Accounting for linkage disequilibrium in genome scans for selection without individual genotypes: The local score approach

Abstract

Detecting genomic footprints of selection is an important step in the understanding of evolution. Accounting for linkage disequilibrium in genome scans increases detection power, but haplotype-based methods require individual genotypes and are not applicable on pool-sequenced samples. We propose to take advantage of the local score approach to account for linkage disequilibrium in genome scans for selection, cumulating (possibly small) signals from single markers over a genomic segment, to clearly pinpoint a selection signal. Using computer simulations, we demonstrate that this approach detects selection with higher power than several state-of-the-art single-marker, windowing or haplotype-based approaches. We illustrate this on two benchmark data sets including individual genotypes, for which we obtain similar results with the local score and one haplotype-based approach. Finally, we apply the local score approach to Pool-Seq data obtained from a divergent selection experiment on behaviour in quail and obtain precise and biologically coherent selection signals: while competing methods fail to highlight any clear selection signature, our method detects several regions involving genes known to act on social responsiveness or autistic traits. Although we focus here on the detection of positive selection from multiple population data, the local score approach is general and can be applied to other genome scans for selection or other genomewide analyses such as GWAS.

A guinea fowl genome assembly provides new evidence on evolution following domestication and selection in galliformes

“…TMLHE is the first enzyme in the carnitine biosynthesis pathway, and TMLHE deficiency causes regressive autism symptoms that can be improved via carnitine supplementation (Ziats et al., ). It is worth noting also that a region containing a gene involved in autism in human was detected when comparing two lines of quail divergently selected on social behaviour (Fariello et al., ). Severe mutations in TMLHE cause extreme phenotypes, such as seen in human and model organisms, and it would not be surprising that a polymorphism in such a gene causing milder phenotypes could reside in regulatory region situated for instance in the promoter or in introns.…”

“…Genomic regions showing an excess of genetic differentiation between populations, compared to what is expected under neutral evolution, were detected using the local score approach of Fariello et al. (). This approach proceeds in two steps.…”

“…Following Fariello et al. (), we computed single marker p ‐values using the FLK test (Bonhomme et al., ), implemented in the hapflk software, https://forge-dga.jouy.inra.fr/projects/hapflk. The FLK statistic is an extension of the classical FST statistic that accounts for differences of effective population size among populations, and for the hierarchical structure of populations.…”

“…Fariello et al. () indicated that this choice was in principle preferable to ε = 1 for the detection of old selection events, as this gives more weight to short segments with high p ‐values, compared to long segments with moderate p ‐values. In their simulations, selection started 20 or 40 generations ago, which is younger than what we targeted here when studying the effects of domestication or importation to Europe.…”

“…Selective sweeps within each population were detected using the pred option of pool-hmm. This command implements the Hidden Markov Model (HMM) approach originally proposed by Boitard, Schlotterer, and Futschik (2009) Following Fariello et al (2017), we computed single marker pvalues using the FLK test (Bonhomme et al, 2010), implemented in the hapflk software, https ://forge-dga.jouy.inra.fr/proje cts/hapflk. The FLK statistic is an extension of the classical FST statistic that accounts for differences of effective population size amo ng populations, and for the hiera rchical structure of populations .…”