Molecular Biology and Evolution, Vol 4, 572-593, Copyright © 1987 by Society for Molecular Biology and Evolution
DR Nelson and HW Strobel
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).
ORIGINAL ARTICLE
Evolution of cytochrome P-450 proteins [published erratum appears in Mol Biol Evol 1988 Mar;5(2):199]
Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston 77225.
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