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. 2009 Jun 2;4(6):e5767.
doi: 10.1371/journal.pone.0005767.

A genome scan for positive selection in thoroughbred horses

Jingjing Gu  1 , Nick Orr, Stephen D Park, Lisa M Katz, Galina Sulimova, David E MacHugh, Emmeline W Hill
Affiliations

A genome scan for positive selection in thoroughbred horses

Jingjing Gu et al. PLoS One. .

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 (F(ST)). 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Empirical distribution for Dh/sd.
The empirical distribution for Dh/sd scores (horizontal axis) from the Ewens-Watterson test. The vertical axis indicates the number of loci with the corresponding Dh/sd score. The positions in the distribution of the regions that have been subject to selection in Thoroughbred are indicated by the gene symbols for the strongest candidate genes. Genes in the negative tail-end of the distribution may have been subject to positive selection. Genes in the positive end of the distribution may have been subject to balancing selection.
Figure 2
Figure 2. F ST versus heterozygosity.
F ST (vertical axis) versus heterozygosity (horizontal axis) plots for Thoroughbred, Akhal-Teke, Connemara and Tuva at 394 genome-wide microsatellite loci.
Figure 3
Figure 3. Chromosome-wide F ST versus Thoroughbred heterozygosity.
F ST (solid line) versus Thoroughbred heterozygosity (dashed line) plots across chromosomes for the nine highest F ST regions with significant (P<0.05) deviations from expected heterozygosity (Dh/sd) in Thoroughbred. Loci defining selected genomic regions are highlighted. Left vertical axis: F ST; Right vertical axis: Thoroughbred heterozygosity; Horizontal axis: chromosome position (Mb).
Figure 4
Figure 4. Empirical distribution for F ST.
The empirical distribution for global differentiation, F ST (horizontal axis). The vertical axis indicates the number of loci with the corresponding F ST. The positions of the regions that have been subject to positive selection in Thoroughbred are located in the tail-end of the distribution and are indicated by the gene symbols for the strongest candidate genes.
See this image and copyright information in PMC

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