Rainforest hunter-gatherers from Southeast Asia are characterized by specific morphological features including a particularly dark skin color (D), short stature (S), woolly hair (W), and the presence of steatopygia (S)-fat accumulation localized in the hips (DSWS phenotype). Based on earlier findings in the Andamanese population, we initially characterized signatures of adaptive natural selection surrounding the calcium-sensing receptor gene in Southeast Asian rainforest groups exhibiting the DSWS phenotype. We identified the R990G substitution (rs1042636) as a candidate adaptive variant for experimental investigation. Although the calcium-sensing receptor plays a critical role in calcium homeostasis by directly regulating parathyroid hormone secretion, it is expressed in various tissues and it is implicated in numerous biological functions. Previous works have also characterized the R990G substitution as an activating polymorphism of the calcium-sensing receptor associated with hypocalcemia. Therefore, we generated a knock-in mouse for this substitution and investigated organismal phenotypes that could have become adaptive in rainforest hunter-gatherers from Southeast Asia. Interestingly, we found that mice homozygous for the derived allele exhibit not only lower serum calcium concentrations but also increased body weight and fat accumulation, probably due to enhanced preadipocyte differentiation and impaired lipolysis resulting from calcium-sensing receptor activation mediated by R990G. We speculate that such distinct features in humans could have promoted the survival of hunter-gatherer groups during periods of nutritional stress under the demanding conditions of Southeast Asian tropical rainforests.