Comparative genomics of insect peptide hormones: from annotation artifacts to evolutionary prediction

Insect peptide hormones are central signalling molecules that govern development, metabolism, reproduction and behaviour. Large-scale sequencing efforts have pushed the number of high-quality insect genomes into the hundreds, yet peptide precursor genes are particularly prone to pseudo-loss annotation because the open reading frames encoding mature peptides are extremely short and the mature peptide regions show low sequence conservation. Here we first review how recent methodological advances have uncovered and corrected such spurious gene losses, and we propose an asymmetric framework of evidentiary confidence in which gene presence and gene loss are evaluated against distinct standards. Re-examining the variation landscape of peptide genes after this calibration reveals that both losses and expansions are distributed non-randomly and are tightly linked to life history. On this basis we put forward a neuropeptide co-evolution hypothesis, which holds that major ecological niche transitions, through constraint-release dynamics, jointly drive neuropeptide gene loss, copy-number expansion, remodelling of precursor processing and functional reshaping, and provides a testable framework that moves comparative genomics from phenomenological description toward mechanistic prediction.