Refining the Myostatin Gene Polymorphism through Worldwide Whole-Genome Sequencing.

Myostatin () is a highly conserved negative regulator of skeletal muscle in mammals. Inactivating mutations results in a hyper-muscularity phenotype known as "double muscling" in several livestock and model species. In , the gene structure organization and the sequence polymorphisms have been previously investigated, using Sanger and Next-Generation Sequencing technologies on a limited number of animals. Here, we carried out a follow-up study with the aim to further expand our knowledge about the sequence polymorphisms at the myostatin locus, through the whole-genome sequencing data of 183 samples representative of the geographical distribution range for this species. We focused our polymorphism analysis on the ±5 kb upstream and downstream region of the gene. A total of 99 variants (77 Single Nucleotide Polymorphisms and 22 indels) were observed. These were mainly located in intergenic and intronic regions, with only six synonymous Single Nucleotide Polymorphisms in exons. A sequence comparative analysis among the three species within the genus confirmed the expected higher genetic distance of from the wild and domestic two-humped camels compared to the genetic distance between and In silico functional prediction highlighted: (i) 213 differential putative transcription factor-binding sites, out of which 41 relative to transcription factors, with known literature evidence supporting their involvement in muscle metabolism and/or muscle development; and (ii) a number of variants potentially disrupting the canonical splicing elements, out of which two are discussed here for their potential ability to generate a prematurely truncated (inactive) form of the protein. The distribution of the considered variants in the studied cohort is discussed in light of the peculiar evolutionary history of this species and the hypothesis that extremely high muscularity, associated with a homozygous condition for mutated (inactivating) alleles at the myostatin locus, may represent, in arid desert conditions, a clear metabolic disadvantage, emphasizing the thermoregulatory and water availability challenges typical of these habitats.