A mechanistic basis for genetic assimilation in natural fly populations

Genetic assimilation is a process by which a trait originally driven by the environment becomes independent of the initial cue and is expressed constitutively in a population. More than seven decades have passed since Waddington's pioneering demonstration of the acquisition of morphological traits through genetic assimilation, but the underlying mechanism remains unknown. Here, we address this gap by performing combined genomic analyses of Waddington's genetic assimilation experiments using the ectopic veins (EV) phenocopy in Drosophila as a model. Our study reveals the assimilation of EV in both outbred and inbred fly natural populations, despite their limited genetic diversity. We identified key changes in the expression of developmental genes and pinpointed selected alleles involved in EV assimilation. The assimilation of EV is mainly driven by the selection of regulatory alleles already present in the ancestral populations, including the downregulation of the receptor tyrosine kinase gene Cad96Ca by the insertion of a transposable element in its 3′ untranslated region. The genetic variation at this locus in the inbred population is maintained by a large chromosomal inversion. In outbred populations, the evolution of EV results from a polygenic response shaped by the selective environment. Our results support a model in which selection for multiple preexisting alleles in the ancestral population, rather than stress-induced genetic or epigenetic variation, drives the evolution of EV in natural fly populations.