摘要
Flavin-containing monooxygenase (FMO), like cytochrome P450 (CYP), is a monooxygenase that uses the reducing equivalents of NADPH to reduce one atom of molecular oxygen to water, while the other atom is used to oxidize the substrate. Recently, it was shown that some CYP isoforms have been subject to positive selection. However, it is unknown whether the highly conserved phase I detoxification enzyme, FMO, has undergone similar positive Darwinian selection. We used maximum-likelihood models of codon substitution, evolutionary fingerprinting, and cross species comparison to investigate the occurrence of adaptive evolution in FMO sequences. We used recent genomic data from a range of species, including vertebrates and invertebrates. We present the evidence for the occurrence of adaptive evolution in mammalian FMO 3, 4, 5, and fugu FMOs but not in mammalian FMO 1, FMO 2, frog FMOs, other fish FMOs and invertebrate FMOs. The sites under adaptive evolution were significantly associated with the insertion domain in mammalian FMO 5. We identified specific amino acid sites in FMOs 3–5 that are likely targets for selection based on the patterns of parallel amino acid change. The most likely role of adaptive evolution is the repair of mutations that permitted optimal NADP+ binding and improved catalytic efficiency. The occurrence of positive selection during the evolution of phase I detoxification enzymes such as FMOs 3–5 and fugu FMO suggests the occurrence of both high selection pressure acting on species within their unique habitats and significant changes in intensity and direction (forms of xenobiotics and drugs) resulting from changes in microhabitat and food.
Flavin-containing monooxygenase （FMO）, like cytochrome P450 （CYP）, is a monooxygenase that uses the reducing equivalents of NADPH to reduce one atom of molecular oxygen to water, while the other atom is used to oxidize the substrate. Recently, it was shown that some CYP isoforms have been subject to positive selection. However, it is unknown whether the highly conserved phase I detoxification enzyme, FMO, has undergone similar positive Darwinian selection. We used maximum-likelihood models of codon substitution, evolutionary fingerprinting, and cross species comparison to investigate the occurrence of adaptive evolution in FMO sequences. We used recent genomic data from a range of species, including vertebrates and invertebrates. We present the evidence for the occurrence of adaptive evolution in mammalian FMO 3, 4, 5, and fugu FMOs but not in mammalian FMO 1, FMO 2, frog FMOs, other fish FMOs and invertebrate FMOs. The sites under adaptive evolution were significantly associated with the insertion domain in mammalian FMO 5. We identified specific amino acid sites in FMOs 3-5 that are likely targets for selection based on the patterns of parallel amino acid change. The most likely role of adaptive evolution is the repair of mutations that permitted optimal NADP＋ binding and improved catalytic efficiency. The occurrence of positive selection during the evolu- tion of phase I detoxification enzymes such as FMOs 3-5 and fugu FMO suggests the occurrence of both high selection pressure acting on species within their unique habitats and significant changes in intensity and direction （forms of xenobiotics and drugs） resulting from changes in microhabitat and food.
基金
supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China (2008ZX10005-004)
Educational Commission of Liaoning Province of China (2009A120)
China Postdoctoral Science Foundation (20080440019 and 200902069)
关键词
适应性进化
单加氧酶
选择模式
网站
细胞色素P450
无脊椎动物
FMOs
预测
flavin-containing monooxygenase, adaptive evolution, positive selection, insertion domain, evolutionary fingerprint,maximum likelihood
