Developmental origins of novel gut morphology in frogs

Phenotypic variation is a prerequisite for evolution by natural selection, yet the processes that give rise to the novel morphologies upon which selection acts are poorly understood. We employed a chemical genetic screen to identify developmental changes capable of generating morphological variation as observed among extant species. Specifically, we assayed for small molecules capable of transforming the ancestral larval foregut of the herbivorous Xenopus laevis to resemble the derived foregut of the carnivorous Lepidobatrachus laevis . Appropriately, the small molecules that demonstrate this capacity modulate morphogenetic pathways involved in gut development, including retinoic acid (RA) signaling. Identical manipulations in a species more closely related to Lepidobatrachus , Ceratophrys cranwelli , yielded even more similar transformations, corroborating the relevance of RA signaling variation in interspecific morphological change. Finally, we were able to recover the ancestral gut phenotype in Lepidobatrachus by performing a reverse chemical manipulation to upregulate RA signaling, providing strong evidence that modifications to this specific pathway promoted the emergence of a lineage‐specific phenotypic novelty. Small molecule screening may be valuable for identifying developmental mechanisms that underlie ecologically and evolutionarily relevant phenotypic variation.