Using the variability of linkage disequilibrium between subpopulations to infer sweeps and epistatic selection in a diverse panel of chickens

Abstract

A whole-genome scan for identifying selection acting on pairs of linked loci is proposed and implemented. The scan is based on , one of Ohta's 1982 measures of between-population linkage disequilibrium (LD). An approximate empirical null distribution for the statistic is suggested. Although the partitioning of LD into between-population components was originally used to investigate epistatic selection, we demonstrate that values of may also be influenced by single-locus selective sweeps with linkage but no epistasis. The proposed scan is implemented in a diverse panel of chickens including 72 distinct breeds genotyped at 538 298 single-nucleotide polymorphisms. In all, 1723 locus pairs are identified as putatively corresponding to a selective sweep or epistatic selection. These pairs of loci generally cluster to form overlapping or neighboring signals of selection. Known variants that were expected to have been under selection in the panel are identified, as well as an assortment of novel regions that have putatively been under selection in chickens. Notably, a promising pair of genes located 8 MB apart on chromosome 9 are identified based on as demonstrating strong evidence of dispersive epistatic selection between populations.

Figure 1

Null vs experimental distributions. Histograms comparing the null and experimental distribution for . Observe that the distributions are quite similar, but the experimental distribution is slightly inflated.

Figure 2

Location of significant locus pairs. A whole-genome map of loci where significant values of were identified in the chicken genome. The position of every marker that was part of a significant pair is represented. Positions are plotted according to the galGal4 assembly. These loci are those putatively under dispersive selective sweeps or dispersive cis-acting epistatic selection.

Figure 3

The BCDO2 locus. Depiction of significant locus pairs identified in the BCDO2 region of chromosome 24, and the value observed for each significant pair. The height of each dashed line depicts the value of observed for that pair.

Figure 4

Sweeps vs potential epistatic selection. values for two example regions. a and b demonstrate region on chromosome 5 showing patterns consistent with a large selective sweep. c and d are of a region on chromosome 6, where significance was not clear except for specific locus pairs, suggestive of epistasis. (a) Significant locus pairs identified across a region of chromosome 5; (b) for every locus pair across the same region of chromosome 5. Values are plotted at the midpoint of the locus pair. Significant pairs are highlighted in red; (c) Significant locus pairs identified across a region of chromosome 6; (d) for every locus pair across the same region of chromosome 6.