Molecular characteristics of IGF and IGF1R genes and their potential roles on longevity in two scallops with distinct lifespans

Abstract

Bay scallops are commercially important bivalve species for aquaculture worldwide, but the serious inbreeding depression is decreasing their production. Some interspecific hybrids of bay scallops (Argopecten irradians irradians) and Peruvian scallops (A. purpuratus) exhibit longer lifespan and significantly larger size for high yield, which may result from the longevity genes of Peruvian scallops. Insulin-like growth factor (IGF) system, as the conspicuous entry point of insulin/insulin-like growth factor signal (IIS) pathway, regulates various cellular processes including growth, autophagy, aging and longevity, but its roles remain unexplored in marine animals. In this study, we separately cloned a unique IGF2 (ApIGF2 and AiIGF2) and IGF1R (ApIGF1R and AiIGF1R) for the first time from two closely related Argopecten scallops with distinct lifespans and characterized for their ability to regulate longevity. Sequence analysis demonstrated that there were six-span transmembrane domains located at the additional extension of C-terminus special to AiIGF2, which appeared to relate to the differences in posttranslational processing. The amino acid variation (Y247) in TyrKc domain may be a key site affecting ApIGF1R kinase activity for longevity. Spatiotemporal expression of IGF2 and IGF1R during development and aging showed that the mantle and gonad are representative tissues for aging in scallops. The dietary restriction assay revealed the beneficial effects of attenuated IGF2 and IGF1R levels on longevity in scallops. The invigorated IGF1R conferred DNA repair and prosurvival properties to Peruvian scallops for radio-resistance after acute radioresistance. Inhibition of AiIGF1R upregulated the expression of senescence-associated genes (PENT, FoxO, CAT, Mn-SOD) and antioxidant enzyme activities, and suppressed the senescence marker β-GAL activity, indicating that IGF1R was a crucial regulator for longevity in scallops. Collectively, our work would bring us closer to understanding the longevity mechanism mediated by IGF system and breeding larger and long-lived hybrids for the sustainable development of aquaculture.