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Since the time of Darwin, biologists have sought to understand the origins and maintenance of life's diversity of form. However, the nature of the exact DNA mutations and molecular mechanisms that result in morphological differences between species remains unclear. Here, we characterize a nonsynonymous mutation in a transcriptional coactivator, limb bud and heart homolog (lbh), which is associated with adaptive variation in the lower jaw of cichlid fishes. Using both zebrafish and Xenopus, we demonstrate that lbh mediates migration of cranial neural crest cells, the cellular source of the craniofacial skeleton. A single amino acid change that is alternatively fixed in cichlids with differing facial morphologies results in discrete shifts in migration patterns of this multipotent cell type that are consistent with both embryological and adult craniofacial phenotypes. Among animals, this polymorphism in lbh represents a rare example of a coding change that is associated with continuous morphological variation. This work offers novel insights into the development and evolution of the craniofacial skeleton, underscores the evolutionary potential of neural crest cells, and extends our understanding of the genetic nature of mutations that underlie divergence in complex phenotypes.

A Nonsynonymous Mutation in the Transcriptional Regulator lbh Is Associated with Cichlid Craniofacial Adaptation and Neural Crest Cell Development