Refining the Camelus dromedarius Myostatin Gene Polymorphism through Worldwide Whole-Genome Sequencing

Abstract

Myostatin (MSTN) 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 Camelus dromedarius, 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 MSTN 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 Camelus genus confirmed the expected higher genetic distance of C. dromedarius from the wild and domestic two-humped camels compared to the genetic distance between C. bactrianus and C. ferus. 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 MSTN 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.

Analisis Keanekaragaman Gen Myostatin (Mstn) Secara in-Silico Pada Cattle Di Indonesia

“…Testosteron dan androgen lainnya juga berperan dalam mengatur myostatin, dengan penelitian yang menunjukkan bahwa pengebirian menyebabkan peningkatan ekspresi myostatin dan penurunan massa otot. Selain itu, ekspresi myostsatin diatur oleh berbagai jalur pensinyalan, termasuk jalur Smad, yang diaktifkan oleh pengikatan myostatin ke reseptornya, dan jalur Akt/mTOR, yang terlibat dalam sintesis protein otot (Bruno et al, 2022;Grade et al, 2019;Konovalova et al, 2021b).…”

“…Mutasi pada gen MSTN telah diidentifikasi pada pada Belgian Blue, Piedmontese, Aberdeen Angus, Limousin, dan Simmental. Secara nyata jika dilihat cattle dengan mutasi gen MSTN memiliki bentuk tubuh yang lebih kekar (Bi et al, 2020;Bruno et al, 2022;Grade et al, 2019). Seperti contoh, Mutasi nt821 (del11) dikaitkan dengan cacat genetik otot ganda pada Belgian Blue, sedangkan mutasi F94L telah terbukti memiliki efek aditif pada sifat karkas pada beberapa jenis cattle.…”

Exploiting morphobiometric and genomic variability of African indigenous camel populations-A review

“…Similar SNP (C/T) was found at positions 062 and 232, respectively in Nigerian indigenous camels ( Ibrahim et al, 2022 ). In a related study of the myostatin (MSTN) gene, which affects muscularity (Ramadan and Inoue-Murayama; Bruno et al, 2022 ) using twenty two camel samples from Tunisia, Algeria, and Egypt, Muzzachi et al (2015) found at intron 1, G486C, G798A and C799T substitutions. This could be a reflection of the peculiarity of the evolutionary history of camels in the three north African countries.…”

A Genome-Wide Association Study of the Chest Circumference Trait in Xinjiang Donkeys Based on Whole-Genome Sequencing Technology

“…In the last decade, various GWAS studies have been undertaken on livestock, including socially affected traits and body mass index in Yorkshire pigs [32,33], coat color traits in Arab camels and cattle [34,35], meat quality in camels [36], foot and leg conformation traits in Chinese Holstein cattle [37], milk fatty acid traits in Comisana sheep [38], litter size in sheep [39], body weight traits in yaks [40], growth traits in Braunvieh cattle [41], and growth traits in broilers [42]. Whole-genome sequencing has been used to detect population structures and to identify polymorphisms that might affect the economic traits of livestock animals [43].…”