 |
|
Charting ever-changing genomes
July 20, 2007La Jolla, CA -- Instead of immutable proprietary software, any species' genetic information resembles open source code that is constantly tweaked and optimized to meet the users' specific needs. But which parts of the code have withstood the test of time and which parts have undergone rapid evolutionary change has been difficult to assess.
An international collaboration by researchers at the Salk Institute for Biological Studies, the University of Chicago, and the Max-Planck Institute for Developmental Biology developed a simple method to comb whole genomes for all the software fixes and security patches accumulated over time. In a first trial run, the scientists catalogued the genetic variations in 23 strains of the mustard weed Arabidopsis thaliana that were collected from the wild all over the world.
"Our study represents one of the first whole genome scans for levels and patterns of genetic variation within a species," says Joseph R. Ecker, Ph.D., professor in the Plant Biology Laboratory and director of the Salk Institute Genomic Analysis Laboratory, who led the current study published in last week's online edition of the Proceedings of the National Academy of Science. "It reveals the regions that are currently targeted by natural selection or have been so during the evolutionary past."
In an independent study the collaborators -- this time led by Detlef Weigel, Ph.D., director of the Max Planck Institute for Developmental Biology in Tübingen, Germany, and an adjunct professor at the Salk Institute -- went through the genomes of 20 different strains of Arabidopsis thaliana with an even finer-toothed comb, allowing them to determine the exact nature of the changes. The findings of the second study are published in the July 20 issue of the journal Science.
"We found that one out of 10 genes is very different," says Weigel. "This plasticity is truly surprising for a genome that's very streamlined and unlike bigger genomes doesn't contain a lot of junk DNA," he adds.
A decade ago, Arabidopsis was widely adopted by plant scientists as an easily manipulated model for other plants because it is simple to grow in the laboratory, has a short life cycle and a small genome. Compared to corn, which might have as many as 2.5 billion base pairs of DNA and the human genome with roughly 3 billion pairs, Arabidopsis only has about 120 million base pairs of DNA.
With nowhere to run, plants are under constant threat from heat, cold, high acidity or salinity, or pathogens such as viruses and leaf-munching insects. In response, plants mobilize physiological and biochemical defenses that help them survive. "We expected certain classes of genes to be highly variable due to natural selection in different environments. Both studies revealed precisely which gene family members indeed were shaped by evolution," says Justin Borevitz, Ph.D., a former post-doctoral researcher in the Ecker lab and now an assistant professor in the Department of Ecology and Evolution at the University of Chicago.
As a general rule, genes that don't change over time are under strong negative selection because they perform important housekeeping functions, while genes that vary widely such as disease resistance genes are under strong positive selection. "We covered both ends of the spectrum and ended up with a top list of no changes and a top list of a lot of changes," explains Borevitz. "All the data have been placed in a publicly accessible database and now researchers everywhere can look up their favorite genes."
To assemble their lists, the Ecker team poured over data derived from old-fashioned gene-chip technology, in which 25 nucleotide-long samples of every gene expressed in an Arabidopsis cell are spotted onto a tiny glass slide known as a microarray. The chopped up genomes of the different strains were then allowed to bind to their immobilized counterparts. Reduced hybridization resulted in a signal telling the researchers which regions the genomes differed from the fully sequenced reference strain.
"This method is simple and relatively inexpensive and can be applied to any organism whose whole genome has been sequenced and for which a gene array is available or can be easily made," explains Ecker. "For these reasons it is attractive to a wide audience practicing evolutionary genomics."
Weigel's team went a step further and effectively re-sequenced whole genomes with the help of nearly a billion 25-mers tiled on 5 large arrays that cover every possible nucleotide exchange on both strands of DNA. The high-resolution approach revealed a high number of specific changes in genes belonging to the so-called F-box superfamily, whose members plays a crucial part in flagging proteins for degradation.
"As highlighted by both studies, many genes that harbor major-effect changes in wild populations are likely to mediate interactions with the environment," says Weigel. "Ultimately, experiments under more natural conditions will be required to fully appreciate the functional relevance of such sequence variation."
Salk Institute
In an independent study the collaborators -- this time led by Detlef Weigel, Ph.D., director of the Max Planck Institute for Developmental Biology in Tübingen, Germany, and an adjunct professor at the Salk Institute -- went through the genomes of 20 different strains of Arabidopsis thaliana with an even finer-toothed comb, allowing them to determine the exact nature of the changes. The findings of the second study are published in the July 20 issue of the journal Science.
"We found that one out of 10 genes is very different," says Weigel. "This plasticity is truly surprising for a genome that's very streamlined and unlike bigger genomes doesn't contain a lot of junk DNA," he adds.
A decade ago, Arabidopsis was widely adopted by plant scientists as an easily manipulated model for other plants because it is simple to grow in the laboratory, has a short life cycle and a small genome. Compared to corn, which might have as many as 2.5 billion base pairs of DNA and the human genome with roughly 3 billion pairs, Arabidopsis only has about 120 million base pairs of DNA.
With nowhere to run, plants are under constant threat from heat, cold, high acidity or salinity, or pathogens such as viruses and leaf-munching insects. In response, plants mobilize physiological and biochemical defenses that help them survive. "We expected certain classes of genes to be highly variable due to natural selection in different environments. Both studies revealed precisely which gene family members indeed were shaped by evolution," says Justin Borevitz, Ph.D., a former post-doctoral researcher in the Ecker lab and now an assistant professor in the Department of Ecology and Evolution at the University of Chicago.
As a general rule, genes that don't change over time are under strong negative selection because they perform important housekeeping functions, while genes that vary widely such as disease resistance genes are under strong positive selection. "We covered both ends of the spectrum and ended up with a top list of no changes and a top list of a lot of changes," explains Borevitz. "All the data have been placed in a publicly accessible database and now researchers everywhere can look up their favorite genes."
To assemble their lists, the Ecker team poured over data derived from old-fashioned gene-chip technology, in which 25 nucleotide-long samples of every gene expressed in an Arabidopsis cell are spotted onto a tiny glass slide known as a microarray. The chopped up genomes of the different strains were then allowed to bind to their immobilized counterparts. Reduced hybridization resulted in a signal telling the researchers which regions the genomes differed from the fully sequenced reference strain.
"This method is simple and relatively inexpensive and can be applied to any organism whose whole genome has been sequenced and for which a gene array is available or can be easily made," explains Ecker. "For these reasons it is attractive to a wide audience practicing evolutionary genomics."
Weigel's team went a step further and effectively re-sequenced whole genomes with the help of nearly a billion 25-mers tiled on 5 large arrays that cover every possible nucleotide exchange on both strands of DNA. The high-resolution approach revealed a high number of specific changes in genes belonging to the so-called F-box superfamily, whose members plays a crucial part in flagging proteins for degradation.
"As highlighted by both studies, many genes that harbor major-effect changes in wild populations are likely to mediate interactions with the environment," says Weigel. "Ultimately, experiments under more natural conditions will be required to fully appreciate the functional relevance of such sequence variation."
Salk Institute
Genomes Current Events and Genomes News RSSScience teams at Cold Spring Harbor Laboratory identify 13 new tumor-suppressor genes in liver cancer
Over the years, hunting for cancer-related genes and understanding how they work has been an important, although time-consuming, exercise. At Cold Spring Harbor Laboratory (CSHL), five different research groups have now combined their expertise to speed up the rate of discovering cancer-related genes and validating their function in living animals.
Australian first: Kangaroo genome mapped
Australian researchers will today launch the world first detailed map of the kangaroo genome, completing the first phase of the kangaroo genomics project.
Yale researchers unravel mystery of brain aneurysms
Yale researchers have taken the first critical steps in unraveling the mysteries of brain aneurysms, the often fatal rupturing of blood vessels that afflicts 500,000 people worldwide each year and nearly killed Vice President-elect Joseph Biden two decades ago.
Social interactions can alter gene expression in the brain, and vice versa
Our DNA determines a lot about who we are and how we play with others, but recent studies of social animals (birds and bees, among others) show that the interaction between genes and behavior is more of a two-way street than most of us realize.
Washington University scientists first to sequence genome of cancer patient
For the first time, scientists have decoded the complete DNA of a cancer patient and traced her disease - acute myelogenous leukemia - to its genetic roots.
DNA chunks, chimps and humans
Researchers have carried out the largest study of differences between human and chimpanzee genomes, identifying regions that have been duplicated or lost during evolution of the two lineages.
Death by hyperdisease
It took less than a decade for native rats to become extinct on the Indian Ocean's previously uninhabited Christmas Island once Eurasian black rats jumped ship onto the island at the turn of the 20th century.
'Junk' DNA proves functional
In a paper published in Genome Research on Nov. 4, scientists at the Genome Institute of Singapore (GIS) report that what was previously believed to be "junk" DNA is one of the important ingredients distinguishing humans from other species.
UC Davis researchers discover a key to aggressive breast cancer
In trying to find out why HER2-positive breast cancer can be more aggressive than other forms of the disease, UC Davis Cancer Center researchers have surprisingly discovered that HER2 itself is the culprit. By shutting down its own regulator gene, HER2 creates a permissive environment for tumor growth.
Mapping a clan of mobile selfish genes
Much of human DNA is the genetic equivalent of e-mail spam: short repeated sequences that have no obvious function other than making more of themselves.
More Genomes Current Events and Genomes News Articles
 | Genome: The Autobiography of a Species in 23 Chapters (P.S.) by Matt Ridley The genome's been mapped. But what does it mean? Arguably the most significant scientific discovery of the new century, the mapping of the twenty-three pairs of chromosomes that make up the human genome raises almost as many questions as it answers. Questions that will profoundly impact the way we think about disease, about longevity, and about free will. Questions that will affect the rest... |
 | Genetics: From Genes to Genomes (3rd Edition Study Guide) by Leland Hartwell, Leroy Hood, Michael L. Goldberg, Ann E. Reynolds, Lee M. Silver, Ruth C. Veres Genetics: From Genes to Genomes is a cutting-edge, introductory genetics text authored by an unparalleled author team, including Nobel Prize winner, Leland Hartwell. The Second Edition continues to build upon the integration of Mendelian and molecular principles, providing students with the links between early genetics understanding and the new molecular discoveries that have changed the way... |
 | Short Guide to the Human Genome by Stewart Scherer How many genes are in the human genome? Which genes are commonly associated with genetic diseases? How many mobile elements, simple sequence repeats, or protein kinases are encoded in the genome? What are the largest genes and proteins? How similar are human proteins to those of mouse, yeast, or bacteria? Although the human genome has been sequenced, it often can be surprisingly difficult to... |
 | A Life Decoded: My Genome: My Life by J. Craig Venter The triumphant true story of the man who achieved one of the greatest feats of our era—the mapping of the human genome Growing up in California, Craig Venter didn’t appear to have much of a future. An unremarkable student, he nearly flunked out of high school. After being drafted into the army, he enlisted in the navy and went to Vietnam, where the life and death struggles he encountered as... |
 | The Genome War: How Craig Venter Tried to Capture the Code of Life and Save the World by James Shreeve The long-awaited story of the science, the business, the politics, the intrigue behind the scenes of the most ferocious competition in the history of modern science—the race to map the human genome.On May 10, 1998, biologist Craig Venter, director of the Institute for Genomic Research, announced that he was forming a private company that within three years would unravel the complete genetic... |
 | Genomes and What to Make of Them by Barry Barnes, John Dupre The announcement in 2003 that the Human Genome Project had completed its map of the entire human genome was heralded as a stunning scientific breakthrough: our first full picture of the basic building blocks of human life. Since then, boasts about the benefits—and warnings of the dangers—of genomics have remained front-page news, with everyone agreeing that genomics has the potential to... |
 | Welcome to the Genome: A User's Guide to the Genetic Past, Present, and Future by Rob DeSalle, Michael Yudell, American Museum of Natural History A thrilling "user's guide" to the genomics era Welcome to the genome, the miraculous blueprint of your DNA, coiled tight as a spring in the nucleus of each cell of your body. If unwound, the DNA from just one cell, while only a molecule in width, would stretch six feet in length! The information stored in its double helix structure - three billion bits worth - could fill 142 Manhattan... |
 | From Genes to Genomes: Concepts and Applications of DNA Technology by Jeremy Dale, Malcolm von Schantz Rapid advances in a collection of techniques referred to as gene technology, genetic engineering, recombinant DNA technology and gene cloning have pushed molecular biology to the forefront of the biological sciences. This new edition of a concise, well-written textbook introduces key techniques and concepts involved in cloning genes and in studying their expression and variation. The book... |
 | The Regulatory Genome: Gene Regulatory Networks In Development And Evolution by Eric H. Davidson Gene regulatory networks are the most complex, extensive control systems found in nature. The interaction between biology and evolution has been the subject of great interest in recent years. The author, Eric Davidson, has been instrumental in elucidating this relationship. He is a world renowned scientist and a major contributor to the field of developmental biology. The Regulatory Genome... |
 | A Primer of Genome Science, Third Edition by Gibson, Muse |
| © 2008 BrightSurf.com |