Publication Detail

Evolutionary history and functional diversity of the cytochrome P450 1 gene family

John Stegeman, J. V. Goldstone, M. E. Jonsson, A. Kubota, B. Lemaire
2 pp.
MITSG 12-33
$5.50 DOM / $7.50 INT

The CYP1 gene family, a cornerstone in toxicological processes, has been implicated also in physiological processes. Here we summarize the history and current views of this gene family. CYP1As have long been known to participate in responses to AH receptor agonists and metabolism of carcinogens and other chemicals. CYP1B1 has regulatory and catalytic functions similar to the CYP1As. The CYP1Cs and CYP1D1, and the early deuterostome CYP1s, are much less well known. CYP1As and CYP1D1 form a single clade distinct from a CYP1B/CYP1C clade. All four subfamilies occur in teleost fish, amphibians, and lizards. However, the CYP1D line appears lost from birds, and the CYP1Cs are absent from mammals. Paralogous CYP1As occur in the mammals and birds and paralogous CYP1Cs in fish. The Coelacanth (Latimeria chalumnae) genome reveals a single CYP1C consistent with CYP1C duplication in the teleost line. Induction differs among the CYP1 genes, suggesting different functions. Patterns of basal expression are highly similar between species, suggesting that some CYP1s have conserved endogenous functions, although in fish the patterns of expression in early development (egg through mid-blastula transition) differ between species. Epigenetic mechanisms underlay differences in expression of mammalian CYP1As, but the basis for other differences are not known. Mammalian CYP1 functions are reasonably well known from expressed proteins and knockout mice. Analysis of CYP1 functions in non-mammalian species has lagged behind, although modeling and studies with expressed zebrafish CYP1s have begun to correct this. CYP1s have been proposed to function in feedback regulation of endogenous AHR ligands that may regulate cell proliferation. Determining this and other endogenous functions for CYP1s and CYP1-like genes in early diverging groups is an area rich with potential. (NIH R01ES015912 and P42ES007381 to JS, and Carl Tryggers Stiftelse and Swedish Research Council Formas to M.J.).

type: Presentations

Parent Project

Project No.: 2010-R/RCM-28
Title: Active samplers: development of biomarkers for coastal pollution in the blue mussel, Mytilus edulis