Scientists Find a Fingerprint of Evolution Across the Human GenomeApril 09, 2008Splicing exerts selective pressure on DNA sequence Cold Spring Harbor, NY -The Human Genome Project revealed that only a small fraction of the 3 billion "letter" DNA code actually instructs cells to manufacture proteins, the workhorses of most life processes. This has raised the question of what the remaining part of the human genome does. How much of the rest performs other biological functions, and how much is merely residue of prior genetic events? Scientists from Cold Spring Harbor Laboratory (CSHL) and the University of Chicago now report that one of the steps in turning genetic information into proteins leaves genetic fingerprints, even on regions of the DNA that are not involved in coding for the final protein. They estimate that such fingerprints affect at least a third of the genome, suggesting that while most DNA does not code for proteins, much of it is nonetheless biologically important - important enough, that is, to persist during evolution. Conservation of genetic information To gauge how critical a particular stretch of DNA is, biologists often look at the detailed sequence of "letters" it consists of, and compare it with a corresponding stretch in related creatures like mice. If the stretch serves no purpose, the thinking goes, the two sequences will differ because of numerous mutations since the two species last shared an ancestor. In contrast, it's believed that the sequences of important genes will be similar, or "conserved," in different species, because animals with mutations in these genes did not survive. Biologists therefore regard conserved sequences as a sign of biological importance. To test for conservation, researchers need to find matching stretches in the two species. This is relatively easy for stretches that "code" for proteins, where scientists long ago learned the meaning of the sequence. For "noncoding" regions, however, the comparison is often ambiguous. Even within a gene, stretches of DNA that code for pieces of the target protein are usually interspersed with much larger noncoding stretches, called introns, that are removed from the RNA working copy of the DNA before the protein is made. Signs of splicing Previous researchers assumed that mutations in the middle of introns do not affect the final protein, so they simply accumulate. In the new work, however, the researchers found signs that evolution rejects some types of mutations even in these regions of the genome. Although the selection is weak, "introns are not neutral," in their effect on survival, says CSHL professor Michael Zhang, a bioinformatics expert who headed the research team. To look for selection, CSHL researcher Chaolin Zhang, a doctoral candidate at Stony Brook University, looked in the human genome for a subtle statistical imbalance in how often various "letters" appear. The researchers attribute this imbalance to special short stretches of DNA that mark regions to be removed. Unless these signal sequences are sprinkled throughout an intron, the data suggest, it may not be properly spliced out, with potentially fatal consequences. Other sequences must likewise be preserved in the regions to be retained. The scientists found a preference for some "letters" across intron regions, and the opposite preference in coding regions. Together, these regions make up at least a third of the genome, which is thus under selective pressure during evolution. The result supports other recent studies that suggest that, although most DNA does not code for proteins, much of it is nonetheless biologically important. In addition to demonstrating how splicing affects genetic evolution, the statistical analysis identified possible signaling sequences, some that were already known and others that are new. According to co-author Adrian Krainer, a CSHL professor and splicing expert, "the exciting thing will be to experimentally test whether these predicted elements are really true." "RNA landscape of evolution for optimal exon and intron discrimination" appears in the April 15, 2008 edition of the Proceedings of the National Academy of Sciences. The complete citation is as follows: Chaolin Zhang, Wen-Hsiung Li, Adrian R. Krainer, and Michael Q. Zhang. The paper is available online at: http://www.pnas.org_cgi_doi_10.1073_pnas.0801692105 Cold Spring Harbor Laboratory is a private, non-profit research and education institution dedicated to exploring molecular biology and genetics in order to advance the understanding and ability to diagnose and treat cancers, neurological diseases and other causes of human suffering. For more information, visit http://www.cshl.edu Cold Spring Harbor Laboratory |
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| Related Human Genome Current Events and Human Genome News Articles Genetic analysis helps dissect molecular basis of cardiovascular disease Using highly precise measurements of plasma lipoprotein concentrations determined by nuclear magnetic resonance spectroscopy (NMR), researchers led by Daniel Chasman at Brigham and Women's Hospital and Harvard Medical School in Boston, MA, the Framingham Heart Study in Framingham, and the PROCARDIS consortium in Stockholm, Sweden and Oxford, England performed genetic association analysis across the whole genome among 17,296 women of European ancestry from the Women's Genome Health Study. New Maize Map to Aid Plant Breeding Efforts In a massive survey of genetic diversity in maize, also known as corn, researchers across the United States, have developed a gene map that should pave the way to significant improvements in a plant that is a major source of food, fuel, animal feed and fiber around the world. Largest gene study of childhood IBD identifies 5 new genes In the largest, most comprehensive genetic analysis of childhood-onset inflammatory bowel disease (IBD), an international research team has identified five new gene regions, including one involved in a biological pathway that helps drive the painful inflammation of the digestive tract that characterizes the disease. No-entry zones for AIDS virus The AIDS virus inserts its genetic material into the genome of the infected cell. Scientists of the German Cancer Research Center have now shown for the first time that the virus almost entirely spares particular sites in the human genetic material in this process. This finding may be useful for developing new, specific AIDS drugs. Aileron collaborates study in Nature: Stapled peptides inhibit Notch1 transcription factor This research validates the potential for Stapled Peptides to modulate key intracellular biological targets, such as transcription factors, that have not been addressable with current small molecule or biologic drug modalities. UCSD discovery allows scientists for the first time to experimentally annotate genomes Over the last 20 years, the sequencing of the human genome, along with related organisms, has represented one of the largest scientific endeavors in the history of mankind. Study sheds light on evolution of human complexity 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. Hunting for the Prozac Gene Prozac works wonders for some depressed people, but not for others. In some cases, patients derive little benefit and at worst, it can lead to bizarre hallucinations and fits of rage. Will genomics help prevent the next pandemic? This week, the Public Library of Science, an open-access publisher, presents the "Genomics of Emerging Infectious Disease," a collection of essays, perspectives, and reviews that explores how genomics-with all its associated tools and techniques-can provide insights into our understanding of emerging infectious disease. UCR researchers develop genetic map for cowpea, accelerating development of new varieties Cowpea, a protein-rich legume crop, is immensely important in many parts of the world, particularly drought-prone regions of Africa and Asia, where it plays a central role in the diet and economy of hundreds of millions of people. More Human Genome Current Events and Human Genome News Articles |
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