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Molecular phylogeny, long-term evolution, and functional divergence of flavin-containing monooxygenases

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Abstract

Flavin-containing monooxygenases (FMOs) metabolize xenobiotic compounds, many of which are clinically important, as well as endogenous substrates as part of a discrete physiological process. The FMO gene family is conserved and ancient with representatives present in all phyla so far examined. However, there is a lack of information regarding the long-term evolution and functional divergence of these proteins. This study represents the first attempt to characterize the long-term evolution followed by the members of this family. Our analysis shows that there is extensive silent divergence at the nucleotide level suggesting that this family has been subject to strong purifying selection at the protein level. Invertebrate FMOs have a polyphyletic origin. The functional divergence of FMOs 1–5 started before the split between amphibians and mammals. The vertebrate FMO5 is more ancestral than other four FMOs. Moreover, the existence of higher levels of codon bias was detected at the N-terminal ends, which can be ascribed to the critical role played by the FAD binding motif in this region. Finally, critical amino acid residues for FMO functional divergence (type I & II) after gene duplication were detected and characterized.

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Acknowledgments

This study was supported by China Postdoctoral Science Foundation (project 20080440019), Education Department of Liaoning Province (2009A120), and the Start-up Research Fund (2008) of Dalian Jiaotong University of China. We are grateful to Dr. William J. Etges and the anonymous reviewers for their critical comments and suggestions.

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Authors and Affiliations

  1. Laboratory of Biotechnology, Dalian Jiaotong University, 116028, Dalian, China

    Da Cheng Hao & Jun Mu

  2. Chinese Academy of Medical Sciences, Peking Union Medical College, 100193, Beijing, China

    Da Cheng Hao, Shi Lin Chen & Pei Gen Xiao

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  1. Da Cheng Hao
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  2. Shi Lin Chen
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  3. Jun Mu
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  4. Pei Gen Xiao
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Correspondence to Shi Lin Chen.

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Hao, D.C., Chen, S.L., Mu, J. et al. Molecular phylogeny, long-term evolution, and functional divergence of flavin-containing monooxygenases. Genetica 137, 173–187 (2009). https://doi.org/10.1007/s10709-009-9382-y

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