Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.
BMC Evol Biol. 2012 Oct 8;12:202. doi: 10.1186/1471-2148-12-202.
Most fishes possess two paralogs for myostatin, a muscle growth inhibitor, while salmonids are presumed to have four: mstn1a, mstn1b, mstn2a and mstn2b, a pseudogene. The mechanisms responsible for preserving these duplicates as well as the depth of mstn2b nonfunctionalization within the family remain unknown. We therefore characterized several genomic clones in order to better define species and gene phylogenies.
Gene organization and sequence conservation was particularly evident among paralog groupings and within salmonid subfamilies. All mstn2b sequences included in-frame stop codons, confirming its nonfunctionalization across taxa, although the indels and polymorphisms responsible often differed. For example, the specific indels within the Onchorhynchus tshawytscha and O. nerka genes were remarkably similar and differed equally from other mstn2b orthologs. A phylogenetic analysis weakly established a mstn2b clade including only these species, which coupled with a shared 51 base pair deletion might suggest a history involving hybridization or a shared phylogenetic history. Furthermore, mstn2 introns all lacked conserved splice site motifs, suggesting that the tissue-specific processing of mstn2a transcripts, but not those of mstn2b, is due to alternative cis regulation and is likely a common feature in salmonids. It also suggests that limited transcript processing may have contributed to mstn2b nonfunctionalization.
Previous studies revealed divergence within gene promoters while the current studies provide evidence for relaxed or positive selection in some coding sequence lineages. These results together suggest that the salmonid myostatin gene family is a novel resource for investigating mechanisms that regulate duplicate gene fate as paralog specific differences in gene expression, transcript processing and protein structure are all suggestive of active divergence.
大多数鱼类拥有两个肌肉生长抑制素（myostatin）的同源基因，而鲑鱼科鱼类则被认为有四个：mstn1a、mstn1b、mstn2a 和 mstn2b（假基因）。负责保存这些副本的机制以及家族内 mstn2b 非功能化的深度仍然未知。因此，我们对几个基因组克隆进行了表征，以更好地定义物种和基因系统发育。
基因组织和序列保守性在同源基因群和鲑鱼科亚科内尤为明显。所有包含框内终止密码子的 mstn2b 序列都证实了其在整个分类群中的非功能化，尽管导致这些序列差异的插入缺失和多态性往往不同。例如，Onchorhynchus tshawytscha 和 O. nerka 基因中的特定插入缺失非常相似，并且与其他 mstn2b 直系同源物的差异相等。系统发育分析弱确立了一个仅包含这些物种的 mstn2b 分支，这与共享的 51 个碱基对缺失相结合，可能表明涉及杂交或共享进化史的历史。此外，mstn2 内含子都缺乏保守的剪接位点基序，这表明 mstn2a 转录物的组织特异性加工，而不是 mstn2b 转录物的加工，是由于顺式调控的替代，并且可能是鲑鱼科的一个共同特征。这也表明有限的转录加工可能导致 mstn2b 非功能化。
先前的研究揭示了基因启动子内的分化，而当前的研究提供了证据表明，在一些编码序列谱系中存在松弛或正选择。这些结果共同表明，鲑鱼科肌肉生长抑制素基因家族是研究调节重复基因命运的机制的新资源，因为基因表达、转录加工和蛋白质结构的同源基因特异性差异都表明存在活跃的分化。
