Nebulin: A Study of Protein Repeat Evolution
Nebulin: A Study of Protein Repeat Evolution
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DOI：
10.1016/j.jmb.2010.07.011
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发表时间：
2010-09-10
影响因子：
5.6
通讯作者：
Elofsson, Arne
中科院分区：
文献类型：
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作者：
Bjorklund, Asa K.;Light, Sara;Elofsson, Arne
蛋白质结构域重复在细胞组织的核心蛋白质中很常见，特别是在真核生物中。众所周知，它们是通过内部串联复制进化的。然而，对底层机制的理解并不完整。为了阐明重复扩展机制，我们研究了肌肉蛋白 Nebulin 的进化，该蛋白包含大量肌动蛋白结合 Nebulin 结构域。 Nebulin 蛋白是从包含两个 Nebulin 结构域的无脊椎动物前体进化而来的。重复区域通过单个结构域的复制以及由七个星云蛋白组成的超级重复（SR）的复制而扩展。我们表明，SR 至少在三种情况下独立进化为大区域：无脊椎动物佛罗里达文昌鱼两次，脊椎动物一次。深入分析揭示了 Nebulin 基因中最近的几个串联重复。这些事件涉及单域和多域SR单元或多个SR单元。虽然有单一事件，但同一单位经常会重复多次。例如，人类和黑猩猩的祖先经历了两次串联复制。复制连接点与 Alu 转座子一致，因此表明通过 Alu 介导的同源重组进行复制。SR 区域中的复制始终涉及七个结构域的倍数。然而，复制的确切单位在物种之间和物种内部都有所不同。因此，同一基序的多次串联重复不会产生大的 Nebulin 蛋白。最后，对人类基因组中片段重复的分析表明，重复在包含结构域重复的基因中比在编码非重复蛋白的基因中更常见。事实上，在长重复基因中发现片段重复的频率是偶然预期的三到六倍。 (C) 2010 Elsevier Ltd. 保留所有权利。
Protein domain repeats are common in proteins that are central to the organization of a cell, in particular in eukaryotes. They are known to evolve through internal tandem duplications. However, the understanding of the underlying mechanisms is incomplete. To shed light on repeat expansion mechanisms, we have studied the evolution of the muscle protein Nebulin, a protein that contains a large number of actin-binding nebulin domains.Nebulin proteins have evolved from an invertebrate precursor containing two nebulin domains. Repeat regions have expanded through duplications of single domains, as well as duplications of a super repeat (SR) consisting of seven nebulins. We show that the SR has evolved independently into large regions in at least three instances: twice in the invertebrate Branchiostoma floridae and once in vertebrates.In-depth analysis reveals several recent tandem duplications in the Nebulin gene. The events involve both single-domain and multidomain SR units or several SR units. There are single events, but frequently the same unit is duplicated multiple times. For instance, an ancestor of human and chimpanzee underwent two tandem duplications. The duplication junction coincides with an Alu transposon, thus suggesting duplication through Alu-mediated homologous recombination.Duplications in the SR region consistently involve multiples of seven domains. However, the exact unit that is duplicated varies both between species and within species. Thus, multiple tandem duplications of the same motif did not create the large Nebulin protein.Finally, analysis of segmental duplications in the human genome reveals that duplications are more common in genes containing domain repeats than in those coding for nonrepeated proteins. In fact, segmental duplications are found three to six times more often in long repeated genes than expected by chance. (C) 2010 Elsevier Ltd. All rights reserved.