Refining the use of linkage disequilibrium as a robust signature of selective sweeps

Abstract

During a selective sweep, characteristic patterns of linkage disequilibrium can arise in the genomic region surrounding a selected locus. These have been used to infer past selective sweeps. However, the recombination rate is known to vary substantially along the genome for many species. We here investigate the effectiveness of current (Kelly's Z_nS and ω_max) and novel statistics at inferring hard selective sweeps based on linkage disequilibrium distortions under different conditions, including a human-realistic demographic model and recombination rate variation. When the recombination rate is constant, Kelly's Z_nS offers high power, but is outperformed by a novel statistic that we test, which we call Z_α. We also find this statistic to be effective at detecting sweeps from standing variation. When recombination rate fluctuations are included, there is a considerable reduction in power for all linkage disequilibrium-based statistics. However, this can largely be reversed by appropriately controlling for expected linkage disequilibrium using a genetic map. To further test these different methods, we perform selection scans on well-characterized HapMap data, finding that all three statistics—ω_max; Kelly’s Z_nS; and Z_α—are able to replicate signals at regions previously identified as selection candidates based on population differentiation or the site frequency spectrum. While ω_max replicates most candidates when recombination map data are not available, the Z_nS and Z_α statistics are more successful when recombination rate variation is controlled for. Given both this and their higher power in simulations of selective sweeps, these statistics are preferred when information on local recombination rate variation is available.

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