Changes throughout a Genetic Network Mask the Contribution of Hox Gene Evolution

Hox genes pattern the anterior-posterior axis of animals and are posited to drive animal body plan evolution, yet their precise role in evolution has been difficult to determine. Here, we identified evolutionary modifications in the Hox gene Abd-B that dramatically altered its expression along the body plan of Drosophila santomea. Abd-B is required for pigmentation in Drosophila yakuba, the sister species of D. santomea, and changes to Abd-B expression would be predicted to make large contributions to the loss of body pigmentation in D. santomea. However, manipulating Abd-B expression in current-day D. santomea does not affect pigmentation. We attribute this epistatic interaction to four other genes within the D. santomea pigmentation network, three of which have evolved expression patterns that do not respond to Abd-B. Our results demonstrate how body plans may evolve through small evolutionary steps distributed throughout Hox-regulated networks. Polygenicity and epistasis may hinder efforts to identify genes and mechanisms underlying macroevolutionary traits. [Display omitted] •Expression changes in a Hox gene correlate with loss of pigmentation in D. santomea•Restoring Hox expression to D. santomea does not restore pigmentation phenotype•Changes throughout a downstream Hox-regulated network mask effects of Hox evolution•Hox-regulated traits evolve by small steps distributed throughout entire networks Liu et al. identify five genes that have evolved regulatory mutations during the loss of pigmentation in Drosophila santomea. While changes they find in the Hox gene Abd-B would be predicted to have substantial effects on phenotype, they show that modifications throughout its downstream network epistatically mask the effects of Hox gene evolution.