soft sweep

Barreiro LB, Ben-Ali M, Quach H, Laval G, Patin E, Pickrell JK, Bouchier C, Tichit M, Neyrolles O, Gicquel B, Kidd JR, Kidd KK, Alcaïs A, Ragimbeau J, Pellegrini S, Abel L, Casanova JL & Quintana-Murci L 2009 Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense. PLoS Genet 5:e1000562.

  • to identify more precisely the allele(s)/haplotype(s) being targeted by selection, we developed a new statistic — the Derived Intra-allelic Nucleotide Diversity (DIND) test — that makes maximum profit of resequencing data
  • under neutral conditions, a derived allele that is at high population frequencies should present high levels of nucleotide diversity at linked sites
  • conversely, a derived allele that is positively selected will increase in frequency much quicker than the time needed to accumulate diversity at linked sites
  • derived allele targeted by positive selection will be at high population frequencies but associated with low nucleotide diversity at linked sites
  • we first evaluated the power of the DIND test with respect to other commonly used frequency- and LD-based neutrality tests (i.e., Tajimas's D, Fu and Li's F*, Fay and Wu's H and iHS)
  • the DIND test clearly outperformed the other tests, particularly when the selected allele is found at a population frequency <70%
  • the power of the test drops only when the selected allele is observed at near-fixation
  • the DIND test is especially useful for the identification of ongoing sweeps
  • Derived Intra-allelic Nucleotide Diversity (DIND) test
  • the commonly used sequence-based neutrality tests have low power to detect selection, particularly if the selective events are too recent
  • the DIND test is based on the ratio iπA / iπD plotted against the frequency of the derived allele
  • a high iπA / iπD ratio (i.e., iπA≪iπD) together with a high frequency of the derived allele points to the action of positive selection
  • i.e., the internal diversity of the haplotypes associated with the derived allele is too small given the frequency of this allele in the population