摘要
Human DHRS2 and DHRS4 genes code for similar NADP-dependent short-chain carbonyl-reductase enzymes having different substrate specificity. Human DHRS2 and DHRS4 enzymes share several common sequence motives including residues responsible for coenzyme binding as well as for the intimate catalytic oxido-reductase mechanism, while their substrate-binding sequences have very low similarity. We found that DHRS2 and DHRS4 genes are syntenic outparalogues originated from a duplication of the DHRS4 gene that took place before the formation of the mammalian clade. DHRS2 gene evolved more rapidly and underwent positive selection on more sites than the DHRS4 gene. DHRS2 sites under positive selection were mainly located on the enzyme active site thus showing that substrate specificity drove the divergence from the DHRS4 enzyme. Rapid divergent evolution brought the human DHRS2 enzyme to have subcellular localization, synthesis regulation and specialized cellular functions very different from those of the human DHRS4 enzyme.
摘要译文
人类DHRS2和DHRS4基因编码具有不同底物特异性的类似的NADP依赖性短链羰基还原酶的酶。人力DHRS2和DHRS4酶具有一些共同序列动机包括负责辅酶结合以及为贴心的催化氧化还原酶机制残留，而它们的底物结合序列有非常低的相似性。我们发现，DHRS2和DHRS4基因同线outparalogues源于DHRS4基因哺乳动物的进化枝的形成之前发生的重复。DHRS2基因进化得更快，并进行积极的选择上比DHRS4基因更多的网站。正选择DHRS2位点主要位于酶活性位点从而显示出底物特异性开车从DHRS4酶的发散。快速进化分歧所带来的人类DHRS2酶有亚细胞定位，综合监管和专门的细胞功能，从这些人的DHRS4酶的非常不同。
Franco Gabrielli[a]; Sergio Tofanelli[b]. Molecular and functional evolution of human DHRS2 and DHRS4 duplicated genes[J]. Gene, 2012,511(2): 461–469