  Ecdysteroid hormones are major regulators in reproduction and development of
insects, including larval molts and metamorphosis. The functional ecdysone
receptor is a heterodimer of ECR (NR1H1) and USP-RXR (NR2B4), which is the
orthologue of vertebrate retinoid X receptors (RXR alpha, beta, gamma). Both
proteins belong to the superfamily of nuclear hormone receptors,
ligand-dependent transcription factors that share two conserved domains: the
DNA-binding domain (DBD) and the ligand-binding domain (LBD). In order to gain
further insight into the evolution of metamorphosis and gene regulation by
ecdysone in arthropods, we performed a phylogenetic analysis of both partners
of the heterodimer ECR/USP-RXR. Overall, 38 USP-RXR and 19 ECR protein
sequences, from 33 species, have been used for this analysis. Interestingly,
sequence alignments and structural comparisons reveal high divergence rates,
for both ECR and USP-RXR, specifically among Diptera and Lepidoptera. The most
impressive differences affect the ligand-binding domain of USP-RXR. In
addition, ECR sequences show variability in other domains, namely the
DNA-binding and the carboxy-terminal F domains. Our data provide the first
evidence that ECR and USP-RXR may have coevolved during holometabolous insect
diversification, leading to a functional divergence of the ecdysone receptor.
These results have general implications on fundamental aspects of insect
development, evolution of nuclear receptors, and the design of specific
insecticides.
