Morphological evolution repeatedly caused by mutations in signaling ligand genes

Abstract

What types of genetic changes underlie evolution? Secreted signalingmolecules (syn. ligands) can induce cells to switch states and thus largely contributeto the emergence of complex forms in multicellular organisms. It has been proposedthat morphological evolution should preferentially involve changes in developmentaltoolkit genes such as signaling pathway components or transcription factors.However, this hypothesis has never been formally confronted to the bulk ofaccumulated experimental evidence. Here we examine the importance of ligandcodinggenes for morphological evolution in animals. We use Gephebase (http://www.gephebase.org), a database of genotype-phenotype relationships for evolutionarychanges, and survey the genetic studies that mapped signaling genes ascausative loci of morphological variation. To date, 19 signaling genes represent20% of the cases where an animal morphological change has been mapped to a gene(80/391). This includes the signaling gene Agouti, which harbors multiplecis-regulatory alleles linked to color variation in vertebrates, contrasting with theeffects of coding variation in its target, the melanocortin receptor MC1R. Insticklebacks, genetic mapping approaches have identified 4 signaling genes out of14 loci associated with lake adaptations. Finally, in butterflies, a total of 18 allelicvariants of the WntA Wnt-family ligand cause color pattern adaptations related towing mimicry, both within and between species. We discuss possible hypothesesexplaining these cases of natural replication (genetic parallelism) and conclude thatsignaling ligand loci are an important source of sequence variation underlyingmorphological change in nature.