Phylogenetic analysis of kindlins suggests subfunctionalization of an ancestral unduplicated kindlin into three paralogs in vertebrates.
Phylogenetic analysis of kindlins suggests subfunctionalization of an ancestral unduplicated kindlin into three paralogs in vertebrates.
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DOI：
10.4137/ebo.s6179
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发表时间：
2011-03-22
期刊：
影响因子：
--
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Khan AA;Janke A;Shimokawa T;Zhang H
Kindlin蛋白是一个新发现的进化保守的含FERM结构域的蛋白家族。该家族包括三个高度保守的蛋白质：Kindlin-1、Kindlin-2和Kindlin-3。所有这三种Kindlin蛋白都与局灶性粘连有关，并参与整合素的激活。每个Kindlin的FERM结构域都是两部分的，在整合素的激活过程中起着关键作用。在此，我们首次探索了这些蛋白质的进化史。Kindlins的系统发育表明，即使在最早的后生动物即九头蛇中也存在单一的祖先Kindlin蛋白。然后这种蛋白质在昆虫中经历了复制事件，在脊椎动物中也经历了基因组复制，导致了Kindlin家族。对Kindlin对虾的比较研究表明，Kindlin-2是这三个家族成员中进化最慢的蛋白质。对不同物种同源和非同义Kindlin序列的同义和非同义替换的分析表明，这三个Kindlin都是在净化选择的影响下进化的。Kindlins的表达模式和系统发育研究支持基因复制的亚功能化模型。
Kindlin proteins represent a newly discovered family of evolutionarily conserved FERM domain-containing proteins. This family includes three highly conserved proteins: Kindlin-1, Kindlin-2 and Kindlin-3. All three Kindlin proteins are associated with focal adhesions and are involved in integrin activation. The FERM domain of each Kindlin is bipartite and plays a key role in integrin activation. We herein explore for the first time the evolutionary history of these proteins. The phylogeny of the Kindlins suggests a single ancestral Kindlin protein present in even the earliest metazoan ie, hydra. This protein then underwent duplication events in insects and also experienced genome duplication in vertebrates, leading to the Kindlin family. A comparative study of the Kindlin paralogs showed that Kindlin-2 is the slowest evolving protein among the three family members. The analysis of synonymous and non-synonymous substitutions in orthologous Kindlin sequences in different species showed that all three Kindlins have been evolving under the influence of purifying selection. The expression pattern of Kindlins along with phylogenetic studies supports the subfunctionalization model of gene duplication.