Supplementary Material for: Glutamate-sensing genes are conserved among populations compared to glutamate metabolism genes

Introduction: Glutamate is a representative taste molecule with an umami flavor and is a major nutrient found abundantly in nature. Furthermore, it plays a significant role in the human body as a key metabolic intermediate and neurotransmitter. Therefore, the divergence of glutamate functions among populations during their evolution is of particular interest with a hypothesis that the genetic variation can lead to understanding divergence in taste perception. To elucidate variation in glutamate applications and to deepen our understanding of taste perception, we examined the nucleotide diversity of genes associated with glutamate sensing and metabolism among human populations. Methods: We first established 67 genes related to glutamate sensing and metabolism based on the database and literature survey. Then, for those genes, we used a population genomics approach based on ten populations over 76,156 human genomes in the gnomAD database. Results: Statistical tests of means and medians of the minor allele frequencies did not show any significant difference among populations. However, we observed substantial differences between two functional groups, glutamate sensing and glutamate metabolism, in populations of Latino/admixed American, Ashkenazi Jewish, and Others. Interestingly, we could find significant differences between the African population and the East Asian population at the single nucleotide polymorphism level of glutamate metabolism genes, but no clear differences were noted in glutamate-sensing genes. These suggest that glutamate-sensing genes are under the functional constraint compared to glutamate metabolism genes. Conclusion: Thus, glutamate-sensing genes and metabolism genes have a contrasting mode of the evolution, and glutamate-sensing genes are conservatively evolved, indicating its functional importance.