Classic Selective Sweeps Revealed by Massive Sequencing in Cattle

Abstract

Author Summary Domestication of cattle had a major impact on human civilization by providing protein and physical power for agrarian life style. Domestication followed by breed formation has likely left detectable signatures within the genome of modern cattle. Current cattle breeds, for instance, have a more uniform appearance and milder temper than their wild ancestors. The elucidation of these signatures of selection is of interest to identify domestication-related genes that help to genetically improve this economically important species. The development of novel sequencing technologies has enabled higher-resolution genomic analyses of past selection. In this paper, we exploited whole genome sequencing along with multiple statistical metrics to identify regions/genes putatively targeted by selection. We show strong signals of selection near to several candidate genes related to domesticated phenotypes such as coat coloring, neurobehavioral functioning and sensory perception, including KIT, MITF, MC1R, NRG4, Erbb4, TMEM132D and TAS2R16. By means of association mapping we additionally show that candidate selection regions for appearance traits overlap with major coat color QTLs. Our study demonstrates the utility of population based techniques for detecting past selection and is the first attempt to localize signatures of past selection in cattle based on massive re-sequencing of the entire genome. Human driven selection during domestication and subsequent breed formation has likely left detectable signatures within the genome of modern cattle. The elucidation of these signatures of selection is of interest from the perspective of evolutionary biology, and for identifying domestication-related genes that ultimately may help to further genetically improve this economically important animal. To this end, we employed a panel of more than 15 million autosomal SNPs identified from re-sequencing of 43 Fleckvieh animals. We mainly applied two somewhat complementary statistics, the integrated Haplotype Homozygosity Score (iHS) reflecting primarily ongoing selection, and the Composite of Likelihood Ratio (CLR) having the most power to detect completed selection after fixation of the advantageous allele. We find 106 candidate selection regions, many of which are harboring genes related to phenotypes relevant in domestication, such as coat coloring pattern, neurobehavioral functioning and sensory perception including KIT, MITF, MC1R, NRG4, Erbb4, TMEM132D and TAS2R16, among others. To further investigate the relationship between genes with signatures of selection and genes identified in QTL mapping studies, we use a sample of 3062 animals to perform four genome-wide association analyses using appearance traits, body size and somatic cell count. We show that regions associated with coat coloring significantly (P<0.0001) overlap with the candidate selection regions, suggesting that the selection signals we identify are associated with traits known to be affected by selection during domestication. Results also provide further evidence regarding the complexity of the genetics underlying coat coloring in cattle. This study illustrates the potential of population genetic approaches for identifying genomic regions affecting domestication-related phenotypes and further helps to identify specific regions targeted by selection during speciation, domestication and breed formation of cattle. We also show that Linkage Disequilibrium (LD) decays in cattle at a much faster rate than previously thought.