Evolutionary Insights into Pharmacogenes

At the Forefront of Drug Metabolism Research

Pharmacogenomics stands as a cornerstone of personalized medicine, successfully unraveling the genetic underpinnings of drug responses and adverse reactions. At the Pharmacogenomic Centre Beaulieu-Saucier at the MHI, our research focus on the diversity of drug metabolizing enzymes (DMEs), which are crucial for optimizing drug therapy. We leverage our unique capabilities to type large clinical cohorts and explore genomic regions through bioinformatics, population genetics and machine learning.

Highlighting the CYP Gene Family

Our project on the Cytochrome P450 (CYP) gene family explores their evolutionary dynamics and their significant role in drug metabolism and precision medicine across species. These enzymes are vital for metabolizing a myriad of substances, and their rapid evolution has been instrumental in adapting to diverse environmental compounds. Our projects include:

  • Tracing Human Evolution : We analyze the interactions between various CYP genes and pseudogenes in humans, using population genetics to uncover the evolutionary pressures that have shaped these gene families.
  • Understanding Pseudogenes : Focusing on the annotation and expression of CYP pseudogenes, we utilize RNA-seq and proteomics to identify candidate pseudogenes for further study, enhancing our understanding of their roles in human populations.
  • Comparative Genomic Insights : Extending our research to other species, we employ phylogenetic methods to study the evolutionary trajectories of CYP genes in primates and plants.

Representative Publications

Richard-St-Hilaire A, Gamache I, Pelletier J, Grenier JC, Raphaël P, Hussin JG. Signatures of Co-evolution and Co-regulation in the CYP3A and CYP4F Genes in Humans, Genome Biology and Evolution

Legault MA, Barhdadi A, Gamache I, Lemaçon A, Lemieux Perreault LP, Grenier JC, Sylvestre MP, Hussin JG, Rhainds D, Tardif JC, Dubé MP. 2023. Study of effect modifiers of genetically predicted CETP reduction. Genetic Epidemiology

Gamache I, Legault MA, Grenier JC, Sanchez R, Rhéaume E, Asgari S, Barhdadi A, Feroz Zada Y, Trochet H, Luo Y, Lecca L, Murray M, Raychaudhuri S, Tardif JC, Dubé MP, Hussin JG*. 2021. A sex-specific evolutionary interaction between ADCY9 and CETP. eLife

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