Rat Made Supersmart — Similar Boost Unsafe in Humans?

Matt Kaplan
for National Geographic News

November 12, 2009

By modifying a single gene, scientists have made Hobbie-J the smartest rat in the world, a new study says.

A similar gene tweak might boost human brainpower too, but scientists warn that there is such a thing as being too smart for your own good.

For years scientifically smartened rats have skittered through movies and books such as Flowers for Algernon and The Secret of NIMH. But Hobbie-J is anything but fiction.

The lab rat can remember objects three times longer than her smartest kin, the study says. Thanks largely to this memory boost, she’s also much better at solving complex tasks, such as traveling through mazes using only partial clues to find rewards—a key method for measuring rat intelligence.

Intelligent Redesign

When Hobbie-J was still an embryo, a team led by Joe Z. Tsien at the Medical College of Georgia injected her with genetic material that caused the overexpression of the gene NR2B, which helps control the rate at which brain cells communicate.

The change allowed Hobbie’s brain cells to communicate for a whisker of a second longer than those of normal rats. This, the researchers believe, is why she’s much smarter than the average rat.

(Related: “Blue Rats Move Again After Food-Dye Injection.”)

Dangerous Minds?

Years earlier Tsien and colleagues had given a similar brain boost to a mouse named Doogie, after TV whiz kid Doogie Howser, M.D.

Like the rats of NIMH—”NIMH” being shorthand for the U.S. National Institute of Mental Health—Hobbie-J and Doogie were given intelligence in hopes that the experiments would lead to cures for human brain disorders.

(Related: animal-intelligence pictures.)

“NR2B functioned as a switch to improve learning and memory skills in Doogie, and it is showing the same results in Hobbie-J,” Tsien said via email.

“This suggests that using drugs to target this gene may help to resolve disorders like dementia and Alzheimer’s disease,” he added.

Neuroscientist Guosong Liu, who worked on the Doogie project, said: “The research is all very exciting, because it raises the possibility for us to potentially enhance memory in humans, and that is exactly where my lab is going.”

But there are two major challenges ahead, said Liu, of Tsinghua University in Beijing and the University of Texas, who was not involved in the new study.

First, because genetically modifying human embryos is not considered ethical, doctors would have to find a way to amplify NR2B expression using drugs instead, he said.

Second, mega-memory could be a major burden, even a nightmare, Liu said.

“There is a reason we forget,” he said. “We are supposed to leave our bad experiences behind, so they do not haunt us.”

For this reason, if a drug does become available for human use, Liu said he would only advocate its use in people suffering from significant mental problems such as Alzheimer’s disease.

“The danger of extending memory in healthy people could be considerable” Liu said.

Findings published October 19 in the online journal PLoS ONE.

http://news.nationalgeographic.com/news/2009/11/091112-smartest-rat-memory.html

Barcoding the Planet’s Plant Species

Hundreds of experts from 50 nations are set to agree on a “DNA barcode” system stored on a global database that will be available to scientists around the world that gives every plant on Earth a unique genetic fingerprint.

“Biodiversity scientists are using DNA technology to unravel mysteries, much like detectives use it to solve crimes,” said David Schindel, executive secretary for the Consortium for the Barcode of Life.

“Barcoding is a tool to identify species faster, more cheaply and more precisely than traditional methods, ” explained Patricia Escalante, head of the zoology department at Mexico’s National University (UNAM), which is hosting the gathering. Mexican researchers are also involved in a network to produce barcodes in key taxonomic groups, such as trees, fungi, bees and aquatic insects.

In an effort to limit the impact on the planet’s biodiversity, Dr Escalante said it was vital to establish a reliable monitoring system. “We need an accurate inventory,” she observed, “to recognize parasites of medical, economic or ecological importance. The technology will be used in a number of ways, including identifying the illegal trade in endangered species.

The agreement will be signed at the third International Barcode of Life conference in Mexico City on Tuesday.

http://www.dailygalaxy.com/my_weblog/2009/11/barcoding-the-planets-plant-species.html

Organ Regeneration In Zebrafish: Unraveling The Mechanisms

Unlike humans, zebrafish are able to regenerate amputated appendages. (Credit: Courtesy of the Salk Institute)

The search for the holy grail of regenerative medicine — the ability to “grow back” a perfect body part when one is lost to injury or disease — has been under way for years, yet the steps involved in this seemingly magic process are still poorly understood.

Now researchers at the Salk Institute for Biological Studies have identified an essential cellular pathway in zebrafish that paves the way for limb regeneration by unlocking gene expression patterns last seen during embryonic development. They found that a process known as histone demethylation switches cells at the amputation site from an inactive to an active state, which turns on the genes required to build a copy of the lost limb.

“This is the first real molecular insight into what is happening during limb regeneration,” says first author Scott Stewart, Ph.D., a postdoctoral researcher in the lab of Juan Carlos Izpisúa Belmonte, Ph.D., who led the Salk team. “Until now, how amputation is translated into gene activation has been like magic. Finally we have a handle on a process we can actually follow.”

Their findings, which will be published in a forthcoming issue of Proceedings of the National Academy of Sciences, U.S.A., help to explain how epimorphic regeneration — the regrowing of morphologically and functionally perfect copies of amputated limbs — is controlled, an important step toward understanding why certain animals can do it and we cannot.

“Our experiments show that normal development and limb regeneration are controlled by similar mechanisms,” explains Izpisúa Belmonte, a professor in the Gene Expression Laboratory. “This finding will help us to ask more specific questions about mammalian limb regeneration: Are the same genes involved when we amputate a mammalian limb? If not, what would happen if we turned them on? And if we can affect these methylation marks in an amputated limb, what effect would that have?”

The Belmonte lab uses zebrafish, a small fish from the minnow family, to study limb regeneration. “If you amputate the tail of the zebrafish, it regenerates in about a week, seemingly with no effort and leaving no scar,” explains Stewart. “What’s more, it regenerates a perfect copy and — like growing grass — it will do this over and over again.”

Since regeneration recapitulates in broad strokes embryonic development, during which a complex multi-cellular organism develops from a handful of embryonic stem cells, the researchers began by comparing gene expression patterns between the two processes. During development, genes within specific cell types are turned on and off to trigger the necessary expression patterns that create a whole animal. Once their job is done, they lie silently till they are turned on once again following amputation.

Based on these similarities, Stewart reasoned that genes involved in regeneration may share silencing mechanisms with the ones active in embryonic stem cells. Embryonic stem cells are maintained in a ready-to-go state, “poised” for action to become whatever cell type is needed. The key to this “poised” state are histones, DNA packaging proteins that are also used as carriers for chemical modifications, such as methylation and acetylation. These chemical marks serve as “on” and “off” switches for specific genes.

Stewart discovered that the histone modifications that poise embryonic stem cell-specific genes for activation are also found on the histones near genes involved in regeneration, putting them into a ready-to-go state. “This suggests that two different gene expression programs may exist; one for normal cellular activity and one for regeneration,” explains Stewart. To test this hypothesis, the team looked at the histone marks during regeneration. As suspected, they saw a reduction in “off” switches and an increase in “on” switches in regenerating tissue, tipping the balance toward gene expression.

Delving deeper, the researchers found that enzymes that remove the “off” mark, so-called demethylases, are present in high levels in regenerating tissue. One enzyme in particular, called Kdm6b.1, is found exclusively in cells that are undergoing the regeneration process. Without Kdm6b.1, zebrafish failed to regenerate amputated fins, meaning removal of the “off” mark is a prerequisite for fin regeneration.

In the long term, the Salk researchers hope that these findings will help them understand whether we can affect the outcome of mammalian limb regeneration. In the more immediate future, the team plans to use global approaches to identify all the targets of Kdm6b.1 during regeneration, and to find out what gives the signal to turn these genes off when regeneration is complete.

In addition to Stewart and Izpisúa Belmonte, Zhi-Yang Tsun, also contributed to the study.

The study was funded in part by the California Institute for Regenerative Medicine, the Fundacion Cellex, the G. Harold and Leila Y. Mathers Charitable Foundation, the Ipsen Foundation, and the National Institutes of Health.

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Adapted from materials provided by Salk Institute, via EurekAlert!, a service of AAAS.

http://www.sciencedaily.com/releases/2009/11/091102171419.htm

“Longevity Genes” – Why Some of Us Live Longer

Scientists have long been baffled as to why some people live so much longer than others. Diet and exercise account for some of it, but researchers have found that genetics also factor heavily into the equation, and that long life is somewhat hereditary as it is with living bristlecone pine that were alive when Caesar ruled Rome.

However, centenarians are known to have just as many—and sometimes even more—harmful gene variants compared with those who die much younger. So what is the secret advantage? That’s a question the experts have been eager to find an answer to.

Scientists at the Albert Einstein College of Medicine of Yeshiva University have finally unlocked the secret behind the paradox. They were able to identify specific favorable “longevity genes” that offer protection from the harmful effects of “bad genes”. The discovery could lead to new drugs that protect against age related diseases.

“We hypothesized that people living to 100 and beyond must be buffered by genes that interact with disease-causing genes to negate their effects,” says Dr. Aviv Bergman, a professor in the departments of pathology and neuroscience at Einstein and senior author of the study.

To test the hypothesis, Dr. Bergman and his colleagues examined individuals enrolled in Einstein’s Longevity Genes Project, initiated in 1998 to investigate longevity genes in a selected population: Ashkenazi (Eastern European) Jews. They are descended from a founder group of just 30,000 or so people. So they are relatively genetically homogeneous, which makes it easier to associate traits (in this case, age-related diseases and longevity) with the genes that determine them.

Participating in the study were 305 Ashkenazi Jews more than 95 years old and a control group of 408 unrelated Ashkenazi Jews. (Centenarians are so rare in any human population—only one in 10,000 people live to be 100—that “longevity” genes probably wouldn’t turn up in a typical control group.)

All participants were grouped into cohorts representing each decade of lifespan from the 50’s on up. Using DNA samples, the researchers determined the prevalence in each cohort of 66 genetic markers present in 36 genes associated with aging.

As expected, some disease-related gene variants were as prevalent or even more prevalent in the oldest cohorts of Ashkenazi Jews than in the younger ones. And as Dr. Bergman had predicted, genes associated with longevity also became more common in each succeeding cohort.

“These results indicate that the frequency of deleterious genotypes may increase among people who live to extremely old ages because their protective genes allow these disease-related genes to accumulate,” says Dr. Bergman.

The Einstein researchers were able to construct a network of gene interactions that contributes to the understanding of longevity. In particular, they found that the favorable variant of the gene CETP acts to buffer the harmful effects of the disease-causing gene Lp(a).

If future research confirms that a single longevity gene can buffers against multiple disease-causing genes, then drugs that mimic the action of the gene could protect against a variety of cardiovascular disease and other age-related ailments.

Posted by Rebecca Sato

Related Galaxy posts:

Related Galaxy posts:
Can Humans Live to 1,000? Some Experts Claim We Can — Others Want to Prevent That
Video: Aubrey de Grey -Defeat of Aging

Links:

http://www.aecom.yu.edu/home/news/PRdetails.asp?isPR=1&id=372

http://vinnysa1store.blogspot.com/2007/08/einstein-researchers-use-novel-approach.html

http://www.dailygalaxy.com/my_weblog/2009/11/longevity-genes-why-some-of-us-live-longer.html

Scientists Launch Effort To Sequence The DNA Of 10,000 Vertebrates

Scientists involved in the Genome 10K Project are assembling specimens of thousands of animals spanning a broad range of evolutionary diversity. (Credit: Photos courtesy of San Diego Zoo)

Scientists have an ambitious new strategy for untangling the evolutionary history of humans and their biological relatives: Create a genetic menagerie made of the DNA of more than 10,000 vertebrate species. The plan, proposed by an international consortium of scientists, is to obtain, preserve, and sequence the DNA of approximately one species for each genus of living mammals, birds, reptiles, amphibians, and fish.

“Understanding the evolution of the vertebrates is one of the greatest detective stories in science,” said David Haussler, a Howard Hughes Medical Institute investigator at the University of California, Santa Cruz (UCSC). “No one has ever really known how the elephant got its trunk, or how the leopard got its spots. This project will lay the foundation for work that will answer those questions and many others.”

Known as the Genome 10K Project, the approximately $50 million initiative is “tremendously exciting science that will have great benefits for human and animal health,” Haussler said. “Within our lifetimes, we could get a glimpse of the genetic changes that have given rise to some of the most diverse life forms on the planet.”

Haussler is one of the lead authors of an article, published online November 5, 2009, in the Journal of Heredity, that outlines the project. The other lead authors include Stephen J. O’Brien, chief of the Laboratory of Genomic Diversity at the National Cancer Institute, and Oliver A. Ryder, director of genetics at the San Diego Zoo’s Institute for Conservation Research and adjunct professor of biology at the University of California, San Diego. Coauthors and additional authors, who together make up a group called the Genome 10K Community of Scientists (G10KCOS), include geneticists, paleontologists, ecologists, conservationists, and other scientists representing major zoos, museums, research centers, and universities around the world.

The proposal originated at a meeting Haussler hosted at UCSC in April 2009. More than 50 scientists came together to discuss the merits of the project and its daunting logistic and financial challenges. “Some of the people at the meeting were initially skeptical,” Haussler said. “But they quickly recognized the many advantages of a shared infrastructure and data analysis system.”

The primary impetus behind the proposal is the rapidly expanding capability of DNA sequencers and the associated decline in sequencing costs. “We’ll soon be in a situation where it will cost only a few thousand dollars to sequence a genome,” Haussler said. “At that point, most of the cost will be getting samples, managing the project, and handling data.”

All living vertebrates descend from a single marine species that lived 500-600 million years ago. Paleontologists do not know much about the physical appearance of that species, but because all of its descendents share certain characteristics, they know that it had segmented muscles, a forebrain, midbrain, and hind brain attached to spinal cord structures, and a sophisticated innate immune system.

That primitive vertebrate gave rise to what Haussler calls “one of the most spectacularly malleable branches of life.” Vertebrates spread throughout the oceans, conquered land, and eventually took to the air. Over the course of time they produced stunning innovations, including multichambered hearts, bones and teeth, an internal skeleton that has supported the largest aquatic and terrestrial animals on the planet, and a species of primate — Homo sapiens — that has produced sophisticated language, culture, and technology.

By sequencing the DNA of 10,000 vertebrates — roughly one-sixth of the 60,000 species estimated to be living today — biologists will be able to reconstruct the genetic changes that gave rise to this astonishing diversity. Some parts of our DNA are very similar to the DNA of other vertebrates, reflecting our descent from a common ancestor, while other parts are markedly different. “We can understand the function of elements in the human genome by seeing what parts of the genome have changed and what parts have not changed in humans and other animals,” said Haussler.

The project also will help conservation efforts by documenting the genomes and genetic diversity of threatened and endangered vertebrate species. By helping scientists predict how species will respond to climate change, pollution, emerging diseases, and invasive competitors, it will support the assessment, monitoring, and management of biological diversity.

The G10KCOS consortium has been developing guidelines for the collection, preservation, and documentation of cell lines and DNA samples. It also has been discussing potential public and private sources of funding for the project — estimated at $50 million if the price of handling and sequencing each DNA sample eventually falls to $5,000. Said Haussler: “How do you raise $50 million? Ask nicely and make a strong case.”

In planning the project, the G10KCOS group has used the Human Genome Project as a model. For example, the consortium plans to release sequencing data immediately according to standards developed for the sequencing of the human genome. Haussler also cited that project, which began before needed sequencing technologies were available, as evidence that it is worthwhile to begin planning for the Genome 10K Project before the cost of sequencing falls enough to make it feasible. “The time to start is now, or the job will get away from us,” said Haussler. “The sequencing machines will be waiting, but the samples won’t be ready.”

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Adapted from materials provided by Howard Hughes Medical Institute, via EurekAlert!, a service of AAAS.

http://www.sciencedaily.com/releases/2009/11/091104132706.htm

Darwin’s Wolf Mystery Solved

By Brandon Keim

Genetic analysis of the now-extinct Falkland Islands Wolf has answered a biological riddle that caught the attention of a young Charles Darwin, and helped shape his understanding of evolution.

During his voyage aboard the HMS Beagle, Darwin observed that the wolves — like his now-famous finches — varied widely in size between different islands, suggesting that the traits of species were not immutable, but changed over time in response to their environments.

Darwin also wondered at the origins of the wolves, which were unusually small, and had reddish fur and relatively short jaws. He dubbed them foxes, and was the first of many scientists to suspect that the strange canids weren’t wolves at all. Others thought they were descended from dogs brought by the islands’ first human settlers. Indeed, not a single mammal species other than the wolf was native to the Falkland Islands, located 300 miles off the southeastern tip of South America.

In a study published Tuesday in Current Biology, researchers address these questions with a genetic analysis of five museum specimens. Their findings are twofold. First, the specimens last shared a common ancestor 70,000 years ago, or a full 50,000 years before humans sailed to the Falklands; and the animals’ closest relative is the maned wolf, still found on the savannas of South America.

Moreover, the split from the maned wolf appears to have occurred 6.7 million years ago — some four million years before wolves are known to have lived in South America. At that time, maned wolves lived in North America, and it seems that all of South America’s canids originated in the north.

Unfortunately, by the time Darwin arrived in the Falklands, the wolves were being killed for their fur, and their numbers were in decline. “Within a very few years after these islands shall have become regularly settled, in all probability this fox will be classed with the dodo, as an animal which has perished from the face of the earth,” he wrote.

Forty years later, the Falklands Islands wolf was gone.

Image: From Zoology of the Voyage of the H.M.S. Beagle

See Also:

• Pink Iguana That Darwin Missed Holds Evolutionary Surprise
• Black Wolves the Result of Interbreeding With Dogs
• Evidence for Bone-Crushing Wolves Discovered

Citation: “Evolutionary history of the Falklands wolf.” By Graham J. Slater, Olaf Thalmann, Jennifer A. Leonard, Rena M. Schweizer, Klaus-Peter Koepfl, John P. Pollinger, Nicolas J. Rawlence, Jeremy J. Austin, Alan Cooper, and Robert K. Wayne. Current Biology, Vol. 19 Issue 20, November 3, 2009.

Brandon Keim’s Twitter stream and reportorial outtakes; Wired Science on Twitter. Brandon is currently working on a book about ecosystem and planetary tipping points.

http://www.wired.com/wiredscience/2009/11/darwins-wolf/

Early Life Hedged Its Bets to Survive

By Brandon Keim

By forcing bacteria to evolve in ever-changing conditions, scientists have induced a behavior in which colonies formed by microbes with identical genes take radically different forms, as if one sibling in a pair of identical quadruplets could sprout gills.

Technically known as “stochastic switching between phenotypic states” — or, more conversationally, hedging your bets — the ability may have been critical to the success of primitive forms of life.

Bet hedging “may have been among the earliest evolutionary solutions to life in variable environments,” even preceding the ability to turn genes on and off, wrote researchers in a study published Wednesday in Nature.

Scientists have known for decades about bet hedging, which is widespread in the natural world. One well-known example comes from disease-causing bacteria, which randomly produce different surface proteins, a few of which are bound to escape immune system detection. For all its ubiquity, however, bet-hedging behavior was at first considered counter-intuitive, even baffling. After all, in any given instance, it’s better to have the right surface protein.

But it’s not always possible to know what’s right in advance, especially in highly variable environments. In the 1960s, evolutionary biologists made mathematical models suggesting that bet hedging made sense over the long run. Some researchers even speculated that it was a basic component in the toolbox of early life, allowing primitive microbes to adapt rapidly, without being able to sense their environments or adjust gene activity — a sophisticated ability that probably took hundreds of millions of years to emerge.

But for all this theorizing, the evolution of bet-hedging had until now never been directly observed.

“Almost every biologist knows about this and is fascinated by it,” said study co-author Hubertus Beaumont, a Leiden University biologist. “We go one step further, and see this evolving in real time.”

Beaumont started the experiment with a population of genetically identical Pseudomonas fluorescens, a common bacterium that divides every 45 minutes and has a relatively small genome, making it easy to study.

From that strain, they seeded 12 different bacterial lines, each growing in a tube of undisturbed, nutrient-rich broth. After three days, a sample was taken and spread on agar plates to see what type of colonies formed. The bacteria divided and spread across each plate. The researchers then took a single sample of the healthiest colony and transferred it to a tube of shaken broth. After another three days of growth, the P. fluorescens in that tube were again sampled, spread on agar, and the healthiest put back into unshaken broth.

From a human perspective, it was as if tribes that thrived in a forest were suddenly tossed in a desert, then thrown back as soon as they’d started to adjust. The switch was performed a total of 16 times, with the researchers sequencing the survivors’ genomes at each step.

Earlier research by Paul Rainey, a Massey University evolutionary geneticist and co-author of the study, showed that different types of broth drove the evolution of different colony types. Shaken broth favored colonies that, in their aggregates of millions of microbes, had a smooth, rounded appearance. Unshaken conditions favored the evolution of wrinkled, fast-spreading colonies. As the rounds of selection continued, some P. fluorescens lines evolved back and forth between wrinkly and smooth types.

But in two of the lines, something special happened: In the very same tube, sharing the very same genetic inheritance, were cells that formed completely different types of colonies. Some were wrinkled, and others were smooth. It was as if those P. fluorescens strains had planned for an unpredictable future.

When the researchers looked at the genomic histories, they found that bet hedging required nine genetic mutations. The first eight were linked to traits that helped microbes survive in shaken and static tubes. The ninth, involving a gene important in metabolism, triggered the ability to produce multiple colony forms. The researchers ran the experiment multiple times, with similar results. An average of one line in twelve would evolve bet hedging, always as a result of the same accumulation of mutations.

This ability “could reasonably—one might think—take tens of thousands of generations to evolve,” wrote the researchers. Instead, it took a few months. That it emerged so rapidly hints at the role it may have played for microbes that hadn’t yet evolved ability to to sense changes in temperature or nutrient availability, much less respond to them.

“For them, the world was completely unpredictable,” said Beaumont. “I suspect that if you go back in time, you’d find organisms with one genotype that could express a wide range of strategies.”

Richard Lenski, a Michigan State University evolutionary biologist known for his decades-long studies of evolutionary dynamics in E. coli colonies, said that it’s difficult to know exactly what happened early in life’s history. “But their results do show that such adaptations evolve pretty easily, so it’s certainly possible,” said Lenski, who was not involved in the study.

As for what caused colonies to take radically different forms from their genetically identical neighbors, or why that ninth mutation in particular was so critical, Beaumont doesn’t yet know. Although we know the mutations, the details of the mechanisms underlying evolution, even in simple bacteria, are often “still hidden in a black box,” he said.

“We want to know what’s going on in that box,” said Beaumont. “We’re going beyond theory. We’re doing experiments with evolution itself.”

Image: Hubertus Beaumont

See Also:

• Early Life Didn’t Just Divide, It United
• Scientists Create a Form of Pre-Life
• Self-Replicating Chemicals Evolve Into Lifelike Ecosystem
• Life’s First Spark Re-Created in the Laboratory

Citation: “Experimental evolution of bet hedging.” Hubertus J. E. Beaumont, Jenna Gallie, Christian Kost, Gayle C. Ferguson & Paul B. Rainey. Nature, Vol. 461 No. 7269, November 4, 2009.

Brandon Keim’s Twitter stream and reportorial outtakes; Wired Science on Twitter. Brandon is currently working on a book about ecosystem and planetary tipping points.

http://www.wired.com/wiredscience/2009/11/bacteria-hedging/

Inefficient Selection: New Evolutionary Mechanism Accounts For Some Of Human Biological Complexity

Genomic and proteomic analysis has found a new evolutionary mechanism that accounts for some of the biological complexity of human beings. (Credit: iStockphoto/Liang Zhang)

A painstaking analysis of thousands of genes and the proteins they encode shows that human beings are biologically complex, at least in part, because of the way humans evolved to cope with redundancies arising from duplicate genes.

“We have found a specific evolutionary mechanism to account for a portion of the intricate biological complexity of our species,” said Ariel Fernandez, professor of bioengineering at Rice University. “It is a coping mechanism, a process that enables us to deal with the fitness consequences of inefficient selection. It enables some of our proteins to become more specialized over time, and in turn makes us more complex.”

Fernandez is the lead author of a paper slated to appear in the December issue of the journal Genome Research. The research is available online now.

Fernandez said the study drew from previous findings by his own research group and from seminal work of Michael Lynch, Distinguished Professor of Biology at Indiana University and a recently elected a fellow of the National Academy of Science. Lynch’s work has shown that natural selection is less efficient in humans as compared with simpler creatures like bacteria. This “selection inefficiency” arises from the smaller population size of humans as compared with unicellular organisms.

“In all organisms, genes get duplicated every so often, for reasons we don’t fully understand,” Fernandez said. “When working efficiently, natural selection eliminates many of these duplicates, which are called ‘paralogs.’ In our earlier work, we saw that an unusual number of gene duplicates had survived in the human genome, which makes sense given selection inefficiency in humans.”

In prior research on protein structure, Fernandez’s team found that some proteins are packaged more poorly than others. Moreover, they found that the least-efficiently packed proteins are structurally stable only when they bind with partner proteins to form complexes.

“These poorly packed proteins are potential troublemakers when gene duplication occurs,” Fernandez said. “The paralog encodes more copies of the protein than the body needs. This is called a ‘dosage imbalance,’ and it can make us sick. For instance, dosage imbalance has been implicated in Alzheimer’s and other diseases.”

Given selection inefficiency, Fernandez knew that paralogs encoding poorly packed proteins could remain in the human genome for quite a while. So he and graduate student Jianpeng Chen decided to examine whether gene duplicates had remained in the genome long enough for random genetic mutations to affect the paralogs dissimilarly. Fernandez and Chen, now a senior researcher in Beijing, China, cross-analyzed databases on genomics, protein structure, microRNA regulation and protein expression in such troublesome paralogs.

“The longer these duplicate genes stick around due to inefficient selection, the more likely they are to suffer a random mutation,” Fernandez said. “Portions of every gene act to regulate protein expression — by binding with microRNA, for example. We found numerous instances where random mutations had caused paralogs to be expressed dissimilarly, in ways that removed detrimental dosage imbalances.”

Lynch said one aspect of Fernandez’s research that is potentially groundbreaking is the observed tendency of proteins to evolve a more open structure in complex organisms.

“This observation fits with the general theory that large organisms with relatively small population sizes — compared to microbes — are subject to the vagaries of random genetic drift and hence the accumulation of very mildly deleterious mutations,” Lynch said.

In principle, he said, the accumulation of such mutations may encourage a slight breakdown in protein stability. This, in turn, opens the door to interactions with other proteins that can return a measure of that lost stability.

“These are the potential roots for the emergence of novel protein-protein interactions, which are the hallmark of evolution in complex, multicellular species,” Lynch said. “In other words, the origins of some key aspects of the evolution of complexity may have their origins in completely nonadaptive processes.”

Fernandez said the research reveals how increasingly specialized proteins can evolve. He drew an analogy to a business that hires two delivery drivers that initially cover the same parts of town but eventually specialize to deliver only to specific neighborhoods.

“Eventually, even if times become tough, you cannot lay off either of them because they each became so specialized that your company needs them both,” he said.

The more simple a creature is, the fewer specialized proteins it possesses. Humans and other higher-order mammals need many specialized proteins to build the specialized tissues in their skin, skeleton and organs. Even more specialized proteins are needed to maintain and regulate them. This complexity requires that the duplicates of the original jack-of-all-trades gene be retained, but this does not happen unless selection is inefficient. This is frequently a point of contention between proponents of evolution and intelligent design.

Fernandez and Chen looked at duplicate genes across the human genome and found that the more poorly packed a protein was, the more likely it was to be distinguished through paralog specialization.

“This supports the case for evolution because it shows that you can drive complexity with random mutations in duplicate genes,” Fernandez said. “But this also implies that random drift must prevail over Darwinian selection. In other words, if Darwinian selection were ruthlessly efficient in humans — as it is in bacteria and unicellular eukaryotes — then our level of complexity would not be possible.”

The research is supported by the National Institutes of Health.

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Journal reference:

 

1. Ariel Fernández, Jianping Chen. Human capacitance to dosage imbalance: Coping with inefficient selection. Genome Research, 2009; DOI: 10.1101/gr.094441.109

Adapted from materials provided by Rice University.

http://www.sciencedaily.com/releases/2009/11/091103145603.htm

New Insights Into Australia’s Unique Platypus

New insights into the biology of the platypus and echidna have been published, providing a collection of unique research data about the world’s only monotremes. (Credit: CSIRO)

New insights into the biology of the platypus and echidna have been published, providing a collection of unique research data about the world’s only monotremes.

University of Adelaide geneticist Dr Frank Grützner and his team have authored five of 28 papers which appear in two special issues of the Australian Journal of Zoology and Reproduction Fertility and Development.

The articles shed new light on the extraordinary complex platypus sex chromosome system.

“For the first time we have looked at how the 10 sex chromosomes find each other during sperm development in platypus,” Dr Grützner says.

“We discovered that a remarkably organised mechanism must exist in platypus, where sex chromosomes from one end pair first and then they go down the sex chromosome chain, just like a zipper. There is nothing random about it.”

Dr Grützner and his colleagues also isolated and analysed for the first time the sequence of the male-specific Y chromosomes.

“Previously we knew nothing about the Y chromosomes because only the female platypus genome was sequenced. The data we found has given us valuable clues about the evolution of Y chromosomes in all mammals, including humans,” Dr Grützner says.

All 28 published articles in the CSIRO journals have arisen from the Boden Research Conference, “Beyond the Platypus Genome,” hosted by the University of Adelaide in November 2008, which attracted researchers from around the world.

The published papers represent a wide range of monotreme research, from genome to field biology, population genetics and captive breeding, evolution to immunology, venom, sperm and milk in both the platypus and echidna.

“I expect these results to make a major impact in the field of monotreme research and mammal evolution,” Dr Grützner says.

“We have entered a new era in monotreme research, where we are seeing a more integrated approach using genomics, biochemistry and field biology to tackle important questions in monotreme biology. This knowledge will also help us conserve these iconic Australian mammals,” he says.

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Adapted from materials provided by University of Adelaide.

http://www.sciencedaily.com/releases/2009/11/091102111839.htm

The “DNA Pardon”: Murder Sentence Genetically Reduced

Gear up for Gattaca, as an Italian court has reduced a murderer’s sentence to account for his genes.  Despite the fact the relevant genetic science isn’t actually that advanced, the likely effects on the legal system, and the very real question of “Isn’t that ass backwards?”

A Mr Bayout stabbed a man to death for insulting his eye make-up in 2007.  These facts are not in doubt, and have been admitted by Mr Bayout himself.  The standard twelve year term was reduced by three years because of “psychiatric illness”, because when someone not only murders people for cosmetic reasons but is unbalanced and inclined towards doing it again, it’s important to get them back on the street as soon as possible.  But then Judge Reinotti of the Italian Court of Appeal cut another year off the sentence because of a “genetic abnormality” causing our killer to have low-levels of metabolizing enzyme monoamine oxidase A (MOAO).

Studies show that low levels of MOAO in abused children can lead to violent behavior.  And other studies show the opposite, accounting for some of the infinity of other factors which could influence this.  And there’s the fact that the entire science of behavioral genetics is nowhere near the point of being used in society and sentencing, unless you have lawyer who’s throwing everything possible at a judge in order to reduce the conviction.
But even suppose you had a perfect genetic program which could pinpoint what a person will do (which would be a hell of a trick because genes don’t even remotely work like that):  if your lawyer proves that your genes make you more likely to suddenly, insanely lose your mind and shove a knife into another human being until they die, that doesn’t sound like something that should reduce your sentence.  If someone proves in a court of law that you cannot help but kill people, that your very genes lead to murder, wouldn’t the only sane response is to make sure that your genes aren’t walking around any more?

Luke McKinneySentence Reduced – http://www.nature.com/news/2009/091030/full/news.2009.1050.html?s=news_rss

http://www.dailygalaxy.com/my_weblog/2009/11/the-dna-pardon-murder-sentence-genetically-reduced.html