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PloS one2018; 13(10); e0205664; doi: 10.1371/journal.pone.0205664

The “speed gene” effect of myostatin arises in Thoroughbred horses due to a promoter proximal SINE insertion.

Abstract: Thoroughbred horses are finely-tuned athletes with a high aerobic capacity relative to skeletal muscle mass, attributable to centuries of genetic selection for speed and stamina. Polymorphisms in the myostatin gene (MSTN), a pronounced inhibitor of skeletal muscle growth, have been shown to almost singularly account for gene-based race distance aptitude in racehorses. In Thoroughbreds, two MSTN polymorphisms, a single nucleotide variation in the first intron (SNP g.66493737C>T) and a non-coding transposable element within the promoter region (a 227 bp SINE insertion) are of particular interest. Until now, it has not been clear which of these variants affect skeletal muscle phenotypes or whether both can impact racing performance. In a large cohort of Thoroughbreds, we observed a complete concordance between the SNP and the SINE insertion. By means of in vitro assays in C2C12 myoblasts, we isolated the SNP variant from the SINE polymorphism and showed the latter is exclusively responsible for adversely affecting transcription initiation and gene expression thereby limiting myostatin protein production. Mapping the MSTN transcription start site in horse skeletal muscle likewise revealed anomalous transcription initiation in the presence of the SINE insertion. Our data provides mechanistic evidence that the SINE insertion uniquely accounts for the MSTN "speed gene" effect on race distance aptitude in the Thoroughbred horse.
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Publication Date: 2018-10-31 PubMed ID: 30379863PubMed Central: PMC6209199DOI: 10.1371/journal.pone.0205664Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigated a gene known as myostatin in Thoroughbred horses. The finding links a specific genetic variation (a SINE insertion) to decreased myostatin production, which determines a horse’s aptitude for certain race distances.

Genetic Background of Thoroughbred Horses

  • Thoroughbred horses, known for their speed and stamina, have been bred over centuries with these traits in mind.
  • The gene myostatin (MSTN) in these horses is a significant inhibitor of skeletal muscle growth.
  • Polymorphisms, or differences in this gene, are believed to account for a horse’s genetic predisposition towards specific race distances.

Two Polymorphisms of Interest

  • The first is a Single Nucleotide Polymorphism (SNP) variation in the first intron of the MSTN gene.
  • The second is a Short Interspersed Nuclear Element (SINE) insertion in the promoter region of the MSTN gene.
  • Prior to this research, it was unclear whether one or both of these variations influenced a horse’s racing performance or skeletal muscle development.

Concordance and In Vitro Testing

  • A complete match was found between the SNP and SINE insertion across a large sample of Thoroughbred horses.
  • The researchers conducted in vitro assays in C2C12 myoblasts (a type of precursor cell to muscle tissue) to separate the effects of SNP and SINE.
  • The SINE insertion was shown to be solely responsible for reducing MSTN’s ability to initiate transcription and produce myostatin protein, thereby impacting muscle growth.

Implications of the SINE Insertion

  • When the MSTN gene’s transcription start site was mapped in horse skeletal muscle, unusual transcription initiation was detected in horses with the SINE insertion.
  • This demonstrates that the presence of the SINE insertion, rather than the SNP, influences the production of myostatin and the resulting running capacity of the horse.

Conclusion

  • The research reveals that the SINE insertion alone is responsible for the “speed gene” effect in Thoroughbreds, significantly impacting a horse’s aptitude for specific race distances.

Cite This Article

APA
Rooney MF, Hill EW, Kelly VP, Porter RK. (2018). The “speed gene” effect of myostatin arises in Thoroughbred horses due to a promoter proximal SINE insertion. PLoS One, 13(10), e0205664. https://doi.org/10.1371/journal.pone.0205664

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 13
Issue: 10
Pages: e0205664
PII: e0205664

Researcher Affiliations

Rooney, Mary F
  • School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, Dublin 2, Ireland.
  • UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
Hill, Emmeline W
  • UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
Kelly, Vincent P
  • School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, Dublin 2, Ireland.
Porter, Richard K
  • School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, Dublin 2, Ireland.

MeSH Terms

  • Animals
  • Cell Line
  • Horses / genetics
  • Horses / metabolism
  • Introns
  • Muscle, Skeletal / metabolism
  • Mutagenesis, Insertional
  • Myostatin / biosynthesis
  • Myostatin / genetics
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Selective Breeding

Conflict of Interest Statement

EWH is Chief Science Officer of Plusvital Ltd. Plusvital Ltd. has been granted a licence for commercial use of the data that is contained within multiple granted patents and patent applications including (patent reference numbers): EP2352850, JP5667057, US8771943, AU2009290452, NZ591711, US9249470 and US2016215335. EWH is named on these patents. Plusvital Ltd. had no part in the research contained in this manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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