B9 Insulin Polymorphism in Primates: Structural and Evolutionary Implications

Insulin, a vital hormone regulating metabolism, has evolved under selective pressures tied to dietary variations across primate lineages. This investigation examines a key amino acid variation at position B9 in the insulin B-chain: proline (Pro) in Old World monkeys such as the rhesus macaque ( Macaca mulatta ) and serine (Ser) in hominids, including humans. Through a comparative review of publicly available sequence and structural data, this study tests the hypothesis that this Pro-to-Ser shift represents an adaptive modification enhancing insulin's kinetic properties to cope with the episodic high-sugar intake typical of great ape diets. Proline at B9 imposes conformational rigidity, potentially slowing hexamer-to-monomer transitions, whereas serine introduces flexibility and hydrogen-bonding capacity, facilitating quicker activation. These alterations align with hominid metabolic demands for rapid glucose control amid fruit-rich foraging. Findings illuminate evolutionary trajectories in primate physiology and offer principles for engineering insulin therapeutics with optimized onset profiles.