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混杂蛋白质功能的“进化能力”

The 'evolvability' of promiscuous protein functions.

作者信息

Aharoni Amir, Gaidukov Leonid, Khersonsky Olga, McQ Gould Stephen, Roodveldt Cintia, Tawfik Dan S

机构信息

Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.

出版信息

Nat Genet. 2005 Jan;37(1):73-6. doi: 10.1038/ng1482. Epub 2004 Nov 28.

DOI:10.1038/ng1482
PMID:15568024
Abstract

How proteins with new functions (e.g., drug or antibiotic resistance or degradation of man-made chemicals) evolve in a matter of months or years is still unclear. This ability is dependent on the induction of new phenotypic traits by a small number of mutations (plasticity). But mutations often have deleterious effects on functions that are essential for survival. How are these seemingly conflicting demands met at the single-protein level? Results from directed laboratory evolution experiments indicate that the evolution of a new function is driven by mutations that have little effect on the native function but large effects on the promiscuous functions that serve as starting point. Thus, an evolving protein can initially acquire increased fitness for a new function without losing its original function. Gene duplication and the divergence of a completely new protein may then follow.

摘要

具有新功能的蛋白质(如抗药或抗抗生素能力,或对人造化学物质的降解能力)如何在数月或数年的时间内进化,目前仍不清楚。这种能力取决于少数突变(可塑性)诱导新的表型特征。但突变往往会对生存所必需的功能产生有害影响。在单蛋白水平上,这些看似相互矛盾的需求是如何得到满足的呢?定向实验室进化实验的结果表明,新功能的进化是由对天然功能影响较小但对作为起点的混杂功能影响较大的突变驱动的。因此,一个正在进化的蛋白质最初可以在不丧失其原始功能的情况下,获得对新功能的更高适应性。随后可能会发生基因复制和全新蛋白质的分化。

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