothesized that the CETP longevity gene might also be associated with less cognitive decline as people grow older. To find out, they examined data from 523 participants from the Einstein Aging Study, an ongoing federally funded project that has followed a racially and ethnically diverse population of elderly Bronx residents for 25 years.
At the beginning of the study, the 523 participants -- all of them 70 or over -- were cognitively healthy, and their blood samples were analyzed to determine which CETP gene variant they carried. They were then followed for an average of four years and tested annually to assess their rates of cognitive decline, the incidence of Alzheimer's disease and other changes.
"We found that people with two copies of the longevity variant of CETP had slower memory decline and a lower risk for developing dementia and Alzheimer's disease," says Amy E. Sanders, M.D., assistant professor in the Saul R. Korey Department of Neurology at Einstein and lead author of the paper. "More specifically, those participants who carried two copies of the favorable CETP variant had a 70 percent reduction in their risk for developing Alzheimer's disease compared with participants who carried no copies of this gene variant."
The favorable gene variant alters CETP so that the protein functions less well than usual. Dr. Lipton notes that drugs are now being developed that duplicate this effect on the CETP protein. "These agents should be tested for their ability to promote successful aging and prevent Alzheimer's disease," he recommends.
The research was funded by the National Institute on Aging, one of the 27 institutes and centers of the National Institutes of Health.

Story Source:
Adapted from materials provided by Albert Einstein College of Medicine.

Journal Reference:
1. Sanders et al. Association of a Functional Polymorphism in the Cholesteryl Ester Transfer Protein (CETP) Gene With Memory Decline and Incidence of Dementia. JAMA The Journal of the American Medical Association, 2010; 303 (2): 150 DOI: 10.1001/jama.2009.1988

Scientists discover new protein function.

Source: Physorg.com

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Carnegie Mellon University's Philip R. LeDuc and his collaborators in Massachusetts and Taiwan have discovered a new function of a protein that could ultimately unlock the mystery of how these workhorses of the body play a central role in the mechanics of biological processes in people.

"What we have done is find a new function of a protein that helps control cell behavior from a mechanics perspective," said LeDuc, an associate professor of mechanical engineering with courtesy appointments in the Biomedical Engineering, Biological Sciences and Computational Biology departments.
"For over 15 years, researchers have been mainly focusing on a protein called Integrin to study these cell functions, but our team found that another lesser known protein called Syndecan-4 is extremely important in cell behavior in a field called MechanoBiology (a field linking mechanics and biology). Syndecan-4 is known to play an essential role in a variety of diseases like cancer," LeDuc said.
LeDuc's new findings appear in the Dec. 29 edition of the prestigious journal Proceedings of the National Academy of Sciences along with complementary work that is appearing in another highly respected journal, Nature Protocols.
Essentially what his research does is take a look at how a protein's shape and form determines how it functions in the human body from a mechanics perspective. Proteins are composed of long chains of amino acids than can form bonds with other molecules in a chain, kinking, twisting and folding into complicated, three-dimensional shapes, such as helices or densely furrowed globular structures.
"These folded shapes are immensely important because they can define a protein's function in the cell," said LeDuc, who is also developing novel biologically inspired diagnostic approaches and materials as well as computational methods to understand molecular behavior.
LeDuc said his research finds that some protein shapes fit perfectly into cell receptors, turning chemical processes on and off, like a key in a lock. With mechanics changing the shape of proteins, LeDuc says the key might no longer fit into the lock, and serious consequences in the body can occur when proteins fail to assume their preordained shapes or fail to connect properly.
"Misguided proteins have been linked to disease such as cancer, arthritis and wound healing, among others," LeDuc said. "Our research is looking at how protein shapes affect cells and how cell biomechanics impacts the entire process."
Provided by Carnegie Mellon University

Genome of Woodland Strawberry, a Model System for Rosaceae Plants, Sequenced.

Source: ScienceDaily

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ScienceDaily (Jan. 12, 2010) — The genome of a model plant related to peach, cherry and cultivated strawberry has been sequenced by a consortium of international researchers that includes scientists with the Agricultural Research Service (ARS).

Fragaria vesca, commonly known as the woodland or alpine strawberry, is a member of the Rosaceae family, which consists of more than 100 genera and 3,000 species. This large family includes many economically important and popular fruit, nut, ornamental and woody crops, such as almond, apple, peach, cherry, raspberry, strawberry and rose.
F. vesca has many traits that make it an attractive model system for functional genomics studies. Its small size and rapid life cycle enable researchers to conduct genetic analyses with great efficiency and low cost. To determine the importance of a gene of interest, F. vesca can be transformed in order to modulate the activity of that gene in the plant. Most importantly, F. vesca has a relatively small genome, yet shares most gene sequences with other members of the Rosaceae family, making it an important tool for addressing questions regarding gene function.
ARS molecular biologist Janet Slovin, with the Genetic Improvement of Fruits and Vegetables Laboratory in Beltsville, Md., created the nearly inbred line used in the F. vesca genome sequencing project. Named "Hawaii 4," this line allowed the researchers to more easily program a computer to piece the genome together from the relatively short lengths of sequence data generated by modern sequencing machines.
Although the F. vesca genome is a model genome for the Rosaceae group, critical regulatory gene functions will probably differ, hypothesizes Slovin. Scientists can use the genome sequence to identify these genes, to test their function in F. vesca, and to develop molecular genetic markers for more rapid breeding of crops belonging to the Rosaceae group. Slovin will use the genome to study and improve heat tolerance during fruit production in strawberry.
The scientists announced the sequencing of the genome of woodland strawberry January 9 at the Plant and Animal Genome Conference in San Diego, Ca. The project was funded by Roche Diagnostics.

Story Source:
Adapted from materials provided by United States Department of Agriculture-Research, Education, and Economics.

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Evolutionary Surprise: Eight Percent of Human Genetic Material Comes from a Virus.

Source: ScienceDaily

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ScienceDaily (Jan. 8, 2010) — About eight percent of human genetic material comes from a virus and not from our ancestors, according to researchers in Japan and the U.S.

The study, and an accompanying News & Views article by University of Texas at Arlington biology professor Cédric Feschotte, is published in the journal Nature.
The research showed that the genomes of humans and other mammals contain DNA derived from the insertion of bornaviruses, RNA viruses whose replication and transcription takes place in the nucleus. Feschotte wrote on recent research led by Professor Keizo Tomonaga at Osaka University in Japan. Feschotte said this virally transmitted DNA may be a cause of mutation and psychiatric disorders such as schizophrenia and mood disorders.
In his article, Feschotte speculates about the role of such viral insertions in causing mutations with evolutionary and medical consequences.
The assimilation of viral sequences into the host genome is a process referred to as endogenization. This occurs when viral DNA integrates into a chromosome of reproductive cells and is subsequently passed from parent to offspring. Until now, retroviruses were the only viruses known to generate such endogenous copies in vertebrates. But Feschotte said that scientists have found that non-retroviral viruses called bornaviruses have been endogenized repeatedly in mammals throughout evolution.
Bornavirus (BDV) owes its name to the town of Borna, Germany, where a virus epidemic in 1885 wiped out a regiment of cavalry horses. BDV infects a range of birds and mammals, including humans. It is unique because it infects only neurons, establishing a persistent infection in its host's brain, and its entire life cycle takes place in the nucleus of the infected cells. Feschotte said this intimate association of BDV with the cell nucleus prompted researchers to investigate whether bornaviruses may have left behind a record of past infection in the form of endogenous elements. They searched the 234 known eukaryotic genomes (those genomes that have been fully sequenced) for sequences that are similar to that of BDV. "The researchers unearthed a plethora of endogenous Borna-like N (EBLN) elements in many diverse mammals, " Feschotte said.
The scientists also were able to recover spontaneous BDV insertions in the chromosomes of human cultured cells persistently infected by BVD.Based on these data, Feschotte proposes that BDV insertions could be a source of mutations in the brain cells of infected individuals.
"These data yield a testable hypothesis for the alleged, but still controversial, causative association of BDV infection with schizophrenia and mood disorders," Feschotte said. The research in Feschotte 's laboratory, which largely focuses on transposable elements, the genetic elements that are able to move and replicate within the genomes of virtually all living organisms, is representative of the research under way at UT Arlington, an institution of 28,000 students on its way to becoming a nationally recognized, top-tier research university.

Story Source:
Adapted from materials provided by University of Texas at Arlington.

Journal References:
1.Masayuki Horie, Tomoyuki Honda, Yoshiyuki Suzuki, Yuki Kobayashi, Takuji Daito, Tatsuo Oshida, Kazuyoshi Ikuta, Patric Jern, Takashi Gojobori, John M. Coffin & Keizo Tomonaga. Endogenous non-retroviral RNA virus elements in mammalian genomes. Nature, 2010; 463 (7277): 84 DOI: 10.1038/nature08695
2.Cédric Feschotte. Virology: Bornavirus enters the genome. Nature, 2010; 463 (7277): 39 DOI: 10.1038/463039a

Evolution's Footprints in Human Genome Precisely Tracked Using New Approach.

Source: ScienceDaily

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ScienceDaily (Jan. 8, 2010) — Fossils may provide tantalizing clues to human history but they also lack some vital information, such as revealing which pieces of human DNA have been favored by evolution because they confer beneficial traits -- resistance to infection or the ability to digest milk, for example. These signs can only be revealed through genetic studies of modern humans and other related species, though the task has proven difficult.

Now, in a paper appearing in the January 7 edition of Science Express, researchers describe a method for pinpointing these preferred regions within the human genome that offers greater precision and resolution than ever before, and the possibility of deeply understanding both our genetic past and present.
"It's clear that positive natural selection has been a critical force in shaping the human genome, but there are remarkably few examples that have been clearly identified," said senior author Pardis Sabeti, an associate member of the Broad Institute of Harvard and MIT and an assistant professor of organismic and evolutionary biology at Harvard University. "The method we've developed makes it possible to zero in on individual genes as well as the specific changes within them that are driving important evolutionary changes."
Positive natural selection is a process in which advantageous traits become more common in a population. That is because these traits boost an individual's chances of survival and reproduction, so they are readily passed on to future generations. Identifying such traits -- and the genes underlying them -- is a cornerstone of current efforts to dissect the biological history of the human species as well as the diseases that threaten human health today.
"In the human genome, positive natural selection leaves behind very distinctive signals," said co-first author Sharon Grossman, a research assistant at Harvard University and the Broad Institute. Yet earlier methods for detecting these signals are limited, highlighting relatively large chunks of the genome that are hundreds of thousands to millions of genetic letters or "bases" in length, and that can contain many genes.
Of the hundreds of these large genomic regions thought to be under positive natural selection in humans, only a handful have so far been winnowed to a precise genetic change. "Finding the specific genetic changes that are under selection can be like looking for a needle in a haystack," said Grossman.
Sabeti, Grossman and their colleagues wondered if there might be a way to enhance this genomic search. Because existing methods for detecting natural selection each measure distinct genomic features, the researchers predicted that an approach that combines them together could yield even better results.
After some initial simulations to test their new method, the research team applied it to more than 180 regions of the human genome that are thought to be under recent positive selection, yet in most cases, the specific gene or genetic variant under selection is unknown.
The researchers' method, called "Composite of Multiple Signals" or CMS, enabled them to dramatically narrow the size of the candidate regions, reducing them from an average of eight genes per region to one. Moreover the number of candidate genetic changes was reduced from thousands to just a handful, helping the researchers tease out the needles from the haystack.
"The list of genes and genetic loci we identified includes many intriguing candidates to follow up," said co-first author Ilya Shylakhter, a computational biologist at the Broad Institute and Harvard University. "For example, a number of genes identified are involved in metabolism, skin pigmentation and the immune system."
In some cases, the researchers were able to identify a specific genetic change that is the likely focal point of natural selection. For example, a variation in a gene called protocadherin 15, which functions in sensory perception, including hearing and vision, appears to be under selection in some East Asian populations. Several other genes involved in sensory perception also appear to be under selection in Asia. In addition, the team uncovered strong evidence of selection in East Asians at a specific point within the leptin receptor gene, which is linked to blood pressure, body mass index and other important metabolic functions.
Interestingly, the researchers also localized signals to regions outside of genes, suggesting that they function not by altering gene structure per se, but by changing how certain genes are turned on and off.
While the findings in the Science paper offer a deep glimpse of evolution's handiwork, the researchers emphasize that further studies of individual genetic variations, involving experiments that explore how certain genetic changes influence biological function, are necessary to fully dissect the role of natural selection and its impact on human biology.
"This method allows us to trace evolution's footprints with a much finer level of granularity than before, but it's one piece of a much larger puzzle," said Sabeti. "As more data on human genetic variation becomes available in the coming years, an even more detailed evolutionary picture should emerge."

Story Source:
Adapted from materials provided by Broad Institute of MIT and Harvard, via EurekAlert!, a service of AAAS.

Journal Reference:
Grossman et al. A composite of multiple signals distinguishes causal variants in regions of positive selection. Science, 2010 DOI: 10.1126/science.1183863

What Came First in the Origin of Life? New Study Contradicts the 'Metabolism First' Hypothesis.

Source: ScienceDaily

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ScienceDaily (Jan. 9, 2010) — A new study published in Proceedings of National Academy of Sciences rejects the theory that the origin of life stems from a system of self-catalytic molecules capable of experiencing Darwinian evolution without the need of RNA or DNA and their replication.

The research, which was carried out with the participation of Mauro Santos, researcher of the Department of Genetics and Microbiology at Universitat Autònoma de Barcelona (UAB), has demonstrated that, through the analysis of what some researchers name "compound genomes," these chemical networks cannot be considered evolutionary units because they lose properties which are essential for evolution when they reach a critical size and greater level of complexity.
The U.S. National Aeronautics and Space Administration (NASA) defines life as a "self-sustaining chemical system capable of Darwinian evolution." The scientific theories on the origin of life revolve around two main ideas: one focuses on genetics -- with RNA or DNA replication as an essential condition for Darwinian evolution to take place -- and the other focuses on metabolism. It is clear that both situations must have begun with simple organic molecules formed by prebiotic processes, as was demonstrated by the Miller-Urey experiment (in which organic molecules were created from inorganic substances). The point in which these two theories differ is that the replication of RNA or DNA molecules is a far too complex process which requires a correct combination of monomers within the polymers to produce a molecular chain resulting from the replication.
Until now no plausible chemical explanation exists for how these processes occured. In addition, defenders of the second theory argue that the processes needed for evolution to take place depend on primordial metabolism. This metabolism is believed to be a type of chemical network entailing a high degree of mutual catalysis between its components which, in turn, eventually allows for adaptation and evolution without any molecular replication.
In the first half of the 20th century, Alexander Oparin established the "Metabolism First" hypothesis to explain the origin of life, thus strengthening the primary role of cells as small drops of coacervates (evolutionary precursors of the first prokaryote cells). Dr Oparin did not refer to RNA or DNA molecules since at that time it was not clear just how important the role of these molecules was in living organisms. However he did form a solid base for the idea of self-replication as a collective property of molecular compounds.
Science more recently demonstrated that sets of chemical components store information about their composition which can be duplicated and transmitted to their descendents. This has led to their being named "compound genomes" or composomes. In other words, heredity does not require information in order to be stored in RNA or DNA molecules. These "compound genomes" apparently fulfil the conditions required to be considered evolutionary units, which suggests a pathway from pre-Darwinian dynamics to a minimum protocell.
Researchers in this study nevertheless reveal that these systems are incapable of undergoing a Darwinian evolution. For the first time a rigorous analysis was carried out to study the supposed evolution of these molecular networks using a combination of numerical and analytical simulations and network analysis approximations. Their research demonstrated that the dynamics of molecular compound populations which divide after having reached a critical size do not evolve, since during this process the compounds lose properties which are essential for Darwinian evolution.
Researchers concluded that this fundamental limitation of "compound genomes" should lead to caution towards theories that set metabolism first as the origin as life, even though former metabolic systems could have offered a stable habitat in which primitive polymers such as RNA could have evolved.
Researchers state that different prebiotic Earth scenarios can be considered. However, the basic property of life as a system capable of undergoing Darwinian evolution began when genetic information was finally stored and transmitted such as occurs in nucleotide polymers (RNA and DNA).

Story Source:
Adapted from materials provided by Universitat Autonoma de Barcelona.

Journal Reference:
Vera Vasasa, Eörs Szathmáry and Mauro Santosa. Lack of evolvability in self-sustaining autocatalytic networks: A constraint on the metabolism-first path to the origin of life. PNAS, January 4, 2010 DOI: 10.1073/pnas.0912628107