forces shaping the fastest evolving regions in the human genome力量塑造在人类基因组中发展最快的地区.pdfVIP

Forces Shaping the Fastest Evolving Regions in the Human Genome 1¤a* 1,2 1,2 1 1 1,2 Katherine S. Pollard , Sofie R. Salama , Bryan King , Andrew D. Kern , Tim Dreszer , Sol Katzman , 1¤b 1 1 1 1 1 Adam Siepel , Jakob S. Pedersen , Gill Bejerano , Robert Baertsch , Kate R. Rosenbloom , Jim Kent , David Haussler1,2 1 Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America, 2 Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, California, United States of America Comparative genomics allow us to search the human genome for segments that were extensively changed in the last ;5 million years since divergence from our common ancestor with chimpanzee, but are highly conserved in other species and thus are likely to be functional. We found 202 genomic elements that are highly conserved in vertebrates but show evidence of significantly accelerated substitution rates in human. These are mostly in non-coding DNA, often near genes associated with transcription and DNA binding. Resequencing confirmed that the five most accelerated elements are dramatically changed in human but not in other primates, with seven times more substitutions in human than in chimp. The accelerated elements, and in particular the top five, show a strong bias for adenine and thymine to guanine and cytosine nucleotide changes and are disproportionately located in high recombination and high guanine and cytosine content environments near telomeres, suggesting either biased gene conversion or isochore selection. In addition, there is some evidence of d