Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants.

  title={Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants.},
  author={David R. Nelson and Darryl C. Zeldin and Susan M. G. Hoffman and Lois J. Maltais and Hester M. Wain and Daniel W. Nebert},
  volume={14 1},
OBJECTIVES Completion of both the mouse and human genome sequences in the private and public sectors has prompted comparison between the two species at multiple levels. This review summarizes the cytochrome P450 (CYP) gene superfamily. For the first time, we have the ability to compare complete sets of CYP genes from two mammals. Use of the mouse as a model mammal, and as a surrogate for human biology, assumes reasonable similarity between the two. It is therefore of interest to catalog the… 

Computational Identification of the Paralogs and Orthologs of Human Cytochrome P450 Superfamily and the Implication in Drug Discovery

The results show that each human CYP has various numbers of paralogs and orthologs using GeneCards and Ensembl, which facilitate the understanding of the evolutionary relationships and functional implications of thehuman CYP superfamily in drug discovery.

Evolution of the CYP2D gene cluster in humans and four non-human primates.

The results indicate that CYP2D7P has been duplicated from CYP 2D6 before the divergence between humans and great apes, whereas CYp2D6 and CYP1D8P have been already present in the stem lineages of New World monkeys and Catarrhini.

Evolution of the CYP 2 D gene cluster in humans and four non-human primates

A preliminary study to investigate the evolution and gene organization of the CYP2D subfamily, focused on humans and four nonhuman primates, indicates that CYP1D7P has been duplicated from CYP3D6 before the divergence between humans and great apes and chimeric sequences in the chimpanzee genome appear to be exchanged.

Phylogenetic and Functional Analysis of the Vertebrate Cytochrome P450 2 Family

Analysis of site-specific evolution indicates that some substrate recognition sites (SRS) previously proposed for CYP genes do not have elevated rates of evolution, suggesting that these regions of the protein are not necessarily important in recognition of CYP2 substrates.

Molecular Evolution of the CYP2D Subfamily in Primates: Purifying Selection on Substrate Recognition Sites without the Frequent or Long-Tract Gene Conversion

The results suggest that the CYP2D gene subfamily in primates has evolved to maintain the regioselectivity for a substrate hydroxylation activity between individual enzymes, even though extensive gene conversion has occurred across CYP1D coding sequences.

Generation and Characterization of Novel Cytochrome P450 Cyp2c Gene Cluster Knockout and CYP2C9 Humanized Mouse Lines

To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, a mouse model with a deletion of the murine Cyp2C gene cluster and a corresponding humanized model expressing CYP 2C9 specifically in the liver are generated.

Characterization of Four New Mouse Cytochrome P450 Enzymes of the CYP2J Subfamily

It is concluded that the four new CYP2J isoforms might be involved in the metabolism of AA and LA to bioactive lipids in mouse hepatic and extrahepatic tissues.

Trans-chromosomic mice containing a human CYP3A cluster for prediction of xenobiotic metabolism in humans.

It is shown that the introduction of a human artificial chromosome (HAC) containing the entire genomic human CYP3A locus recapitulates tissue- and stage-specific expression of human CYp3A genes and xenobiotic metabolism in mice.

Deletion of 30 Murine Cytochrome P450 Genes Results In Viable Mice With Compromised Drug Metabolism

Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity.



Organization and evolution of the Cyp2 gene cluster on mouse chromosome 7, and comparison with the syntenic human cluster.

Part of the mouse and human gene clusters are similarly arranged, but the data indicate that a significantly different series of duplication events created the modern gene organizations in the two species.

Comparison of P450s from human and fugu: 420 million years of vertebrate P450 evolution.

  • D. Nelson
  • Biology
    Archives of biochemistry and biophysics
  • 2003

Organization and evolution of the cytochrome P450 CYP2A-2B-2F subfamily gene cluster on human chromosome 19

The identification of all genes and pseudogenes in this cluster makes it possible to determine the origins of some previously known variant P450 transcripts.

P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature.

This revision supersedes the four previous updates in which a nomenclature system, based on divergent evolution of the P450 superfamily has been described and is similar to that proposed in the previous updates.

Evolution of a highly polymorphic human cytochrome P450 gene cluster: CYP2D6.

Cytochrome P450 and the individuality of species.

  • D. Nelson
  • Biology
    Archives of biochemistry and biophysics
  • 1999
The biosynthesis of cholesterol in bacteria is discussed in relation to CYP51 as a lanosterol 14 alpha-demethylase, which may have been the first eukaryotic P450.

Isolation of CYP3A5P cDNA from human liver: a reflection of a novel cytochrome P-450 pseudogene.

Organization, structure and evolution of the CYP2 gene cluster on human chromosome 19.

This work comprehensively review the organization, structure, and expression of genes from all six subfamilies of the cytochrome P450 superfamily and presents a general hypothesis for the evolution of this complex gene cluster.