Overdominance effect of the bovine ghrelin receptor (GHSR1a)-DelR242 locus on growth in Japanese Shorthorn weaner bulls: heterozygote advantage in bull selection and molecular mechanisms

Ghrelin and the ghrelin receptor (GHSR1a) are involved in growth hormone secretion, food intake, and several other important functions. Ghrelin acts on GHSR1a and induces signal transduction via the Gαq subunit. In our previous study, we identified the <i>DelR242</i> (<i>3R</i>) allele, a truncated 3-arginine residue (3R) [major type: 4 arginine residues (4R)] of the third intracellular loop of GHSR1a, with a high frequency in Japanese Shorthorn bulls (0.43) but with a low frequency in other cattle breeds (0.00-0.09). To further investigate the reasons for the higher frequency of the <i>3R</i> allele, we performed several experiments. In this study, we found a significant sex difference in the frequency of the <i>3R</i> allele. Statistical analysis revealed a significant overdominance effect of the <i>DelR242</i> locus on growth in Japanese Shorthorn weaner bulls. However, additive/dominance/overdominance effects of the <i>3R</i> allele on carcass traits in adult steers and dams were not significant. The mode of the overdominance effect was estimated to be solely controlled by the single <i>DelR242</i> locus without any other linked loci using linkage disequilibrium analysis in <em>GHSR1a</em>. These results indicated that <i>4R/3R</i> heterozygotes had a selective advantage in weaner bulls because of their higher average daily gain than homozygotes. We discussed possible molecular mechanisms involved in the overdominance effect of the <i>DelR242</i> locus on these traits in weaner bulls using a structural model of the complex consisting of a GHSR1a dimer and Gαq.