Abstract
Hox genes play a fundamental role in regulating the embryonic development of all animals. Manipulation of these transcription factors in model organisms has unraveled key aspects of evolution, like the transition from fin to limb. However, by virtue of their fundamental role and pleiotropic effects, simultaneous knockouts of several of these genes pose significant challenges. Here, we report on evolutionary simplification in two species of the dwarf minnow genus Paedocypris using whole genome sequencing. The two species feature unprecedented Hox gene loss and genome reduction in association with their massive developmental truncation. We also show how other genes involved in the development of musculature, nervous system, and skeleton have been lost in Paedocypris, mirroring its highly progenetic phenotype. Further, we identify two mechanisms responsible for genome streamlining: severe intron shortening and reduced repeat content. As a naturally simplified system closely related to zebrafish, Paedocypris provides novel insights into vertebrate development.