title: Forces shaping the fastest evolving regions in the human genome.
abstract: Comparative genomics allow us to search the human genome for segments that were extensively changed in the last approximately 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 directional selection in the regions containing the two most accelerated regions. A combination of evolutionary forces has contributed to accelerated evolution of the fastest evolving elements in the human genome.
authors.affiliation: Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America. kspollard@ucdavis.edu
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Pollard
authors.forename: Sofie R
authors.initials: SR
authors.lastname: Salama
authors.forename: Bryan
authors.initials: B
authors.lastname: King
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Kern
authors.forename: Tim
authors.initials: T
authors.lastname: Dreszer
authors.forename: Sol
authors.initials: S
authors.lastname: Katzman
authors.forename: Adam
authors.initials: A
authors.lastname: Siepel
authors.forename: Jakob S
authors.initials: JS
authors.lastname: Pedersen
authors.forename: Gill
authors.initials: G
authors.lastname: Bejerano
authors.forename: Robert
authors.initials: R
authors.lastname: Baertsch
authors.forename: Kate R
authors.initials: KR
authors.lastname: Rosenbloom
authors.forename: Jim
authors.initials: J
authors.lastname: Kent
authors.forename: David
authors.initials: D
authors.lastname: Haussler
mesh_terms: D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D017124:Conserved Sequence; D019143:Evolution, Molecular; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013045:Species Specificity