Bruno Silvia, Landi Vincenzo, Senczuk Gabriele, Brooks Samantha Ann, Almathen Faisal, Faye Bernard, Gaouar Suheil Semir Bechir, Piro Mohammed, Kim Kwan Suk, David Xavier, Eggen André, Burger Pamela, Ciani Elena
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "Aldo Moro", 70126 Bari, Italy.
Department of Veterinary Medicine, University of Bari "Aldo Moro", Valenzano, 70010 Bari, Italy.
Animals (Basel). 2022 Aug 14;12(16):2068. doi: 10.3390/ani12162068.
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.
肌肉生长抑制素（）是哺乳动物骨骼肌中一种高度保守的负调控因子。失活突变在几种家畜和模型物种中导致一种称为“双肌”的肌肉过度发育表型。在之前的研究中，已使用桑格测序法和新一代测序技术对有限数量的动物进行了该基因的结构组织和序列多态性研究。在此，我们开展了一项后续研究，旨在通过对代表该物种地理分布范围的183个样本的全基因组测序数据，进一步扩展我们对肌肉生长抑制素基因座序列多态性的认识。我们将多态性分析集中在该基因上下游±5 kb的区域。共观察到99个变异（77个单核苷酸多态性和22个插入/缺失）。这些变异主要位于基因间区和内含子区，外显子中仅有6个同义单核苷酸多态性。该属内三个物种之间的序列比较分析证实，与野生双峰驼和家养双峰驼相比，预期与之间的遗传距离更大。计算机功能预测突出显示：（i）213个差异推定转录因子结合位点，其中41个与转录因子相关，有已知文献证据支持它们参与肌肉代谢和/或肌肉发育；（ii）一些变异可能破坏典型的剪接元件，其中两个在此讨论其产生蛋白质过早截短（无活性）形式的潜在能力。根据该物种独特的进化历史以及以下假设，讨论了所考虑变异在研究群体中的分布：在干旱沙漠条件下，与肌肉生长抑制素基因座突变（失活）等位基因的纯合状态相关的极高肌肉量可能代表明显的代谢劣势，强调了这些栖息地典型的体温调节和水供应挑战。
