Evolution of cytochrome P-450 proteins

David Nelson, H. W. Strobel

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

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 occured ~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 >1,360 Mybp. The fourth gene duplication (~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 linage. The first occurred ~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 languageEnglish (US)
Pages (from-to)572-593
Number of pages22
JournalMolecular Biology and Evolution
Volume4
Issue number6
StatePublished - 1987
Externally publishedYes

Fingerprint

Gene Duplication
gene duplication
cytochrome P-450
Cytochrome P-450 Enzyme System
cytochrome
Genes
protein
gene
Proteins
drug
proteins
Cholesterol
cholesterol
drugs
Detoxification
phenobarbital
Mitochondria
Mammals
Methylcholanthrene
Birds

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences (miscellaneous)
  • Ecology, Evolution, Behavior and Systematics
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Genetics
  • Molecular Biology
  • Genetics(clinical)

Cite this

Evolution of cytochrome P-450 proteins. / Nelson, David; Strobel, H. W.

In: Molecular Biology and Evolution, Vol. 4, No. 6, 1987, p. 572-593.

Research output: Contribution to journalArticle

Nelson, D & Strobel, HW 1987, 'Evolution of cytochrome P-450 proteins', Molecular Biology and Evolution, vol. 4, no. 6, pp. 572-593.
Nelson, David ; Strobel, H. W. / Evolution of cytochrome P-450 proteins. In: Molecular Biology and Evolution. 1987 ; Vol. 4, No. 6. pp. 572-593.
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