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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Clathrin heavy and light chain isoforms originated by independent mechanisms of gene duplication during chordate evolution
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Clathrin heavy and light chain isoforms originated by independent mechanisms of gene duplication during chordate evolution

机译：网格蛋白重链和轻链亚型起源于氯酸盐进化过程中基因复制的独立机制

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摘要

In humans, there are two isoforms each of clathrin heavy chain (CHC17 and CHC22) and light chain (LCa and LCb) subunits, all encoded by separate genes. CHC17 forms the ubiquitous clathrin-coated vesicles that mediate membrane traffic. CHC22 is implicated in specialized membrane organization in skeletal muscle. CHC17 is bound and regulated by LCa and LCb, whereas CHC22 does not functionally interact with either light chain. The imbalanced interactions between clathrin subunit isoforms suggest a distinct evolutionary history for each isoform pair. Phylogenetic and sequence analysis placed both heavy and light chain gene duplications during chordate evolution, 510-600 million years ago. Genes encoding CHC22 orthologues were found in several vertebrate species, with only a pseudogene present in mice. Multiple paral-ogons surrounding the CHC genes (CLTC and CLTD) were identified, evidence that genomic or large-scale gene duplication produced the two CHC isoforms. In contrast, clathrin light chain genes (CLTA and CLTB) apparently arose by localized duplication, within 1-11 million years of CHC gene duplication. Analysis of sequence divergence patterns suggested that structural features of the CHCs were maintained after gene duplication, but new interactions with regulatory proteins evolved for the CHC22 isoform. Thus, independent mechanisms of gene duplication expanded clathrin functions, concomitant with development of neuromuscular sophistication in chordates.
机译：在人类中，网格蛋白重链（CHC17和CHC22）和轻链（LCa和LCb）亚基各有两个亚型，均由独立的基因编码。 CHC17形成无处不在的网格蛋白涂层囊泡，介导膜运输。 CHC22参与骨骼肌的专门膜组织。 CHC17受LCa和LCb约束并受其调控，而CHC22在功能上不与任一轻链相互作用。网格蛋白亚基同工型之间的不平衡相互作用表明每个同工型对都有独特的进化史。系统发育和序列分析在510-600百万年前的碳酸盐进化过程中放置​​了重链和轻链基因重复。在几种脊椎动物中发现了编码CHC22直向同源物的基因，小鼠中仅存在假基因。围绕CHC基因（CLTC和CLTD）的多个部分同源物被鉴定出来，证明基因组或大规模基因重复产生了这两种CHC亚型。相反，网格蛋白轻链基因（CLTA和CLTB）显然是在CHC基因复制的1到1百万年之内通过局部复制产生的。序列差异模式的分析表明，基因复制后CHC的结构特征得以保留，但与CHC22亚型的调节蛋白发生了新的相互作用。因此，基因复制的独立机制扩展了网格蛋白功能，并伴随着脊索神经肌肉发达的发展。

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