Forces shaping the fastest evolving regions in the human genome.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Pollard, Katherine S; Salama, Sofie R; King, Bryan; Kern, Andrew D; Dreszer, Tim; Katzman, Sol; Siepel, Adam; Pedersen, Jakob S; Bejerano, Gill; Baertsch, Robert; Rosenbloom, Kate R; Kent, Jim; Haussler, David
Year of Publication: 2006
Journal: PLoS Genet
Volume: 2
Issue: 10
Pagination: e168
Date Published: 10/2006
Publication Language: eng
ISSN: 1553-7404
Keywords: Animals, Base Pairing, Base Sequence, Conserved Sequence, Evolution, Molecular, Genome, Human, Humans, Molecular Sequence Data, Recombination, Genetic, Regulatory Elements, Transcriptional, Selection, Genetic, Sequence Analysis, DNA, Species Specificity

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.

DOI: 10.1371/journal.pgen.0020168
Alternate Journal: PLoS Genet.