Genome-wide analysis reveals selection for important traits in domestic horse breeds.

Jessica L Petersen ,Sofia Mikko,Tosso Leeb,Artur Da Câmara Machado,Claire M Wade,E Gus Cothran,June Swinburne,Gabriella Lindgren,Gérard Guérin,Bianca Haase,Karin Hemmann,Richard J Piercy,Hannes Lohi,James R Mickelson,Nicholas Orr,Telhisa Hasegawa,Katia Cappelli,Marja Raekallio,Beatrice A Mcgivney,Teruaki Tozaki,Stephanie J Valberg,Stefan Rieder,Molly E Mccue,Stefano Capomaccio,Alexandre Secorun Borges ,Mark D Vaudin ,Kathryn Graves ,M C T Penedo ,E Bailey ,J Axelsson ,Danika L Bannasch ,M S Lopes ,Knut Røed ,M M Binns ,O Distl ,Aaron Rendahl ,P A J Brama ,E W Hill ,Laura Y Fox-Clipsham ,Lisa Andersson

doi:10.1371/journal.pgen.1003211

Abstract

Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an FST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse.

Highlights

Since domestication of the horse approximately 5,000 years ago [1,2,3], selective breeding has been directed mainly toward the use of the horse in agriculture, transportation, and warfare
High-throughput, whole-genome single nucleotide polymorphism (SNP) arrays can be used to exploit this population structure to identify the effects of selection upon the equine genome
23,401 SNPs were evaluated within 3,229 windows (68.7% of the autosomes), averaging 7.25 SNPs per window

Summary

Introduction

Since domestication of the horse approximately 5,000 years ago [1,2,3], selective breeding has been directed mainly toward the use of the horse in agriculture, transportation, and warfare. Population-based approaches to identify signals of selection using loss of heterozygosity and/or other diversity indices have been successful in several domestic species. In dogs, these studies have led to the identification of genomic regions implicated in the selection of characteristics such as coat color and texture, body size, skin wrinkling, and disease [4,5], as well as the identification of signals of selection across genes with both known and unknown function [6,7,8,9]. While a considerable number of traits are under selection in the many breeds and performance groups of the horse, the only prior population-based study of selection in the horse utilized microsatellite loci to identify loci of importance to the Thoroughbred with respect to three other breeds [15]

Methods

Results

Discussion

Conclusion