Functional and evolutionary characteristics of human genes encoding cell surface receptors involved in the regulation of appetite

Appetite is an instinct that has been formed through evolution. Appetite promotes normal growth and development in humans. However, under conditions of food abundance, appetite can become excessive, posing significant health risks. In this study we have identified 80 human genes whose orthologs regulated food intake in model animal species. More than 80 % of these genes encode G-protein-coupled receptors and 29 % were found to be involved in developmental processes. Using phylostratigraphic age index (PAI), which specifies the evolutionary age of a gene, we found that this set of 80 genes contains an increased proportion of genes with the same phylostratigraphic age (PAI = 6, the stage of Vertebrata divergence) indicating the coordinated evolution of this group of genes. Using divergence index (DI), which indicates the type of selection to which the gene is subjected, we observed significant enrichment for genes with DI ≤ 0.25, i.e., those that are subject to strong stabilizing selection. The subgroup of genes having DI ≤ 0.25 included 45 genes and was enriched with genes that are associated with developmental processes. This finding supports the hypothesis that developmental disturbances generally impose strong constraints on viability due to purifying selection.