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Metazoan cytochrome P450 evolution

D R Nelson1

  • 1Department of Biochemistry, University of Tennessee, Memphis 38163, USA. dnelson@utmem1.utmem.edu

Comparative Biochemistry and Physiology. Part C, Pharmacology, Toxicology & Endocrinology
|February 11, 1999
PubMed
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Cytochrome P450 (P450) families are grouped into P450 CLANS. Mammalian and insect P450 families share a clan, and all mitochondrial P450s appear to form a single clan.

Area of Science:

  • Biochemistry
  • Evolutionary Biology
  • Genomics

Background:

  • Cytochrome P450 (P450) enzymes are crucial for diverse biological processes.
  • 37 P450 families are currently identified across animal species.
  • Understanding P450 evolution and classification is essential for comparative genomics.

Purpose of the Study:

  • Introduce the concept of P450 CLANS (higher-order groupings of P450 families).
  • Investigate the evolutionary relationships and clan memberships of P450 families across different taxa.
  • Explore the origins of mitochondrial P450s and their evolutionary trajectories.

Main Methods:

  • Comparative analysis of P450 gene families across various animal phyla.
  • Phylogenetic reconstruction to infer evolutionary relationships.

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  • Identification of conserved P450 clans and their ancestral origins.

    • Main Results:

    • Mammalian CYP3 and CYP5 families are grouped in the same clan as insect CYP6 and CYP9.
    • All identified mitochondrial P450s belong to a single P450 clan.
    • Evidence suggests mitochondrial P450s arose from mistargeted microsomal P450s post-coelomate divergence.
    • Distinct P450 clusters indicate independent recruitment of ancestral P450s for expansion in major taxa.
    • Insects expanded from the CYP4 family ancestor, while vertebrates and C. elegans utilized a common ancestor for distinct P450 family expansions.

    Conclusions:

    • The P450 CLAN concept provides a framework for higher-order classification of P450 superfamilies.
    • Mitochondrial P450 evolution is linked to gene mistargeting events.
    • Taxon-specific P450 expansions highlight diverse evolutionary strategies in response to environmental pressures.