Evolution of the cytochrome P450 superfamily:: sequence alignments and pharmacogenetics
Evolution of the cytochrome P450 superfamily:: sequence alignments and pharmacogenetics
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DOI：
10.1016/s1383-5742(97)00040-9
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发表时间：
1998-06-01
影响因子：
5.3
通讯作者：
Lake, BG
中科院分区：
文献类型：
--
作者：
Lewis, DFV;Watson, E;Lake, BG
描述了细胞色素P450（P450）超家族的进化，特别是在地质时期生物形式发展中的重大事件。据指出，目前公认的P450系统发生树的时间尺度与陆地生物区系的进化密切相关。事实上，目前人类的P450外源性代谢酶可能起源于大约4亿年前泥盆纪时期植物和动物之间的共同进化“战争”。随着时间的推移，P450系统的进化和生物发展过程之间的一些关键对应关系指向进化的机制分子生物学，这与20亿年前开始的大气氧合稳定增加一致，而最近地质时期的饮食变化可能为某些物种的代谢差异提供一种可能的解释。同一家族或亚家族内P450蛋白序列之间的比对，以及跨家族比较，有助于合理化不同P450亚型的药物代谢特异性，并有助于在分子水平上理解P450介导的氧化的遗传多态性。此外，不同哺乳动物物种之间P450调节机制和诱导性的差异可能对目前的化学品安全评价程序产生重要影响，这些程序依赖于实验室饲养的啮齿动物的纯遗传品系来测试人类接触的化合物。(C)1998 Elsevier Science B.V.保留所有权利。
The evolution of the cytochrome P450 (CYP) superfamily is described, with particular reference to major events in the development of biological forms during geological time. It is noted that the currently accepted timescale for the elaboration of the P450 phylogenetic tree exhibits close parallels with the evolution of terrestrial biota. Indeed, the present human P450 complement of xenobiotic-metabolizing enzymes may have originated from coevolutionary 'warfare' between plants and animals during the Devonian period about 400 million years ago. A number of key correspondences between the evolution of P450 system and the course of biological development over time, point to a mechanistic molecular biology of evolution which is consistent with a steady increase in atmospheric oxygenation beginning over 2000 million years ago, whereas dietary changes during more recent geological time may provide one possible explanation for certain species differences in metabolism. Alignment between P450 protein sequences within the same family or subfamily, together with across-family comparisons, aid the rationalization of drug metabolism specificities for different P450 isoforms, and can assist in an understanding of genetic polymorphisms in P450-mediated oxidations at the molecular level. Moreover, the variation in P450 regulatory mechanisms and inducibilities between different mammalian species are likely to have important implications for current procedures of chemical safety evaluation, which rely on pure genetic strains of laboratory bred rodents for the testing of compounds destined for human exposure. (C) 1998 Elsevier Science B.V. All rights reserved.