【摘要】 细胞色素P450(cytochrome P450,CYP)酶存在于所有哺乳动物中,它们从共同的祖先通过基因倍增进化而来,以一种"爆炸性"的趋势形成了庞大的超家族。除代谢脂质等内源性物质外,部分CYP酶还在药物等外源性物质的代谢方面起到重要作用。通过收集和注释哺乳动物CYP酶的序列发现,家族规模发生显著变化的七个活跃亚家族均属于CYP1~4家族,相比之下,非CYP1~4家族的家族规模则基本保持稳定。基于二级结构的预测结果,六段底物识别位点(substrate recognition sites,SRSs)的进化速率在CYP1~4家族中,特别是活跃的亚家族中,也显著快于非CYP1~4家族。同时,SRS1~3的进化速率显著快于SRS4~6,说明SRS1-3在更大程度上决定了CYP酶在进化过程中所获得的新功能。更多还原

【Abstract】 Cytochrome P450(CYPs) enzymes exist in all kinds of mammals, which are descended from a single common ancestor via gene duplication and constitute a large superfamily through the expansion.Besides the lipid metabolism, CYPs are also engaged in the xenobiotics biodegradation and metabolism,especially the members of human CYP1~4 families which play important roles in drug metabolism. Seven active subfamilies(CYP2A, CYP2 C, CYP2 D, CYP2 E, CYP2 J, CYP3 A and CYP4F) were found by sequence alignment and annotation, which have a strong trend to expand or shrink on the scale of family size during the evolution. In contrast, the family size of non-CYP1~4 families remains nearly the same among mammals.Evolutionary rates of six substrate recognition sites(SRSs) in CYP1~4 families, especially in the active subfamilies, are significantly higher than those in other families. In addition, SRS1~3 have faster evolutionary rates than SRS4~6, which indicates that SRS1~3 are more likely to determine the new functions of CYP enzymes during the evolution.更多还原