Everything you wanted to know about the evolution of insect Insulin receptors but were afraid to ask

Photo description: (A) Schematic summary of major insulin receptor gene duplications (highlighted in blue) and two independent tyrosine kinase losses (in red) leading to decoys of insulin receptors. (B) 3D structure of insulin receptor and DR2 dimers based on homology modeling. (C) Schematic depiction of major protein domains in insulin receptor and insulin receptor-derived DR2 and SDR.

To broad public, the insulin/insulin-like growth factor signaling (IIS) is mostly known for its involvement in diabetes mellitus. However, IIS is a conserved regulatory pathway ubiquitous in Metazoa and found, for example, even in Porifera. In this study, we present a comprehensive phylogenetic analysis of insect InR sequences in 118 species from 23 orders. We identified two gene clusters (Cluster I and II) resulting from an ancestral duplication in a late ancestor of winged insects, which remained conserved in most lineages, only in some of them being subject to further duplications or losses. One remarkable yet neglected feature of InR evolution is the loss of the tyrosine kinase catalytic domain, responsible for canonical signal transduction, giving rise to decoys of insulin receptors in both clusters. Within the Cluster I, we confirmed the presence of the secreted decoy of insulin receptor (SDR) in all studied Muscomorpha (order Diptera). More importantly, we described a new tyrosine kinase-less gene (DR2) in the Cluster II, conserved in apical Holometabola for circa 300 million years. We further experimentally investigated the role of IIS in the linden bug, Pyrrhocoris apterus, in wing polymorphism control. We differentially silenced the three P. apterus InRs and confirmed their participation in wing polymorphism control. We observed a pattern of Cluster I and II InRs impact on wing development, which differed from that postulated in planthoppers, suggesting an independent establishment of IIS control over wing development, leading to differences in the cooption of multiple InRs in wing polyphenism control in different taxa.

Smýkal V., Pivarči M., Provazník J., Bazalová O., Jedlička P., Lukšan O., Horák A., Vaněčková H., Beneš V., Fiala I., Hanus R., Doležel D. (2020) Complex evolution of insect insulin receptors and homologous decoy receptors, and functional significance of their multiplicity. Molecular Biology and Evolution, in press, Published online 26 February 2020, msaa048, doi:org/10.1093/molbev/msaa048