Genome-wide inference of natural selection on human transcription factor binding sites

26/02/2013 - Room C209 at 14:00 - External Seminar
Adam Siepel
(EMBl-EBI )
For decades, it has been hypothesized that gene regulation has played a central role in human evolution, yet much remains unknown about the genome-wide impact of regulatory mutations. Here we use complete genome sequences and genome-wide chromatin immuno-precipitation and sequencing data to demonstrate that natural selection has exerted a profound influence on human transcription factor binding sites since our divergence from chimpanzees 4-6 million years ago. Our analysis is based on a new probabilistic method for characterizing natural selection from collections of short interspersed noncoding elements. We find that binding sites have experienced somewhat weaker selection than protein-coding genes, on average, but that the binding sites of several transcription factors show clear evidence of adaptation. We project that regulatory elements may make larger cumulative contributions than protein-coding genes to both adaptive substitutions and deleterious polymorphisms, which has important implications for human evolution and disease. Adam Siepel is currently spending a sabbatical year at EBI, and is happy to hear from people who'd like to meet with him. Anyone who would like to talk to Adam in the afternoon following his talk should contact Zoe Higney <zhigney@ebi.ac.uk> to arrange an appointment.
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