Natural selection at linked sites in humans

Gene. 2002 Oct 30;300(1-2):31-42. doi: 10.1016/s0378-1119(02)00849-1.


Theoretical and empirical work indicates that patterns of neutral polymorphism can be affected by linked, selected mutations. Under background selection, deleterious mutations removed from a population by purifying selection cause a reduction in linked neutral diversity. Under genetic hitchhiking, the rise in frequency and fixation of beneficial mutations also reduces the level of linked neutral polymorphism. Here we review the evidence that levels of neutral polymorphism in humans are affected by selection at linked sites. We then discuss four approaches for distinguishing between background selection and genetic hitchhiking based on (i) the relationship between polymorphism level and recombination rate for neutral loci with high mutation rates, (ii) relative levels of variation on the X chromosome and the autosomes, (iii) the frequency distribution of neutral polymorphisms, and (iv) population-specific patterns of genetic variation. Although the evidence for selection at linked sites in humans is clear, current methods and data do not allow us to clearly assess the relative importance of background selection and genetic hitchhiking in humans. These results contrast with those obtained for Drosophila, where the signals of positive selection are stronger.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Africa
  • Europe
  • Gene Frequency
  • Genetic Linkage
  • Genetics, Population
  • Genome, Human
  • Humans
  • Mutation
  • Polymorphism, Genetic / genetics*
  • Recombination, Genetic / genetics
  • Selection, Genetic*