Detection of selective sweeps in cattle using genome-wide SNP data

Ramey et al. BMC Genomics 2013, 14:382 http://www.biomedcentral.com/1471-2164/14/382 RESEARCH ARTICLE Open Access Detection of selective sweeps in cattle using genome-wide SNP data Holly R Ramey1, Jared E Decker1, Stephanie D McKay1,2, Megan M Rolf1,3, Robert D Schnabel1 and Jeremy F Taylor1,4* Abstract Background: The domestication and subsequent selection by humans to create breeds and biological types of cattle undoubtedly altered the patterning of variation within their genomes. Strong selection to fix advantageous large-effect mutations underlying domesticability, breed characteristics or productivity created selective sweeps in which variation was lost in the chromosomal region flanking the selected allele. Selective sweeps have now been identified in the genomes of many animal species including humans, dogs, horses, and chickens. Here, we attempt to identify and characterise regions of the bovine genome that have been subjected to selective sweeps. Results: Two datasets were used for the discovery and validation of selective sweeps via the fixation of alleles at a series of contiguous SNP loci. BovineSNP50 data were used to identify 28 putative sweep regions among 14 diverse cattle breeds. Affymetrix BOS 1 prescreening assay data for five breeds were used to identify 85 regions and validate 5 regions identified using the BovineSNP50 data. Many genes are located within these regions and the lack of sequence data for the analysed breeds precludes the nomination of selected genes or variants and limits the prediction of the selected phenotypes. However, phenotypes that we predict to have historically been under strong selection include horned-polled, coat colour, stature, ear morphology, and behaviour. Conclusions: The bias towards common SNPs in the design of the BovineSNP50 assay led to the identification of recent selective sweeps associated with breed formation and common to only a small number of breeds rather than ancient events associated with domestication which could potentially be common to all European taurines. The limited SNP density, or marker resolution, of the BovineSNP50 assay significantly impacted the rate of false discovery of selective sweeps, however, we found sweeps in common between breeds which were confirmed using an ultra-high-density assay scored in a small number of animals from a subset of the breeds. No sweep regions were shared between indicine and taurine breeds reflecting their divergent selection histories and the very different environmental habitats to which these sub-species have adapted. Keywords: Selective sweep, Reduced heterozygosity, Signatures of selection, Single nucleotide polymorphisms Background The transition from hunter-gather lifestyles to permanent dwelling societies was facilitated by both plant and animal domestication [1]. The domestication of cattle occurred between 8,000 and 10,000 years ago and led to changes in the genome of the species due to the effects of demography and selection [2,3]. Much of the variation * Correspondence: 1 Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA 4 S135B Animal Sciences, University of Missouri, 920 East Campus Drive, Columbia, MO 65211-5300, USA Full list of author information is available at the end of the article within the genetically diverse ancestral population was either lost due to the limited sampling of animals within the sites of domestication or was partitioned into the subpopulations which went on to become recognised as distinct breeds. Selection for the phenotypes contributing to domesticability, biological type (draught, milk, meat) and the aesthetically appealing morphologies that have become breed hallmarks (polled, coat colour and patterning [4-8]) have also impacted the extent and distribution of variability within the genome. Strong on-going selection for variants of large effect leads to a loss of variation within the chromosomal region flanking the selected variant and ultimately the © 2013 Ramey et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Ramey et al. BMC Genomics 2013, 14:382 http://www.biomedcentral.com/1471-2164/14/382 complete fixation of the haplotype which harbours the variant. This phenomenon is known as the “hitch-hiking effect” [9] and a region of the genome in which artificial selection has driven a haplotype to complete fixation is defined as having been subjected to a “selective sweep”. Such regions may also occur within the genome due to random drift and these regions are not distinguishable from regions subjected to selective sweeps. Selective sweep studies differ from the classical “forward” genetics approach, which progresses from a phenotype to the identification of underlying causal genes and mutations. Rather, they follow a “reverse” genetics approach that begins with a signature of selection and attempts to infer the selected mutation and its associated phenotype [1]. An important reason for seeking selective sweeps is that these regions can elucidate the identities of genes and mutations with large phenotypic effect even if they are no longer segregating within any one population and thus cannot be detected by forward genetics without the formation of expensive crosses. Several methods have been used to identify regions of the genome which have been subjected to selective sweeps, including those based on modeling allele frequency spectra, linkage disequilibrium and haplotype structure [10-12]. These approaches require the use of high-density single nucleotide polymorphism (SNP) data which have previously been shown to be useful for detecting selective sweeps in human populations [13,14]. Studies aimed at localizing signatures of selection and selective sweeps have been performed in many animal species using SNP and microsatellite loci. These studies have pointed to interesting phenotypes which are important to understanding the nature of historic natural and artificial selection applied to these species. In chicken, selective sweeps have been found to involve loci believed to be inherent to domestication and include BCDO2 which controls yellow and white skin colours, SEMA3A which plays a role in axonal path-finding important in brain development, and THSR which is postulated to derestrict the regulation of seasonal reproduction [15]. Selective sweeps have been found in the dog genome at TRYP1 which controls black coat colour in Large Munsterlanders and at FGFR3 in Dachshunds [16]. FGFR3 mutations cause achondroplasia in humans and cattle. Other studies in dogs have identified a sweep surrounding IGF1 which is responsible for size variation [17] and in a genomic region for which the selected phenotype is unknown in Boxers [18]. Thes (...truncated)