29 November 2022
Physicians often observe that their patients can react differently to the same medical treatment: for some patients, the drug will prove inefficient, whereas for others, it might provoke side effects, sometimes rather serious.
These differences in response to exogenous compounds are phenotypic differences that can be due to several factors, including genetic factors, potentially unevenly distributed among human populations.
Using a standardized protocol, we demonstrate significant variation among Ethiopians, Omanis, Greeks, and Czechs in six out of seven measured phenotypes linked to 70–80% of drugs commonly used in the clinic. Significant genetic associations are evidenced by GWAS for four of these phenotypes, but genome scans of selection fail to detect positive signals in the genetic loci identified.
We hypothesize that the results of our joint analysis of phenotypic and genomic diversity are best explained by diverse mechanisms, including phenotypic plasticity and possibly balancing selection, so as to cope with the wide spectrum of both endogenous and exogenous molecules that the organism has to metabolise, but do not appear to favor positive selection as an adaptation to specific chemical environments.
Genome Biology and Evolution, Volume 14, Issue 12, December 2022, evac167. https://doi.org/10.1093/gbe/evac167
