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

Autor: Rooney MF; 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 EW; UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland., Kelly VP; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, Dublin 2, Ireland., Porter RK; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, Dublin 2, Ireland.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Oct 31; Vol. 13 (10), pp. e0205664. Date of Electronic Publication: 2018 Oct 31 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0205664
Abstrakt: 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.
Competing Interests: 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.
Databáze: MEDLINE
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