Evolution of cytochrome P-450 proteins

Thirty-four cytochrome P-450 sequences from one bacterial and six vertebrate species have been aligned with the aid of a computer alignment algorithm. Phylogenetic trees were constructed using the unweighted-pair-group and neighbor-joining methods. The two trees differed at only a single branch poin...

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Bibliographic Details
Published in:Molecular biology and evolution 1987-11, Vol.4 (6), p.572-593
Main Authors: NELSON, D. R, STROBEL, H. W
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Bacterial Proteins - genetics
Biological and medical sciences
Biological Evolution
Cytochrome P-450 Enzyme System - genetics
Fundamental and applied biological sciences. Psychology
Genetics of eukaryotes. Biological and molecular evolution
Humans
Molecular Sequence Data
Multigene Family
Phylogeny
Time Factors
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Summary:Thirty-four cytochrome P-450 sequences from one bacterial and six vertebrate species have been aligned with the aid of a computer alignment algorithm. Phylogenetic trees were constructed using the unweighted-pair-group and neighbor-joining methods. The two trees differed at only a single branch point near the base of the tree. The cytochrome P-450 superfamily of proteins clustered into eight families and contained 16 gene-duplication events. The first gene duplication occurred approximately 1,360 Myr before the present (Mybp) and gave rise to cytochrome P-450s found in two different cellular organelles, the mitochondria and the endoplasmic reticulum. Both groups utilize cholesterol or its metabolites as substrates, implying that cholesterol existed greater than 1,360 Mybp. The fourth gene duplication (approximately 900 Mybp) gave rise to the drug-metabolizing P-450s. These proteins aid in the detoxification of foreign chemicals, as opposed to the metabolism of endogenous compounds. The importance of the capacity to metabolize drugs is reflected in 11 further gene duplications occurring in this lineage. The first occurred approximately 800 Mybp and gave rise to the two major P-450 families, the phenobarbital and 3-methylcholanthrene families. An apparent increase in the rate of cytochrome P-450 evolution is noted between the bird-mammal divergence (300 Mybp) and the mammalian radiation (75 Mybp).
ISSN:0737-4038
1537-1719
1537-1719
DOI:10.1093/oxfordjournals.molbev.a040471