Evolutionary changes in transcription factor coding sequence quantitatively alter sensory organ development and function.

Animals are characterized by a set of highly conserved developmental regulators. Changes in the regulatory elements of these regulators are thought to constitute the major driver of morphological evolution. However, the role of coding sequence evolution remains unresolved. To address this question, we used the Atonal family of proneural transcription factors as a model. coding sequence was endogenously replaced with that of homologues () at key phylogenetic positions, non- proneural genes, and the closest homologue to ancestral proneural genes. and the ancestral-like coding sequences rescued sensory organ fate in mutants, in contrast to non-. Surprisingly, different ATH factors displayed different levels of proneural activity as reflected by the number and functionality of sense organs. This proneural potency gradient correlated directly with ATH protein stability, including in response to Notch signaling, independently of mRNA levels or codon usage. This establishes a distinct and ancient function for ATHs and demonstrates that coding sequence evolution can underlie quantitative variation in sensory development and function.