Genetic diversity and natural selection footprints of the glycine amidinotransferase gene in various human populations.

The glycine amidinotransferase gene (GATM) plays a vital role in energy metabolism in muscle tissues and is associated with multiple clinically important phenotypes. However, the genetic diversity of the GATM gene remains poorly understood within and between human populations. Here we analyzed the 1,000 Genomes Project data through population genetics approaches and observed significant genetic diversity across the GATM gene among various continental human populations. We observed considerable variations in GATM allele frequencies and haplotype composition among different populations. Substantial genetic differences were observed between East Asian and European populations (FST = 0.56). In addition, the frequency of a distinct major GATM haplotype in these groups was congruent with population-wide diversity at this locus. Furthermore, we identified GATM as the top differentiated gene compared to the other statin drug response-associated genes. Composite multiple analyses identified signatures of positive selection at the GATM locus, which was estimated to have occurred around 850 generations ago in European populations. As GATM catalyzes the key step of creatine biosynthesis involved in energy metabolism, we speculate that the European prehistorical demographic transition from hunter-gatherer to farming cultures was the driving force of selection that fulfilled creatine-based metabolic requirement of the populations.