NDLI: Phylogenetic and Functional Analysis of the Vertebrate Cytochrome P450 2 Family

Content Provider	Springer Nature Link
Author	Kirischian, Nina McArthur, Andrew G. Jesuthasan, Caroline Krattenmacher, Birgit Wilson, Joanna Y.
Copyright Year	2010
Abstract	Cytochrome P450 (CYP) proteins compose a highly diverse superfamily found in all domains of life. These proteins are enzymes involved in metabolism of endogenous and exogenous compounds. In vertebrates, the CYP2 family is one of the largest, most diverse and plays an important role in mammalian drug metabolism. However, there are more than 20 vertebrate CYP2 subfamilies with uncertain evolution and fairly discrete subfamily composition within vertebrate classes, hindering extrapolation of knowledge across subfamilies. To better understand CYP2 diversity, a phylogenetic analysis of 196 CYP2 protein sequences from 16 species was performed using a maximum likelihood approach and Bayesian inference. The analyses included the CYP2 compliment from human, fugu, zebrafish, stickleback, medaka, cow, and dog genomes. Additional sequences were included from rabbit, marsupial, platypus, chicken, frog, and salmonid species. Three CYP2 sequences from the tunicate Ciona intestinalis were utilized as the outgroup. Results indicate a single ancestral vertebrate CYP2 gene and monophyly of all CYP2 subfamilies. Two subfamilies (CYP2R and CYP2U) pre-date vertebrate diversification, allowing direct comparison across vertebrate classes, while all other subfamilies originated during vertebrate diversification, often within specific vertebrate lineages. Analysis of site-specific evolution indicates that some substrate recognition sites (SRS) previously proposed for CYP genes do not have elevated rates of evolution, suggesting that these regions of the protein are not necessarily important in recognition of CYP2 substrates. Type II functional divergence analysis identified multiple residues in the active site of CYP2F, CYP2A, and CYP2B proteins that have undergone radical biochemical changes and may be functionally important.
Starting Page	56
Ending Page	71
Page Count	16
File Format	PDF
ISSN	00222844
Journal	Journal of Molecular Evolution
Volume Number	72
Issue Number	1
e-ISSN	14321432
Language	English
Publisher	Springer-Verlag
Publisher Date	2010-11-30
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cytochrome P450 Vertebrate CYP2 phylogeny Functional divergence P450 active sites Animal Genetics and Genomics Plant Genetics & Genomics Plant Sciences Microbiology Evolutionary Biology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Genetics Molecular Biology Ecology, Evolution, Behavior and Systematics

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