 |
|
Mysterious snippets of DNA withstand eons of evolution, Stanford study
October 02, 2008STANFORD, Calif. - Small stretches of seemingly useless DNA harbor a big secret, say researchers at the Stanford University School of Medicine. There's one problem: We don't know what it is. Although individual laboratory animals appear to live happily when these genetic ciphers are deleted, these snippets have been highly conserved throughout evolution.
"The true function of these regions remains a mystery, but it's clear that the genome really does need and use them," said Gill Bejerano, PhD, assistant professor of developmental biology and of computer science. In fact, these so-called "ultraconserved" regions are about 300 times less likely than other regions of the genome to be lost during mammalian evolution, according to research from Bejerano and graduate student Cory McLean to be published in the Oct. 2 issue of Genome Research.
Although some of the ultraconserved regions, which were first identified by Bejerano in 2004, are involved in the regulation of the expression of neighboring genes, previous research has shown that mice missing each of four regions seem perfectly normal.
"It's very surprising that none of the four has any observable phenotype," said Bejerano. "In some ways it just doesn't make sense."
This lack of effect is usually taken as a strong argument against an important functional role for the missing segments of DNA - either because they don't do much or because other bits of DNA serve as understudies when the primary actors are missing. But in this most recent study, evolution roars over the squeak of the seemingly contented mice.
"When we tried to determine whether similar deletions occur in the wild," said Bejerano, "we found that this is almost never seen in nature."
McLean and Bejerano compared the likelihood that ultraconserved elements of at least 100 base pairs shared by humans, macaques and dogs would have been deleted in rats and mice, with the likelihood of a similar pattern in non-conserved DNA. Less than one-tenth of 1 percent of segments completely identical among the primates and dog were missing in the rodents. In contrast, about 25 percent of non-conserved segments were absent in the mice and rats.
It's not that these regions are somehow protected against change: they are mutated in about one in 200 healthy humans. Rather, these changes seem to be swept away over time by the tides of evolution in a process called "purifying selection." Bejerano and McLean believe that something similar may be happening in the laboratory mice on a scale too subtle to be seen under carefully controlled experimental conditions.
After establishing how infrequently the ultraconserved segments are deleted, the researchers investigated whether the degree of homology (the percent of nucleotides shared between species) or the extent of conservation (the evolutionary distance between species that share a version of the sequence) correlated most closely with the likelihood that it would be lost in primates or rodents. Sequences shared among many distantly related species are likely to be older than sequences found only in closely related species. The researchers found that less-highly conserved sequences shared among several distantly related species - including opossum, platypus, chicken, frog and fish - are more likely to also occur in humans than are more-homologous sequences that occur in only a few closely related species. The likelihood that a sequence will be found in humans increases as the evolutionary age of the sequence increases.
"Interestingly," said Bejerano, "the longer the sequence has been in us, the less likely it is to be lost. It's almost like the bricks in the foundation of a building, which hold up the rest of the structure."
Clearly there remains a lot to be discovered. The upcoming availability of several additional well-sequenced mammalian genomes will give the researchers even more data with which to work. And subjecting the laboratory mice missing the ultraconserved regions to a variety of conditions, such as changes in diet or living conditions, may make more noticeable any differences between them and the mice without changes.
"Evolution is a lot of fun," said Bejerano, who plans to continue the investigation into what the ultraconserved segments might be doing. "You answer one question, and five others pop up. But one of the most rewarding things to me is the fact that we're developing a growing appreciation for how much these regions actually matter."
Stanford University Medical Center
"It's very surprising that none of the four has any observable phenotype," said Bejerano. "In some ways it just doesn't make sense."
This lack of effect is usually taken as a strong argument against an important functional role for the missing segments of DNA - either because they don't do much or because other bits of DNA serve as understudies when the primary actors are missing. But in this most recent study, evolution roars over the squeak of the seemingly contented mice.
"When we tried to determine whether similar deletions occur in the wild," said Bejerano, "we found that this is almost never seen in nature."
McLean and Bejerano compared the likelihood that ultraconserved elements of at least 100 base pairs shared by humans, macaques and dogs would have been deleted in rats and mice, with the likelihood of a similar pattern in non-conserved DNA. Less than one-tenth of 1 percent of segments completely identical among the primates and dog were missing in the rodents. In contrast, about 25 percent of non-conserved segments were absent in the mice and rats.
It's not that these regions are somehow protected against change: they are mutated in about one in 200 healthy humans. Rather, these changes seem to be swept away over time by the tides of evolution in a process called "purifying selection." Bejerano and McLean believe that something similar may be happening in the laboratory mice on a scale too subtle to be seen under carefully controlled experimental conditions.
After establishing how infrequently the ultraconserved segments are deleted, the researchers investigated whether the degree of homology (the percent of nucleotides shared between species) or the extent of conservation (the evolutionary distance between species that share a version of the sequence) correlated most closely with the likelihood that it would be lost in primates or rodents. Sequences shared among many distantly related species are likely to be older than sequences found only in closely related species. The researchers found that less-highly conserved sequences shared among several distantly related species - including opossum, platypus, chicken, frog and fish - are more likely to also occur in humans than are more-homologous sequences that occur in only a few closely related species. The likelihood that a sequence will be found in humans increases as the evolutionary age of the sequence increases.
"Interestingly," said Bejerano, "the longer the sequence has been in us, the less likely it is to be lost. It's almost like the bricks in the foundation of a building, which hold up the rest of the structure."
Clearly there remains a lot to be discovered. The upcoming availability of several additional well-sequenced mammalian genomes will give the researchers even more data with which to work. And subjecting the laboratory mice missing the ultraconserved regions to a variety of conditions, such as changes in diet or living conditions, may make more noticeable any differences between them and the mice without changes.
"Evolution is a lot of fun," said Bejerano, who plans to continue the investigation into what the ultraconserved segments might be doing. "You answer one question, and five others pop up. But one of the most rewarding things to me is the fact that we're developing a growing appreciation for how much these regions actually matter."
Stanford University Medical Center
Evolution Current Events and Evolution News RSSHuman genomics in China
Ten years ago, the Chinese National Human Genome Center at Shanghai (South Center, hereafter) was established in the Zhangjiang HiTech Park of Pudong District in Shanghai. To commemorate this important event, which marks the beginning of the Genomics Era in China, we specially organize a series of mini-reviews for this special issue.
Avian flu becoming more resistant to antiviral drugs, says University of Colorado study
A new University of Colorado at Boulder study shows the resistance of the avian flu virus to a major class of antiviral drugs is increasing through positive evolutionary selection, with researchers documenting the trend in more than 30 percent of the samples tested.
Spookfish uses mirrors for eyes
A remarkable new discovery shows the four-eyed spookfish to be the first vertebrate ever found to use mirrors, rather than lenses, to focus light in its eyes.
Study Yields Clues About the Evolution of Epilepsy
Two children have a seizure. One child never has another seizure. Twenty years later, the other child has a series of seizures and is diagnosed with epilepsy. A study being led by researchers at Rensselaer Polytechnic Institute is looking at what could possibly happen in the development of these two children that would lead to such extreme variations in their neurologic health.
Plant polymerases IV and V are special forms of Polymerase II
It's a little like finding out that Superman is actually Clark Kent. A team of biologists at Washington University in St. Louis has discovered that two vital cellular components, nuclear RNA Polymerases IV and V (Pol IV and V), found only in plants, are actually specialized forms of RNA Polymerase II, an essential enzyme of all eukaryotic organisms, including humans.
Four, three, two, one . . . pterosaurs have lift off
Pterosaurs have long suffered an identity crisis. Pop culture heedlessly -- and wrongly -- lumps these extinct flying lizards in with dinosaurs. Even paleontologists assumed that because the creatures flew, they were birdlike in many ways, such as using only two legs to take flight.
Research team reports how, when life on Earth became so big
In 3.5 billion years, life on earth went from single microscopic cells to giant sequoias and blue whales. Scientists have now documented quantitatively that the increase in maximum size of organisms was not gradual, but happened in two distinct bursts "tied to the geological evolution of the planet," said Michal Kowalewski, professor of geosciences at Virginia Tech.
Snails and humans use same genes to tell right from left
Biologists have tracked down genes that control the handedness of snail shells, and they turn out to be similar to the genes used by humans to set up the left and right sides of the body.
CSHL scientists discover new way in which ubiquitin modifies transcriptional machinery to regulate gene activity
During gene transcription - the process inside the nucleus of cells by which DNA, the genetic material, is copied into RNA - a large, ever-changing multiprotein complex is enlisted to assist the DNA-copying enzyme in its challenging job.
No quick or easy technological fix for climate change, researchers say
Global warming, some have argued, can be reversed with a large-scale "geoengineering" fix, such as having a giant blimp spray liquefied sulfur dioxide in the stratosphere or building tens of millions of chemical filter systems in the atmosphere to filter out carbon dioxide.
More Evolution Current Events and Evolution News Articles
 | Why Evolution Is True by Jerry A. Coyne Why evolution is more than just a theory: it is a factIn all the current highly publicized debates about creationism and its descendant “intelligent design,” there is an element of the controversy that is rarely mentioned—the evidence, the empirical truth of evolution by natural selection. Even Richard Dawkins and Stephen Jay Gould, while extolling the beauty of evolution and examining case... |
| Dr. Gundry's Diet Evolution: Turn Off the Genes That Are Killing You and Your Waistline by Steven R. Dr Gundry YOUR GENES ARE TRYING TO KILL YOU– AND YOU’RE EATING IT UP!Does losing weight and staying healthy feel like a battle? Well, it’s really a war. Your enemies are your own genes, backed by millions of years of evolution, and the only way to win is to outsmart them.Dr. Steven Gundry explains what your body is “thinking” and tells you why, surprisingly, your genes actually “want” you to... | |
 | Thank God for Evolution: How the Marriage of Science and Religion Will Transform Your Life and Our World by Michael Dowd Abridged CDs • 8 CDs, 9 hours A revolutionary perspective on the relationship between religion and science that builds a bridge between people of all... |
 | Evolution by Douglas J. Futuyma In its scope and emphases, Evolution is a readily recognized descendant of the author's previous textbook, Evolutionary Biology. However, it is much shorter and is exclusively directed toward an undergraduate audience. Teachers and students will find the list of important concepts and terms in each chapter a helpful guide, and will appreciate the radically different dynamic figures and lively... |
 | Evolution for Everyone: How Darwin's Theory Can Change the Way We Think About Our Lives by David Sloan Wilson What is the biological reason for gossip?For laughter? For the creation of art?Why do dogs have curly tails?What can microbes tell us about morality?These and many other questions are tackled by renowned evolutionist David Sloan Wilson in this witty and groundbreaking new book. With stories that entertain as much as they inform, Wilson outlines the basic principles of evolution and shows how,... |
 | Evolution: What the Fossils Say and Why It Matters by Donald R. Prothero Over the past twenty years, paleontologists have made tremendous fossil discoveries, including fossils that mark the growth of whales, manatees, and seals from land mammals and the origins of elephants, horses, and rhinos. Today there exists an amazing diversity of fossil humans, suggesting we walked upright long before we acquired large brains, and new evidence from molecules that enable... |
 | The Edge of Evolution: The Search for the Limits of Darwinism by Michael J. Behe When Michael J. Behe's first book, Darwin's Black Box, was published in 1996, it launched the intelligent design movement. Critics howled, yet hundreds of thousands of readers -- and a growing number of scientists -- were intrigued by Behe's claim that Darwinism could not explain the complex machinery of the cell.Now, in his long-awaited follow-up, Behe presents far more than a challenge to... |
 | Radical Evolution: The Promise and Peril of Enhancing Our Minds, Our Bodies -- and What It Means to Be Human by Joel Garreau Taking us behind the scenes with today’s foremost researchers and pioneers, bestselling author Joel Garreau shows that we are at a turning point in history. At this moment we are engineering the next stage of human evolution. Through advances in genetic, robotic, information, and nanotechnologies, we are altering our minds, our memories, our metabolisms, our personalities, our progeny–and... |
 | Only a Theory: Evolution and the Battle for America's Soul by Kenneth R. Miller A leading scientist examines the battle between evolution and Intelligent Design in America At the dawn of the twenty- first century, the debate over Darwin’s theory of evolution is nearly as contentious as it was in the notorious Scopes trial a century ago. Today, however, people who believe that evolution is “only a theory” have put their hopes in a concept known as Intelligent Design. In... |
 | An Introduction to Biological Evolution by Kenneth V. Kardong Written for a general college audience, this book offers an introduction to the principles and significance of Darwinian evolution. It differs from most other textbooks on evolution in three fundamental ways: First, it is intended for students taking evolution early in their studies. Second, it examines the intellectual significance of Darwinian evolution. Third, the text departs from the... |
| © 2009 BrightSurf.com |