Retained duplications and deletions of CYP2C genes among primates.
Level 5 - mechanism / opinion, no new human data
Comparative genomics and phylogenetic modeling (Level 5 by design analogy, non-clinical scholarship).
PubMed 29631055 · doi:10.1016/j.ympev.2018.03.037
What was done
The authors conducted a comparative genomic and phylogenetic analysis of cytochrome P450 2C (CYP2C) subfamily genes across primate genomes, including cercopithecoids, platyrrhines, and hominoids. They mapped gene duplication and deletion events and tested for positive selection across codons, comparing evolutionary patterns with dietary profiles to evaluate the role of dietary toxins in shaping CYP2C evolution.
What was found
Primate CYP2C paralogs partitioned into three clades: CYP2C18, CYP2C9/CYP2C19, and CYP2C8/CYP2C20. CYP2C18 was independently lost in Nomascus leucogenys and the Panini genomes, showing no evidence of positive selection. CYP2C20 was retained in cercopithecoids but lost in platyrrhines and hominoids, with 9 codons showing signatures of positive selection. CYP2C19 duplicated in basal catarrhines to yield CYP2C9, with the ancestral locus retained solely in hominoids.
Why it matters
Understanding the evolutionary history of CYP2C genes clarifies how ancestral adaptations to plant dietary xenobiotics shaped drug-metabolizing enzymes responsible for processing more than 20% of modern clinical pharmaceuticals.
Limits
The study is an in silico comparative genomic analysis and does not report biochemical or functional assays of enzyme activity. The abstract does not specify the exact number of primate species or genomes analyzed, and connections between genetic changes and specific dietary toxins remain inferential.
Cited by
- supports The human liver produces cytochrome P450 enzymes that rapidly remove potentially toxic ingested plant chemicals.