background selection
McVicker G, Gordon D, Davis C & Green P 2009 Widespread genomic signatures of natural selection in hominid evolution. PLoS Genet 5:e1000471.
- we analyzed the genomic distributions of human polymorphisms and sequence differences among five primate species relative to the locations of conserved sequence features
- neutral sequence diversity in human and ancestral hominid populations is substantially reduced near such features, resulting in a surprisingly large genome average diversity reduction due to selection of 19–26% on the autosomes and 12–40% on the X chromosome
- the overall trends are broadly consistent with "background selection" or hitchhiking in ancestral populations acting to remove deleterious variants
- average selection is much stronger on exonic (both protein-coding and untranslated) conserved features than non-exonic features
- long term selection, rather than complex speciation scenarios, explains the large intragenomic variation in human/chimpanzee divergence
- we attempted to discriminate between background selection and hitchhiking models by examining allele frequency distributions in regions near or far from conserved segments
- we were not able to find conclusive evidence that favored one model over the other
- both hitchhiking and background selection are likely to contribute to patterns of genomic diversity
- future work would ideally take both forces into account
- Cai et al. estimated hitchhiking or background selection has reduced neutral diversity by 6% genome-wide (11% in gene-rich regions)
- their estimate is substantially lower than our own (19–26% for autosomes)
- they exclude all sites near genes (within 5 kb of transcript start and ends and within 1 kb of any exon)
- since about 11% of the genome is within 1 kb of an exon this omits a large fraction of the sites that are the most influenced by selection
- their analysis uses very large windows (400 kb) which will tend to dilute some of the effects of selection
- they normalize human diversity by H/C divergence as a correction for mutation rate variaton
- this normalization is overly conservative because as we have shown here, a substantial fraction of H/C divergence is itself affected by selection
