A Genome Scan for Positive Selection in Thoroughbred Horses

Abstract

Thoroughbred horses have been selected for exceptional racing performance resulting in system-wide structural and functional adaptations contributing to elite athletic phenotypes. Because selection has been recent and intense in a closed population that stems from a small number of founder animals Thoroughbreds represent a unique population within which to identify genomic contributions to exercise-related traits. Employing a population genetics-based hitchhiking mapping approach we performed a genome scan using 394 autosomal and X chromosome microsatellite loci and identified positively selected loci in the extreme tail-ends of the empirical distributions for (1) deviations from expected heterozygosity (Ewens-Watterson test) in Thoroughbred (n = 112) and (2) global differentiation among four geographically diverse horse populations (FST). We found positively selected genomic regions in Thoroughbred enriched for phosphoinositide-mediated signalling (3.2-fold enrichment; P<0.01), insulin receptor signalling (5.0-fold enrichment; P<0.01) and lipid transport (2.2-fold enrichment; P<0.05) genes. We found a significant overrepresentation of sarcoglycan complex (11.1-fold enrichment; P<0.05) and focal adhesion pathway (1.9-fold enrichment; P<0.01) genes highlighting the role for muscle strength and integrity in the Thoroughbred athletic phenotype. We report for the first time candidate athletic-performance genes within regions targeted by selection in Thoroughbred horses that are principally responsible for fatty acid oxidation, increased insulin sensitivity and muscle strength: ACSS1 (acyl-CoA synthetase short-chain family member 1), ACTA1 (actin, alpha 1, skeletal muscle), ACTN2 (actinin, alpha 2), ADHFE1 (alcohol dehydrogenase, iron containing, 1), MTFR1 (mitochondrial fission regulator 1), PDK4 (pyruvate dehydrogenase kinase, isozyme 4) and TNC (tenascin C). Understanding the genetic basis for exercise adaptation will be crucial for the identification of genes within the complex molecular networks underlying obesity and its consequential pathologies, such as type 2 diabetes. Therefore, we propose Thoroughbred as a novel in vivo large animal model for understanding molecular protection against metabolic disease.

A Genome-Wide Scan for Evidence of Selection in a Maize Population Under Long-Term Artificial Selection for Ear Number

“…In maize, the expression of the tb1 gene has been shown to be affected by intergenic sequence tens of kilobases away from the gene itself (Clark et al, 2006). Similarly, the finding appears to be pervasive in domesticated animal species, where studies involving horses (Gu et al, 2009), cattle (Qanbari et al 2011), and chickens (Qanbari et al 2012) have all identified selection in genepoor regions. Likewise, in human populations it has been observed that at a minimum, 14% of selected regions identified across multiple studies result from selection on noncoding material (Akey 2009).…”

Brief Review of Equine Genomics: Prospects toward Exercise and Sports Science

“…According to the author, his main physiological pathways related to these genes were fatty acid metabolism, oxidative phosphorylation and actin cytoskeleton. 32 Further population-based studies of selection in horses using microsatellites and Di statistic (designed to detect significance that are near or at fixation within a population) supported the use of these techniques to identify novel variants and selection induced changes in equine genome. 33 The comparison of three different breeds (THB, QH and Paint Horse -PH) was carried out in order to identify regions of putative selection in horses engaged in different optimal race distance.…”

“…The opposite extreme (positive end) shows the effect of balancing selection. 32 In order to identify genomic regions targeted for positive selection in Thoroughbred horses, several breeds were compared using FST and H0 approaches. Clusters of outlier loci with high values of FST (>0.25) and low H0 were observed only in Thoroughbreds, which reveal evidence of population differentiation.…”

“…43 The very high muscle mass to body weight ratio observed in horses (55%), compared to other species, 3 is probably a trait targeted for artificial selection, especially in Thoroughbred horses. 32 Considering the important contribution of muscle power to flat race ability, the association between MSTN sequence variant and racing performance was investigated in a series of population-basis case control study by separating thoroughbreds (n=148) on the basis of retrospective racecourse performance. Genotypes of two single nucleotides polymorphisms attempted (g.6649373737C>T and g.66494218A>C) were not more common among winning thoroughbreds than nonwinning thoroughbred horses, however the comparison of horses winning short race (<8 furlongs) with horses winning long distance race (>8 f) revealed significant association.…”

Candidate genes for performance in horses, including monocarboxylate transporters

“…Two candidate genes, PDK4 and DMRT3, have been studied for athletic potential as possible markers for performance in horses. The expression of the pyruvate dehydrogenase kinase, isozyme 4 -PDK4 (Gu et al 2009, Hill et al 2010, located on equine chromosome 4 (ECA4) helps to control metabolism and glucose conversion to acetyl-CoA for production of ATP (Andrews et al 1998). This regulation of glucose conversion is tightly controlled by conversion of pyruvate to acetyl-CoA in the mitochondrion by catalytic function of the pyruvate dehydrogenase complex (PDC), which is controlled by pyruvate dehydrogenase kinase (PDK).…”