Journal of Molecular Evolution

, Volume 57, Issue 2, pp 200–211

Phylogenetic Analysis of the Cytochrome P450 3 (CYP3) Gene Family

Authors

  • Andrew G. McArthur
    • The Josephine Bay Paul Center for Comparative Molecular Biology and EvolutionMarine Biological Laboratory, Woods Hole, MA 02543
  • Tove Hegelund
    • Department of ZoologyGöteborg University, Box 463, SE 405 30 Göteborg
  • Rachel L. Cox
    • Biology DepartmentWoods Hole Oceanographic Institution, Woods Hole, MA 02543
  • John J. Stegeman
    • Biology DepartmentWoods Hole Oceanographic Institution, Woods Hole, MA 02543
  • Mette Liljenberg
    • Department of ZoologyGöteborg University, Box 463, SE 405 30 Göteborg
  • Urban Olsson
    • Department of ZoologyGöteborg University, Box 463, SE 405 30 Göteborg
  • Per Sundberg
    • Department of ZoologyGöteborg University, Box 463, SE 405 30 Göteborg
    • Department of ZoologyGöteborg University, Box 463, SE 405 30 Göteborg
Article

DOI: 10.1007/s00239-003-2466-x

Cite this article as:
McArthur, A.G., Hegelund, T., Cox, R.L. et al. J Mol Evol (2003) 57: 200. doi:10.1007/s00239-003-2466-x

Abstract

Cytochrome P450 genes (CYP) constitute a superfamily with members known from the Bacteria, Archaea, and Eukarya. The CYP3 gene family includes the CYP3A and CYP3B subfamilies. Members of the CYP3A subfamily represent the dominant CYP forms expressed in the digestive and respiratory tracts of vertebrates. The CYP3A enzymes metabolize a wide variety of chemically diverse lipophilic organic compounds. To understand vertebrate CYP3 diversity better, we determined the killifish (Fundulus heteroclitus) CYP3A30 and CYP3A56 and the ball python (Python regius) CYP3A42 sequences. We performed phylogenetic analyses of 45 vertebrate CYP3 amino acid sequences using a Bayesian approach. Our analyses indicate that teleost, diapsid, and mammalian CYP3A genes have undergone independent diversification and that the ancestral vertebrate genome contained a single CYP3A gene. Most CYP3A diversity is the product of recent gene duplication events. There is strong support for placement of the guinea pig CYP3A genes within the rodent CYP3A diversification. The rat, mouse, and hamster CYP3A genes are mixed among several rodent CYP3A subclades, indicative of a complex history involving speciation and gene duplication. Phylogenetic analyses suggest two CYP3A gene duplication events early in rodent history, with the rat CYP3A9 and mouse Cyp3a13 clade having a sister relationship to all other rodent CYP3A genes. In primate history, the human CYP3A43 gene appears to have a sister relationship to all other known primate CYP3A genes. Other, more recent gene duplications are hypothesized to have occurred independently within the human, pig, rat, mouse, guinea pig, and fish genomes. Functional analyses suggest that gene duplication is strongly tied to acquisition of new function and that convergent evolution of CYP3A function may be frequent among independent gene copies.

Keywords

Cytochrome P450CYP3APhylogenyVertebrataMammaliaRodentia

Copyright information

© Springer-Verlag New York Inc. 2003