 |
|
Computational biochemist uncovers a molecular clue to evolution
September 11, 2008TALLAHASSEE, Fla. -- A Florida State University researcher who uses high-powered computers to map the workings of proteins has uncovered a mechanism that gives scientists a better understanding of how evolution occurs at the molecular level.
Such an understanding eventually could lead to the development of new and more effective antiparasitic drugs.
Wei Yang is an assistant professor in FSU's Department of Chemistry and Biochemistry and a faculty member in the university's Institute of molecular biophysics. Working with colleagues from FSU, Duke University and Brandeis University, he recently produced remarkable computer models of an enzyme that carries the unwieldy name of inosine monophosphate dehrydrogenase, or IMPDH for short. IMPDH is responsible for initiating certain metabolic processes in DNA and RNA, enabling the biological system to reproduce quickly.
"In creating these simulations of IMPDH, we observed something that hadn't been seen before," Yang said. "Previously, enzymes were believed to have a single 'pathway' through which they deliver catalytic agents to biological cells in order to bring about metabolic changes. But with IMPDH, we determined that there was a second pathway that also was used to cause these chemical transformations. The second pathway didn't operate as efficiently as the first one, but it was active nevertheless."
Why would an enzyme have two pathways dedicated to the same task? Yang and his colleagues believe that the slower pathway is an evolutionary vestige left over from an ancient enzyme that evolved over eons into modern-day IMPDH.
The finding is significant for several reasons, Yang said.
"First of all, this offers a rare glimpse of evolutionary processes at work on the molecular level," Yang said. "Typically when we talk about evolution, we're referring to a process of adaptation that occurs in a population of organisms over an extended period of time. Our research examines such adaptations at the most basic level, which helps scientists to develop a fuller picture of how evolution actually occurs.
"This also represents a big step forward in our efforts to create computational simulations of biological processes," Yang said. "In this case, we first made a prediction of the enzyme structure via computer and later verified it through direct observation in a laboratory, rather than the other way around. This is a most unusual accomplishment, and one that indicates we are becoming more advanced in our ability to answer questions relating to biological functions at the molecular level."
"Because of the key role that IMPDH plays, scientists have focused on developing new antiparasitic drugs that target it," Yang said. "Our research will certainly contribute to this process."
Joseph Schlenoff, the chairman of FSU's Department of Chemistry and Biochemistry, praised Yang's computational methods as "extremely powerful because they are rigorous, make few assumptions and approximate the complexity of the real world. The accurate predictions that result represent success that has been promised to us for so long by scientists using computers."
Collaborating with Yang on the project were Gavin J.P. Naylor, an associate professor in FSU's Department of Scientific Computing; Donghong Min, a postdoctoral associate in the Institute of Molecular Physics; Hongzhi Li, a former postdoc in the Institute of Molecular Physics; Clemens Lakner, a graduate assistant in the Department of Biological Science; David Swofford, a research scientist at Duke University and former FSU faculty member; Lizbeth Hedstrom, a professor of biochemistry at Brandeis University; and postdocs Helen R. Josephine and Iaian S. MacPherson, both of Brandeis.
Together the researchers wrote about their findings in a paper, "An Enzymatic Atavist Revealed in Dual Pathways for Water Activation," that was published this summer in PLoS Biology, a peer-reviewed, open-access journal published by the Public Library of Science. Visit http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0060206 to read the paper.
Dan Herschlag, a professor of biochemistry at Stanford University, edited the paper for PLoS Biology. He praised it for its innovative approach.
"This work reveals basic aspects of how enzymes work and how they have evolved," Herschlag said. "The study melds experiment and computation in a powerful fashion and represents a model for how to use interdisciplinary research to answer important questions."
Florida State University
"In creating these simulations of IMPDH, we observed something that hadn't been seen before," Yang said. "Previously, enzymes were believed to have a single 'pathway' through which they deliver catalytic agents to biological cells in order to bring about metabolic changes. But with IMPDH, we determined that there was a second pathway that also was used to cause these chemical transformations. The second pathway didn't operate as efficiently as the first one, but it was active nevertheless."
Why would an enzyme have two pathways dedicated to the same task? Yang and his colleagues believe that the slower pathway is an evolutionary vestige left over from an ancient enzyme that evolved over eons into modern-day IMPDH.
The finding is significant for several reasons, Yang said.
"First of all, this offers a rare glimpse of evolutionary processes at work on the molecular level," Yang said. "Typically when we talk about evolution, we're referring to a process of adaptation that occurs in a population of organisms over an extended period of time. Our research examines such adaptations at the most basic level, which helps scientists to develop a fuller picture of how evolution actually occurs.
"This also represents a big step forward in our efforts to create computational simulations of biological processes," Yang said. "In this case, we first made a prediction of the enzyme structure via computer and later verified it through direct observation in a laboratory, rather than the other way around. This is a most unusual accomplishment, and one that indicates we are becoming more advanced in our ability to answer questions relating to biological functions at the molecular level."
"Because of the key role that IMPDH plays, scientists have focused on developing new antiparasitic drugs that target it," Yang said. "Our research will certainly contribute to this process."
Joseph Schlenoff, the chairman of FSU's Department of Chemistry and Biochemistry, praised Yang's computational methods as "extremely powerful because they are rigorous, make few assumptions and approximate the complexity of the real world. The accurate predictions that result represent success that has been promised to us for so long by scientists using computers."
Collaborating with Yang on the project were Gavin J.P. Naylor, an associate professor in FSU's Department of Scientific Computing; Donghong Min, a postdoctoral associate in the Institute of Molecular Physics; Hongzhi Li, a former postdoc in the Institute of Molecular Physics; Clemens Lakner, a graduate assistant in the Department of Biological Science; David Swofford, a research scientist at Duke University and former FSU faculty member; Lizbeth Hedstrom, a professor of biochemistry at Brandeis University; and postdocs Helen R. Josephine and Iaian S. MacPherson, both of Brandeis.
Together the researchers wrote about their findings in a paper, "An Enzymatic Atavist Revealed in Dual Pathways for Water Activation," that was published this summer in PLoS Biology, a peer-reviewed, open-access journal published by the Public Library of Science. Visit http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0060206 to read the paper.
Dan Herschlag, a professor of biochemistry at Stanford University, edited the paper for PLoS Biology. He praised it for its innovative approach.
"This work reveals basic aspects of how enzymes work and how they have evolved," Herschlag said. "The study melds experiment and computation in a powerful fashion and represents a model for how to use interdisciplinary research to answer important questions."
Florida State University
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 |