دورية أكاديمية
Signatures of Co-evolution and Co-regulation in the CYP3A and CYP4F Genes in Humans.
| العنوان: | Signatures of Co-evolution and Co-regulation in the CYP3A and CYP4F Genes in Humans. |
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| المؤلفون: | Richard-St-Hilaire A; Département de biochimie et médecine moléculaire, Université de Montréal, Montreal, QC, Canada.; Sainte-Justine Hospital, Research Center, Montreal, QC, Canada., Gamache I; Département de biochimie et médecine moléculaire, Université de Montréal, Montreal, QC, Canada.; Montreal Heart Institute, Research Center, Montreal, QC, Canada., Pelletier J; Département de biochimie et médecine moléculaire, Université de Montréal, Montreal, QC, Canada.; McGill CERC in Genomic Medicine, McGill University, Montreal, Canada., Grenier JC; Montreal Heart Institute, Research Center, Montreal, QC, Canada., Poujol R; Montreal Heart Institute, Research Center, Montreal, QC, Canada., Hussin JG; Montreal Heart Institute, Research Center, Montreal, QC, Canada.; Département de médecine, Université de Montréal, Montreal, QC, Canada.; Mila-Quebec AI institute, Montreal, QC, Canada. |
| المصدر: | Genome biology and evolution [Genome Biol Evol] 2024 Jan 05; Vol. 16 (1). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 101509707 Publication Model: Print Cited Medium: Internet ISSN: 1759-6653 (Electronic) Linking ISSN: 17596653 NLM ISO Abbreviation: Genome Biol Evol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, UK : Oxford University Press |
| مواضيع طبية MeSH: | Cytochrome P-450 CYP3A*/genetics , Cytochrome P-450 CYP3A*/metabolism , Hominidae*/metabolism, Animals ; Humans ; Cytochrome P-450 Enzyme System/genetics ; Polymorphism, Genetic ; Selection, Genetic |
| مستخلص: | Cytochromes P450 (CYP450) are hemoproteins generally involved in the detoxification of the body of xenobiotic molecules. They participate in the metabolism of many drugs and genetic polymorphisms in humans have been found to impact drug responses and metabolic functions. In this study, we investigate the genetic diversity of CYP450 genes. We found that two clusters, CYP3A and CYP4F, are notably differentiated across human populations with evidence for selective pressures acting on both clusters: we found signals of recent positive selection in CYP3A and CYP4F genes and signals of balancing selection in CYP4F genes. Furthermore, an extensive amount of unusual linkage disequilibrium is detected in this latter cluster, indicating co-evolution signatures among CYP4F genes. Several of the selective signals uncovered co-localize with expression quantitative trait loci (eQTL), which could suggest epistasis acting on co-regulation in these gene families. In particular, we detected a potential co-regulation event between CYP3A5 and CYP3A43, a gene whose function remains poorly characterized. We further identified a causal relationship between CYP3A5 expression and reticulocyte count through Mendelian randomization analyses, potentially involving a regulatory region displaying a selective signal specific to African populations. Our findings linking natural selection and gene expression in CYP3A and CYP4F subfamilies are of importance in understanding population differences in metabolism of nutrients and drugs. Competing Interests: Conflict of Interest No competing interest is declared. (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.) |
| معلومات مُعتمدة: | #40157 Canada Foundation for Innovation (CFI); Montreal Heart Institute Foundation; Canadian Institutes of Health Research (CIHR); Robert-Cedergren Bioinformatics Awardee; Fonds de Recherche du Québec en Santé (FRQS) |
| فهرسة مساهمة: | Keywords: Cytochromes P450; co-evolution; gene expression; linkage disequilibrium; population genetics |
| المشرفين على المادة: | EC 1.14.14.1 (Cytochrome P-450 CYP3A) 9035-51-2 (Cytochrome P-450 Enzyme System) |
| تواريخ الأحداث: | Date Created: 20240111 Date Completed: 20240214 Latest Revision: 20240705 |
| رمز التحديث: | 20240705 |
| مُعرف محوري في PubMed: | PMC10805436 |
| DOI: | 10.1093/gbe/evad236 |
| PMID: | 38207129 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1759-6653 |
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| DOI: | 10.1093/gbe/evad236 |