Recent evolution of the salivary mucin MUC7.
Recent evolution of the salivary mucin MUC7.
复制标题
唾液粘蛋白MUC7的最新进化。
DOI：
10.1038/srep31791
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发表时间：
2016
影响因子：
4.6
通讯作者：
Gokcumen,Omer
中科院分区：
文献类型：
--
作者：
Xu,Duo;Pavlidis,Pavlos;Thamadilok,Supaporn;Redwood,Emilie;Fox,Sara;Blekhman,Ran;Ruhl,Stefan;Gokcumen,Omer
基因组结构变异构成了灵长类基因组中大部分可变碱基对，并以多种方式影响基因功能。虽然整个基因的重复和缺失已经得到了比较充分的研究，但外显子下的生物学（即，在编码外显子序列内），拷贝数变异仍然难以捉摸。唾液MUC7基因为研究这种变异提供了机会，因为它含有拷贝数可变的外显子下重复序列，编码具有微生物结合特性的密集O-糖基化结构域（PTS-重复）。为了了解这个基因的进化，我们在比较框架内分析了哺乳动物和灵长类动物的基因组。我们的分析表明：（i）MUC 7已出现在胎盘哺乳动物祖先中，并迅速获得多个O-糖基化位点;（ii）MUC 7在胎盘哺乳动物的唾液中保留了其细胞外活性;（iii）该蛋白的抗真菌结构域在灵长类谱系中的正选择下被重新修饰;和（iv）MUC 7 PTS重复序列在适应性约束下循环进化。我们的研究结果确立MUC7作为唾液适应的主要参与者，可能是灵长类动物对不同病原体暴露的反应。在更广泛的范围内，我们的研究强调了可变的外显子下重复序列作为模块化进化创新的主要来源，导致快速的功能适应。
Genomic structural variants constitute the majority of variable base pairs in primate genomes and affect gene function in multiple ways. While whole gene duplications and deletions are relatively well-studied, the biology of subexonic (i.e., within coding exon sequences), copy number variation remains elusive. The salivaryMUC7gene provides an opportunity for studying such variation, as it harbors copy number variable subexonic repeat sequences that encode for densely O-glycosylated domains (PTS-repeats) with microbe-binding properties. To understand the evolution of this gene, we analyzed mammalian and primate genomes within a comparative framework. Our analyses revealed that (i)MUC7has emerged in the placental mammal ancestor and rapidly gained multiple sites for O-glycosylation; (ii) MUC7 has retained its extracellular activity in saliva in placental mammals; (iii) the anti-fungal domain of the protein was remodified under positive selection in the primate lineage; and (iv)MUC7PTS-repeats have evolved recurrently and under adaptive constraints. Our results establishMUC7as a major player in salivary adaptation, likely as a response to diverse pathogenic exposure in primates. On a broader scale, our study highlights variable subexonic repeats as a primary source for modular evolutionary innovation that lead to rapid functional adaptation.