The origin of the double-muscle mutation in the MSTN gene of sheep and its effects on growth traits in the Hu × East Friesian hybrid population

Introduction The g.119292288G A mutation in the 3′ untranslated region (3′UTR) of the myostatin ( MSTN ) gene is a well-known functional variant associated with increased muscling in Texel sheep. However, its evolutionary origin and historical dynamics remain unresolved, which are critical for understanding the genomic architecture of major-effect mutations and their implications for animal breeding. Methods We analyzed whole-genome sequencing data from 73 diverse global sheep breeds to characterize the allele frequency distribution of the MSTN g.119292288GA mutation. Selection history was inferred using ancestral recombination graph–based approaches implemented in Relate and CLUES. To assess the temporal origin of the mutation, we screened 31 ancient European sheep genomes dated between 8,200 and 440 years before present. The phenotypic effects of the mutation were evaluated using association analyses in a Hu × East Friesian hybrid population. Results The derived allele (A) showed a high frequency (0.7) in East Friesian, Texel, and Dairy Meade sheep, but was rare or absent in other breeds, suggesting a likely origin in the northern Netherlands, particularly in the regions of Texel Island and Friesland Province. Selection analyses indicated that this allele experienced strong positive selection within the last ~300 years. Notably, neither the mutation nor its associated haplotype was detected in any of the ancient European samples, supporting a relatively recent emergence. In the Hu × East Friesian hybrid population, individuals carrying the mutant allele exhibited significantly greater birth weight, weaning weight, and six-month body weight compared to wild-type homozygotes ( p 0.05). Conclusion Together, our results provide a comprehensive overview of the origin, spread, and phenotypic impact of the MSTN g.119292288G A mutation, offering valuable insights for identifying and utilizing major-effect mutations in genomic breeding programs.