Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish

Jared V. Goldstone, Andrew G. McArthur, Akira Kubota, Juliano Zanette, Thiago Parente, Maria E. Jönsson, David Nelson, John J. Stegeman

Research output: Contribution to journalArticle

210 Citations (Scopus)

Abstract

Background: Increasing use of zebrafish in drug discovery and mechanistic toxicology demands knowledge of cytochrome P450 (CYP) gene regulation and function. CYP enzymes catalyze oxidative transformation leading to activation or inactivation of many endogenous and exogenous chemicals, with consequences for normal physiology and disease processes. Many CYPs potentially have roles in developmental specification, and many chemicals that cause developmental abnormalities are substrates for CYPs. Here we identify and annotate the full suite of CYP genes in zebrafish, compare these to the human CYP gene complement, and determine the expression of CYP genes during normal development.Results: Zebrafish have a total of 94 CYP genes, distributed among 18 gene families found also in mammals. There are 32 genes in CYP families 5 to 51, most of which are direct orthologs of human CYPs that are involved in endogenous functions including synthesis or inactivation of regulatory molecules. The high degree of sequence similarity suggests conservation of enzyme activities for these CYPs, confirmed in reports for some steroidogenic enzymes (e.g. CYP19, aromatase; CYP11A, P450scc; CYP17, steroid 17a-hydroxylase), and the CYP26 retinoic acid hydroxylases. Complexity is much greater in gene families 1, 2, and 3, which include CYPs prominent in metabolism of drugs and pollutants, as well as of endogenous substrates. There are orthologous relationships for some CYP1 s and some CYP3 s between zebrafish and human. In contrast, zebrafish have 47 CYP2 genes, compared to 16 in human, with only two (CYP2R1 and CYP2U1) recognized as orthologous based on sequence. Analysis of shared synteny identified CYP2 gene clusters evolutionarily related to mammalian CYP2 s, as well as unique clusters.Conclusions: Transcript profiling by microarray and quantitative PCR revealed that the majority of zebrafish CYP genes are expressed in embryos, with waves of expression of different sets of genes over the course of development. Transcripts of some CYP occur also in oocytes. The results provide a foundation for the use of zebrafish as a model in toxicological, pharmacological and chemical disease research.

Original languageEnglish (US)
Article number643
JournalBMC Genomics
Volume11
Issue number1
DOIs
StatePublished - Nov 18 2010

Fingerprint

Zebrafish
Cytochrome P-450 Enzyme System
Genes
Toxicology
Steroid Hydroxylases
Steroid 17-alpha-Hydroxylase
Synteny
Aromatase
Drug Discovery
Multigene Family
Mixed Function Oxygenases
Tretinoin
Oocytes
Mammals
Embryonic Structures
Pharmacology
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Genetics

Cite this

Goldstone, J. V., McArthur, A. G., Kubota, A., Zanette, J., Parente, T., Jönsson, M. E., ... Stegeman, J. J. (2010). Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish. BMC Genomics, 11(1), [643]. https://doi.org/10.1186/1471-2164-11-643

Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish. / Goldstone, Jared V.; McArthur, Andrew G.; Kubota, Akira; Zanette, Juliano; Parente, Thiago; Jönsson, Maria E.; Nelson, David; Stegeman, John J.

In: BMC Genomics, Vol. 11, No. 1, 643, 18.11.2010.

Research output: Contribution to journalArticle

Goldstone, JV, McArthur, AG, Kubota, A, Zanette, J, Parente, T, Jönsson, ME, Nelson, D & Stegeman, JJ 2010, 'Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish', BMC Genomics, vol. 11, no. 1, 643. https://doi.org/10.1186/1471-2164-11-643
Goldstone JV, McArthur AG, Kubota A, Zanette J, Parente T, Jönsson ME et al. Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish. BMC Genomics. 2010 Nov 18;11(1). 643. https://doi.org/10.1186/1471-2164-11-643
Goldstone, Jared V. ; McArthur, Andrew G. ; Kubota, Akira ; Zanette, Juliano ; Parente, Thiago ; Jönsson, Maria E. ; Nelson, David ; Stegeman, John J. / Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish. In: BMC Genomics. 2010 ; Vol. 11, No. 1.
@article{914750c0d346413dbd1dac80e4bdbeb7,
title = "Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish",
abstract = "Background: Increasing use of zebrafish in drug discovery and mechanistic toxicology demands knowledge of cytochrome P450 (CYP) gene regulation and function. CYP enzymes catalyze oxidative transformation leading to activation or inactivation of many endogenous and exogenous chemicals, with consequences for normal physiology and disease processes. Many CYPs potentially have roles in developmental specification, and many chemicals that cause developmental abnormalities are substrates for CYPs. Here we identify and annotate the full suite of CYP genes in zebrafish, compare these to the human CYP gene complement, and determine the expression of CYP genes during normal development.Results: Zebrafish have a total of 94 CYP genes, distributed among 18 gene families found also in mammals. There are 32 genes in CYP families 5 to 51, most of which are direct orthologs of human CYPs that are involved in endogenous functions including synthesis or inactivation of regulatory molecules. The high degree of sequence similarity suggests conservation of enzyme activities for these CYPs, confirmed in reports for some steroidogenic enzymes (e.g. CYP19, aromatase; CYP11A, P450scc; CYP17, steroid 17a-hydroxylase), and the CYP26 retinoic acid hydroxylases. Complexity is much greater in gene families 1, 2, and 3, which include CYPs prominent in metabolism of drugs and pollutants, as well as of endogenous substrates. There are orthologous relationships for some CYP1 s and some CYP3 s between zebrafish and human. In contrast, zebrafish have 47 CYP2 genes, compared to 16 in human, with only two (CYP2R1 and CYP2U1) recognized as orthologous based on sequence. Analysis of shared synteny identified CYP2 gene clusters evolutionarily related to mammalian CYP2 s, as well as unique clusters.Conclusions: Transcript profiling by microarray and quantitative PCR revealed that the majority of zebrafish CYP genes are expressed in embryos, with waves of expression of different sets of genes over the course of development. Transcripts of some CYP occur also in oocytes. The results provide a foundation for the use of zebrafish as a model in toxicological, pharmacological and chemical disease research.",
author = "Goldstone, {Jared V.} and McArthur, {Andrew G.} and Akira Kubota and Juliano Zanette and Thiago Parente and J{\"o}nsson, {Maria E.} and David Nelson and Stegeman, {John J.}",
year = "2010",
month = "11",
day = "18",
doi = "10.1186/1471-2164-11-643",
language = "English (US)",
volume = "11",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish

AU - Goldstone, Jared V.

AU - McArthur, Andrew G.

AU - Kubota, Akira

AU - Zanette, Juliano

AU - Parente, Thiago

AU - Jönsson, Maria E.

AU - Nelson, David

AU - Stegeman, John J.

PY - 2010/11/18

Y1 - 2010/11/18

N2 - Background: Increasing use of zebrafish in drug discovery and mechanistic toxicology demands knowledge of cytochrome P450 (CYP) gene regulation and function. CYP enzymes catalyze oxidative transformation leading to activation or inactivation of many endogenous and exogenous chemicals, with consequences for normal physiology and disease processes. Many CYPs potentially have roles in developmental specification, and many chemicals that cause developmental abnormalities are substrates for CYPs. Here we identify and annotate the full suite of CYP genes in zebrafish, compare these to the human CYP gene complement, and determine the expression of CYP genes during normal development.Results: Zebrafish have a total of 94 CYP genes, distributed among 18 gene families found also in mammals. There are 32 genes in CYP families 5 to 51, most of which are direct orthologs of human CYPs that are involved in endogenous functions including synthesis or inactivation of regulatory molecules. The high degree of sequence similarity suggests conservation of enzyme activities for these CYPs, confirmed in reports for some steroidogenic enzymes (e.g. CYP19, aromatase; CYP11A, P450scc; CYP17, steroid 17a-hydroxylase), and the CYP26 retinoic acid hydroxylases. Complexity is much greater in gene families 1, 2, and 3, which include CYPs prominent in metabolism of drugs and pollutants, as well as of endogenous substrates. There are orthologous relationships for some CYP1 s and some CYP3 s between zebrafish and human. In contrast, zebrafish have 47 CYP2 genes, compared to 16 in human, with only two (CYP2R1 and CYP2U1) recognized as orthologous based on sequence. Analysis of shared synteny identified CYP2 gene clusters evolutionarily related to mammalian CYP2 s, as well as unique clusters.Conclusions: Transcript profiling by microarray and quantitative PCR revealed that the majority of zebrafish CYP genes are expressed in embryos, with waves of expression of different sets of genes over the course of development. Transcripts of some CYP occur also in oocytes. The results provide a foundation for the use of zebrafish as a model in toxicological, pharmacological and chemical disease research.

AB - Background: Increasing use of zebrafish in drug discovery and mechanistic toxicology demands knowledge of cytochrome P450 (CYP) gene regulation and function. CYP enzymes catalyze oxidative transformation leading to activation or inactivation of many endogenous and exogenous chemicals, with consequences for normal physiology and disease processes. Many CYPs potentially have roles in developmental specification, and many chemicals that cause developmental abnormalities are substrates for CYPs. Here we identify and annotate the full suite of CYP genes in zebrafish, compare these to the human CYP gene complement, and determine the expression of CYP genes during normal development.Results: Zebrafish have a total of 94 CYP genes, distributed among 18 gene families found also in mammals. There are 32 genes in CYP families 5 to 51, most of which are direct orthologs of human CYPs that are involved in endogenous functions including synthesis or inactivation of regulatory molecules. The high degree of sequence similarity suggests conservation of enzyme activities for these CYPs, confirmed in reports for some steroidogenic enzymes (e.g. CYP19, aromatase; CYP11A, P450scc; CYP17, steroid 17a-hydroxylase), and the CYP26 retinoic acid hydroxylases. Complexity is much greater in gene families 1, 2, and 3, which include CYPs prominent in metabolism of drugs and pollutants, as well as of endogenous substrates. There are orthologous relationships for some CYP1 s and some CYP3 s between zebrafish and human. In contrast, zebrafish have 47 CYP2 genes, compared to 16 in human, with only two (CYP2R1 and CYP2U1) recognized as orthologous based on sequence. Analysis of shared synteny identified CYP2 gene clusters evolutionarily related to mammalian CYP2 s, as well as unique clusters.Conclusions: Transcript profiling by microarray and quantitative PCR revealed that the majority of zebrafish CYP genes are expressed in embryos, with waves of expression of different sets of genes over the course of development. Transcripts of some CYP occur also in oocytes. The results provide a foundation for the use of zebrafish as a model in toxicological, pharmacological and chemical disease research.

UR - http://www.scopus.com/inward/record.url?scp=78349237831&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78349237831&partnerID=8YFLogxK

U2 - 10.1186/1471-2164-11-643

DO - 10.1186/1471-2164-11-643

M3 - Article

C2 - 21087487

AN - SCOPUS:78349237831

VL - 11

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - 1

M1 - 643

ER -