SOT 2009 - Cytochrome P450 genes in zebrafish development

Cytochrome P450 genes in zebrafish development.
Goldstone, J., M. Jonsson, T. Parente, J. Zanette, A.G. McArthur, B.R. Woodin, D.R. Nelson, & J.J. Stegeman. 2009.
Presentation at the Society of Toxicology 48th Annual Meeting, Baltimore, Maryland.


This presentation summarizes observations on the full complement of CYP genes in zebrafish, a non-mammalian model for pharmacological, toxicological and carcinogenesis research. A total of 88 CYP genes were identified in zebrafish. Homologies between zebrafish and human CYP were inferred from amino acid sequence identity and molecular phylogeny. Functions and regulation of most zebrafish CYP are not known. For CYP that are likely involved principally in endogenous functions there is clear orthology between human genes and their zebrafish counterparts, although there are differences in numbers of genes in some families. Relative to the human CYP complement there is expansion or enhanced diversity in zebrafish CYP families 1, 2 and 3 thought to be most involved in xenobiotic metabolism. There are five CYP1 genes, five CYP3s, and 42 CYP2s in 11 subfamilies. Only two of the zebrafish CYP2s (CYP2R and CYP2U) warrant the same designation as in humans based on sequence identity. However, syntenic analysis reveals that there are some 11 genes in the zebrafish CYP2N, 2P, 2V, and 2AD subfamilies, all of which occur in tandem in a cluster that has shared synteny with the single human CYP2J2, indicating orthology. Studies of CYP2Ns and CYP2Ps in other species indicate functional similarity with human CYP2J2. The multiple CYP2Ks share synteny with CYP2W, but the CYP2Xs and CYP2AAs do not obviously share synteny with any human CYP2 genes. The five zebrafish CYP1s occur in four subfamilies, divided into 2 clades. Zebrafish CYP1s show organ, cell and developmental stage differences in transcript expression and in inducibility by aryl hydrocarbon receptor agonists. CYP1D1, which is most closely related to CYP1A, is distinctly not induced by AH receptor agonists. Oligonucleotide microarrays targeted to all zebrafish CYPs reveal that many CYPs, including 17 CYP2s, are expressed during early zebrafish development.