Pervasive hitchhiking at coding and regulatory sites in humans.

PLoS Genetics
James J CaiDmitri A Petrov

Abstract

Much effort and interest have focused on assessing the importance of natural selection, particularly positive natural selection, in shaping the human genome. Although scans for positive selection have identified candidate loci that may be associated with positive selection in humans, such scans do not indicate whether adaptation is frequent in general in humans. Studies based on the reasoning of the MacDonald-Kreitman test, which, in principle, can be used to evaluate the extent of positive selection, suggested that adaptation is detectable in the human genome but that it is less common than in Drosophila or Escherichia coli. Both positive and purifying natural selection at functional sites should affect levels and patterns of polymorphism at linked nonfunctional sites. Here, we search for these effects by analyzing patterns of neutral polymorphism in humans in relation to the rates of recombination, functional density, and functional divergence with chimpanzees. We find that the levels of neutral polymorphism are lower in the regions of lower recombination and in the regions of higher functional density or divergence. These correlations persist after controlling for the variation in GC content, density of simple repeats, selec...Continue Reading

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Methods Mentioned

BETA
chip

Software Mentioned

Matlab
CODEML
PAML
MBEToolbox
Ensembl compara
Ensembl
PGEToolbox
CLUSTALW
UCSC genome browser
RepeatMasker

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