Evolution of myostatin in vertebrates: is there evidence for positive selection?

Evolution of myostatin in vertebrates: is there evidence for positive selection?
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DOI:
10.1016/j.ympev.2006.05.038
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发表时间:
2006-12
影响因子:
4.1
通讯作者:
M. Pie;L. E. Alvares
M. Pie;L. E. Alvares
中科院分区:
生物学1区
文献类型:
--
作者:
M. Pie;L. E. Alvares

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转化生长因子(TGF-)超家族包括负责调节多种影响胚胎发育和组织稳态的细胞功能的信号多肽(Herpin et al., 2004)。肌生长抑制素,也被称为生长与分化因子-8 (GDF-8),是tgf超家族的一员,由于其作为脊椎动物肌肉生长的负调节因子的作用,在过去几年中受到了相当大的关注(McPherron等人,1997;Grobet等人,1997,1998;Kambadur等人,1997;Radaelli等人,2003)。肌肉生长抑制素控制肌肉生长的机制似乎是基于通过刺激细胞周期退出来抑制成肌细胞增殖,同时抑制分化和诱导细胞静止(Thomas等)。, 2000)。预测的人类、大鼠、小鼠、猪、鸡和火鸡的肌肉生长抑制素蛋白在生物活性羧基末端区域是相同的,这表明该基因在脊椎动物进化过程中是高度保守的(McPherron和Lee, 1997)。鉴于其在胚胎发生过程中调节肌肉质量沉积的关键作用,可以预期肌肉生长抑制素将受到强烈的净化选择,以使骨骼肌在脊椎动物体内达到理想的大小。然而,最近的研究提供了对肌肉生长抑制素的积极选择的证据,特别是在偶蹄类哺乳动物和硬骨鱼中(Limberles等,2001;Tellgren等,2004)。在蛋白质编码基因中,正选择可以通过计算每个非同义位点(dN)的非同义(氨基酸改变)核苷酸取代率与每个同义位点(dS)的同义取代离子率之间的比率来检测,通常称为(Hughes和Nei, 1989)。当>为1时,我们认为正选择在起作用,而当> < 1时,我们认为这是净化选择的证据。在这项研究中,我们采用最大似然方法研究了哺乳动物、鸟类和鱼类的肌肉生长抑制素基因的选择模式。有趣的是,所有的分析都未能在研究序列中检测到正选择。更确切地说,无论分类群如何,都存在强烈的净化选择。讨论了本研究结果与前人研究结果存在差异的原因。
The transforming growth factor (TGF-) superfamily includes signaling polypeptides that are responsible for regulating a variety of cellular functions that affect embryo development and tissue homeostasis (Herpin et al., 2004). Myostatin, also known as growth and differentiation factor-8 (GDF-8), is a member of the TGF-superfamily that has received considerable attention in the past few years due to its role as a negative regulator of vertebrate muscle growth (McPherron et al., 1997; Grobet et al., 1997, 1998; Kambadur et al., 1997; Radaelli et al., 2003). The myostatin mechanism for controlling muscle growth seems to be based on the inhibition of myoblast proliferation by stimulating cell cycle withdrawal while simultaneously inhibiting differentiation and inducing cellular quiescence (Thomas etal., 2000). The predicted human, rat, mouse, porcine, chicken, and turkey myostatin proteins are identical in the biologically active carboxy-terminal region, suggesting that this gene is highly conserved throughout vertebrate evolution (McPherron and Lee, 1997). Given its key role in the regulation of muscle mass deposition during embryogenesis, one could expect that myostatin would be subject to strong purifying selection to allow skeletal muscles to achieve their ideal size in the body of vertebrate organisms. However, recent studies have presented evidence of positive selection on myostatin, particularly in artiodactylid mammals and teleost fish (Limberles et al., 2001; Tellgren et al., 2004). In proteincoding genes, positive selection might be detected by computing the ratio between the rate of nonsynonymous (amino acid altering) nucleotide substitutions per nonsynonymous site (dN) and the rate of synonymous substitut ion per synonymous site (dS), commonly referred to as (Hughes and Nei, 1989). When> 1, positive selection is said to be operating, whereas a< 1 could be interpreted as evidence of purifying selection. In this study we employ maximum likelihood methods to investigate the pattern of selection in the myostatin gene in a comprehensive sample of mammals, birds, and fish. Interestingly, all of the analyses failed to detect positive selection in the studied sequences. Rather, strong purifying selection was present, irrespective of the taxonomic group. The reasons for the discrepancy between our results and previous studies are discussed.