Detecting recent selective sweeps while controlling for mutation rate and background selection

TY - JOUR

T1 - Detecting recent selective sweeps while controlling for mutation rate and background selection

AU - Huber, Christian D.

AU - DeGiorgio, Michael

AU - Hellmann, Ines

AU - Nielsen, Rasmus

PY - 2016

Y1 - 2016

N2 - A composite likelihood ratio test implemented in the program sweepfinder is a commonly used method for scanning a genome for recent selective sweeps. sweepfinder uses information on the spatial pattern (along the chromosome) of the site frequency spectrum around the selected locus. To avoid confounding effects of background selection and variation in the mutation process along the genome, the method is typically applied only to sites that are variable within species. However, the power to detect and localize selective sweeps can be greatly improved if invariable sites are also included in the analysis. In the spirit of a Hudson-Kreitman-Aguadé test, we suggest adding fixed differences relative to an out-group to account for variation in mutation rate, thereby facilitating more robust and powerful analyses. We also develop a method for including background selection, modelled as a local reduction in the effective population size. Using simulations, we show that these advances lead to a gain in power while maintaining robustness to mutation rate variation. Furthermore, the new method also provides more precise localization of the causative mutation than methods using the spatial pattern of segregating sites alone.

AB - A composite likelihood ratio test implemented in the program sweepfinder is a commonly used method for scanning a genome for recent selective sweeps. sweepfinder uses information on the spatial pattern (along the chromosome) of the site frequency spectrum around the selected locus. To avoid confounding effects of background selection and variation in the mutation process along the genome, the method is typically applied only to sites that are variable within species. However, the power to detect and localize selective sweeps can be greatly improved if invariable sites are also included in the analysis. In the spirit of a Hudson-Kreitman-Aguadé test, we suggest adding fixed differences relative to an out-group to account for variation in mutation rate, thereby facilitating more robust and powerful analyses. We also develop a method for including background selection, modelled as a local reduction in the effective population size. Using simulations, we show that these advances lead to a gain in power while maintaining robustness to mutation rate variation. Furthermore, the new method also provides more precise localization of the causative mutation than methods using the spatial pattern of segregating sites alone.

KW - background selection

KW - Hudson-Kreitman-Aguadé test

KW - population bottlenecks

KW - sweep detection

KW - sweepfinder

U2 - 10.1111/mec.13351

DO - 10.1111/mec.13351

M3 - Journal article

C2 - 26290347

AN - SCOPUS:84954078351

SN - 0962-1083

VL - 25

SP - 142

EP - 156

JO - Molecular Ecology

JF - Molecular Ecology

IS - 1

ER -