Integrative molecular characterization and in silico analyses of caprine MC3R, MC4R, and MC5R genes

The MC3R, MC4R, and MC5R genes have been linked to livestock production traits as well as obesity phenotypes in humans. However, the molecular characterization and association studies of these genes are scarce in goats. Thus, this study was carried out to understand the genetic variation in the form of SNPs and its consequential interaction of the respective protein with their agonist (alpha-MSH). In the present study, the caprine MC3R, MC4R and MC5R genes were molecularly characterized, in which two SNPs at c.C666T and c.G723A in the MC3R gene, three heterozygote SNPs at c.C57Y, c.C110M, and c.T360Y in the MC4R gene, and two SNPs at c.T181A and c. G473A (novel) in the MC5R gene were observed. The amino acid changes were observed in MC4R (A37D) and MC5R (p.F61I and p.R158H) proteins. In silico analyses such as prediction of primary, secondary, and tertiary structures of proteins, gene ontology, gene enrichment analysis, and pathway annotation were carried out for the respective genes. The mechanisms of the MC3R, MC4R and MC5R proteins involved in adult feeding behavior were revealed by pathway annotation. The docking studies revealed the interactions of the protein with the agonist (alpha-MSH). The interacting segment (His6, Phe7, Arg8, and Trp9) of alpha-MSH plays an important role in the selectivity of melanocortin receptors and the energy homeostasis pathway. Further, extensive studies are needed to find the association of SNPs to various production traits in goats.