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Macaque cytochromes P450: nomenclature, transcript, gene, genomic structure, and function.

Yasuhiro Uno¹, Kazuhide Iwasaki, Hiroshi Yamazaki

¹Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Kainan, Japan. uno-yasuhiro@snbl.co.jp

Drug Metabolism Reviews

|February 10, 2011

Summary

This review proposes a new nomenclature for monkey cytochrome P450 (CYP) genes, aligning them with human orthologs. This revised naming system enhances the utility of macaque models in crucial drug metabolism studies.

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Area of Science:

Pharmacogenomics
Comparative Genomics
Drug Metabolism Research

Background:

Monkeys, particularly macaques, are vital models in drug metabolism studies due to human evolutionary proximity.
Numerous cytochrome P450 (P450 or CYP) cDNAs have been identified in macaques.
Recent genomic analyses indicate some macaque P450s are orthologous to human P450s, necessitating nomenclature updates.

Purpose of the Study:

To review and propose a revised nomenclature for cytochrome P450 (P450 or CYP) genes in cynomolgus and rhesus monkeys.
To establish orthologous relationships between macaque and human P450s based on genomic and sequence data.
To enhance the understanding and application of macaque models in drug metabolism research.

Main Methods:

Comparative analysis of genomic structures of macaque, human, and rat P450 genes (CYP1-4 families).
Phylogenetic analysis and sequence identity comparisons to determine orthologous relationships.
Review of identified P450 cDNAs and their functional characteristics in various primate species.

Main Results:

Identified and proposed revised nomenclature for several macaque P450s, linking them to their human orthologs (e.g., CYP2B17/30 to CYP2B6, CYP3A8/21/64 to CYP3A4).
Established orthologous relationships based on sequence identity, phylogeny, and genomic organization.
Included data on Japanese monkeys, African green monkeys, and marmosets for broader comparative insights.

Conclusions:

The proposed revised nomenclature facilitates a clearer understanding of macaque P450 genes through comparative genomics.
This updated nomenclature is expected to improve the accuracy and feasibility of using macaque models in drug metabolism studies.
Aligning macaque P450 nomenclature with human orthologs strengthens their predictive value in preclinical drug development.