Duplicated paralog of insulin receptor functions distinctively in locust reproduction for high fecundity

Insulin receptor (InR) mediates the highly conserved insulin/insulin-like growth factor signaling pathway that regulates a broad range of life-history traits. Most insects encode 2 InR paralogs, but their functional divergence and redundancy remain to be explored. Here, we pursued the functionality of 2 InRs, LmInR1, and LmInR2, in the migratory locust Locusta migratoria. LmInR1 is clustered into the clade of ancestral InR, and LmInR2 belongs to the clade of InR gene duplication. While LmInR1 expression was at the highest levels in nymphal stage and adult ovary, LmInR2 was predominantly expressed in adult fat body. Loss of LmInR1 function led to defective nymph-adult transition and reproduction. LmInR2 depletion had little effect on metamorphosis, but caused severe defects in female reproduction, including remarkable reduction of Vitellogenin (Vg) expression and arrested egg development. Interestingly, LmInR1 expression responded to lower levels of glucose, whereas LmInR2 was expressed in response to increasing concentrations of glucose. Moreover, the expression of LmInR2 but not LmInR1 was responsive to juvenile hormone (JH) and its receptor. The results suggest that LmInR2 has evolved neofunctionalization for massive Vg synthesis required for synchronous maturation of dozens of oocytes in a high-fecundity insect. This study reveals a novel aspect of differential functions of InR paralogs and provides new insights into understanding of the insulin signaling cascade in insects.