Prediction of sites under adaptive evolution in flavin-containing monooxygenases: Selection pattern revisited |
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Authors: | DaCheng Hao PeiGen Xiao |
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Institution: | (1) Biotechnology Institute, Dalian Jiaotong University, Dalian, 116028, China;(2) Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China |
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Abstract: | 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. |
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Keywords: | flavin-containing monooxygenase adaptive evolution positive selection insertion domain evolutionary fingerprint maximum likelihood |
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