College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA.
PLoS Genet. 2013;9(1):e1003211. doi: 10.1371/journal.pgen.1003211. Epub 2013 Jan 17.
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 F(ST)-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.
短时间内的强烈选择压力导致马品种内部同质化，但品种间存在大量变异。利用这种群体结构，对 33 个品种的 744 个个体和一个 54,000 SNP 基因分型阵列进行了分析，通过在整个基因组中以 500-kb 窗口计算的基于 F(ST)的统计量，确定了品种特异性的选择靶标。ECA18 上的一个 5.5-Mb 区域，肌生成抑制素 (MSTN) 基因位于其中央，在油漆马和夸特马中都显示出最高的选择信号。臀肌活检的基因测序和组织学分析表明，MSTN 的启动子变体和内含子 SNP 都与夸特马中更高的 2B 型和更低的 1 型肌肉纤维比例显著相关，表明该基因座的选择具有功能后果。样本中所有步态品种 ECA23 上的选择信号导致鉴定出一个共享的 186-kb 单倍型，包括两个 doublesex 相关 mab 转录因子基因 (DMRT2 和 3)。最近在这个单倍型中发现了一个 DMRT3 突变，这似乎是表现替代步态的必要条件，为该基因座的选择提供了进一步的证据。最后，在 ECA11 上的草稿品种和微型马中确定了大小决定的假定基因座，以及在检查其他基因座候选基因周围的选择信号时。这项工作进一步证明了 MSTN 在赛马品种中的重要性，为步态和体型的选择提供了有力证据，并说明了基于群体的技术在发现现代马重要表型的基因组区域方面的潜力。
