Chapter 10: Umbrella reviews

Abstract

The search for functional regions in the human genome, beyond the protein-coding portion, often relies on signals of conservation across species. The Human Accelerated Regions (HARs) are strongly conserved elements, ranging in size from 100–400 bp, that show an unexpected number of human-specific changes. This pattern suggests that HARs may be functional elements that have significantly changed during human evolution. To analyze the evolutionary forces that led these changes, we studied 40 kb neighborhoods of the top 49 HARs. We took advantage of recently developed DNA sequencing technology, coupled with methods to isolate genomic DNA for our target regions only, to determine the genotypes in 22 chromosomal samples. This polymorphism data showed no significant evidence for adaptive selective sweeps in HAR regions. By contrast, we found strong evidence for a nucleotide bias in the fixation of mutations from A or T to G or C basepairs. Our work reveals that this bias in the HAR neighborhoods is not just an historic phenomenon, but is ongoing in the present day human population. This finding adds credence to the possibility that non-selective forces, such as biased gene conversion, could have contributed to the evolution of several of these regions.