Detecting recent positive selection in the human genome from haplotype structure

Nature. 2002 Oct 24;419(6909):832-7. doi: 10.1038/nature01140. Epub 2002 Oct 9.


The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess the age of each core haplotype by the decay of its association to alleles at various distances from the locus, as measured by extended haplotype homozygosity (EHH). Core haplotypes that have unusually high EHH and a high population frequency indicate the presence of a mutation that rose to prominence in the human gene pool faster than expected under neutral evolution. We applied this approach to investigate selection at two genes carrying common variants implicated in resistance to malaria: G6PD and CD40 ligand. At both loci, the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection. More generally, the method could be used to scan the entire genome for evidence of recent positive selection.

Publication types

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

MeSH terms

  • Africa
  • Alleles
  • Animals
  • CD40 Ligand / genetics
  • Computer Simulation
  • Evolution, Molecular
  • Gene Pool
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation / genetics
  • Genome, Human*
  • Glucosephosphate Dehydrogenase / genetics
  • Haplotypes / genetics*
  • Homozygote
  • Humans
  • Malaria / enzymology
  • Malaria / genetics*
  • Malaria / parasitology
  • Male
  • Mutation / genetics
  • Plasmodium falciparum / physiology
  • Polymorphism, Single Nucleotide / genetics
  • Selection, Genetic*
  • Time Factors


  • CD40 Ligand
  • Glucosephosphate Dehydrogenase