ArticleGenome biology and evolution2015
Molecular evolution of the CYP2D subfamily in primates: purifying selection on substrate recognition sites without the frequent or long-tract gene conversion.
Article in Genome biology and evolution, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Unlocking Ethiopia's genomic landscape and its global significance: a call for inclusive genomics research.Human genomics · 2026Review
- Association Between CYP2D7 and TCF20 Polymorphisms and Coronary Heart Disease.Cardiovascular toxicology · 2024Article
- Relationships between Bitter Taste Receptor Gene Evolution, Diet, and Gene Repertoire in Primates.Genome biology and evolution · 2024Article
- Signatures of Co-evolution and Co-regulation in the CYP3A and CYP4F Genes in Humans.Genome biology and evolution · 2024Article
- Simple and Robust Detection ofPharmaceuticals (Basel, Switzerland) · 2022Article
- Complex gene expansion of theEcology and evolution · 2018Article
- Concurrent action of purifying selection and gene conversion results in extreme conservation of the major stress-inducible Hsp70 genes in mammals.Scientific reports · 2018Article
- Sequencing the CYP2D6 gene: from variant allele discovery to clinical pharmacogenetic testing.Pharmacogenomics · 2017Review
- Computational Identification of the Paralogs and Orthologs of Human Cytochrome P450 Superfamily and the Implication in Drug Discovery.International journal of molecular sciences · 2016Article
- Article
- Whole-Genome Identification, Phylogeny, and Evolution of the Cytochrome P450 Family 2 (CYP2) Subfamilies in Birds.Genome biology and evolution · 2016Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human cytochrome P450 (CYP) 2D6 gene is a member of the CYP2D gene subfamily, along with the CYP2D7P and CYP2D8P pseudogenes. Although the CYP2D6 enzyme has been studied extensively because of its clinical importance, the evolution of the CYP2D subfamily has not yet been fully understood. Therefore, the goal of this study was to reveal the evolutionary process of the human drug metabolic system. Here, we investigate molecular evolution of the CYP2D subfamily in primates by comparing 14 CYP2D sequences from humans to New World monkey genomes. Window analysis and statistical tests revealed that entire genomic sequences of paralogous genes were extensively homogenized by gene conversion during molecular evolution of CYP2D genes in primates. A neighbor-joining tree based on genomic sequences at the nonsubstrate recognition sites showed that CYP2D6 and CYP2D8 genes were clustered together due to gene conversion. In contrast, a phylogenetic tree using amino acid sequences at substrate recognition sites did not cluster the CYP2D6 and CYP2D8 genes, suggesting that the functional constraint on substrate specificity is one of the causes for purifying selection at the substrate recognition sites. Our 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 CYP2D coding sequences.
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