Phylogenomic analyses reveal the evolutionary origin of the inhibin alpha-subunit, a unique TGFbeta superfamily antagonist.

Phylogenomic analyses reveal the evolutionary origin of the inhibin alpha-subunit, a unique TGFbeta superfamily antagonist.
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DOI:
10.1371/journal.pone.0009457
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发表时间:
2010-03-04
期刊:
影响因子:
3.7
通讯作者:
Woodruff TK
Woodruff TK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhu J;Braun EL;Kohno S;Antenos M;Xu EY;Cook RW;Lin SJ;Moore BC;Guillette LJ Jr;Jardetzky TS;Woodruff TK

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转化生长因子-β(TGFR-β)同源物在动物进化早期形成了一个不同的超家族,通过跨膜、保守的丝氨酸-苏氨酸激酶(RII和RI受体)控制细胞功能。激活素和抑制素是转化生长因子β超家族中的相关二聚体,它们共享一个共同的β亚基。抑制素α亚基的进化创造了转化生长因子β超家族中唯一的拮抗剂,也是已知的唯一作为内分泌激素的成员。这种激素给脊椎动物的生殖功能带来了新的复杂性和控制力。抑制素α亚基的新功能似乎反映了在进化过程中抑制素β亚单位内发生的特定插入-缺失变化。利用系统基因组学分析,我们将特定的插入与不同功能的获得联系在一起,这些功能是脊椎动物生殖过程表型复杂性的基础。这种系统基因组学方法为理解抑制素、激活素和更大的转化生长因子β超家族之间的结构-功能关系提供了一种新的方法。
Transforming growth factor-beta (TGFβ) homologues form a diverse superfamily that arose early in animal evolution and control cellular function through membrane-spanning, conserved serine-threonine kinases (RII and RI receptors). Activin and inhibin are related dimers within the TGFβ superfamily that share a common β-subunit. The evolution of the inhibin α-subunit created the only antagonist within the TGFβ superfamily and the only member known to act as an endocrine hormone. This hormone introduced a new level of complexity and control to vertebrate reproductive function. The novel functions of the inhibin α-subunit appear to reflect specific insertion-deletion changes within the inhibin β-subunit that occurred during evolution. Using phylogenomic analysis, we correlated specific insertions with the acquisition of distinct functions that underlie the phenotypic complexity of vertebrate reproductive processes. This phylogenomic approach presents a new way of understanding the structure-function relationships between inhibin, activin, and the larger TGFβ superfamily.
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