Evolutionary changes in transcription factor coding sequence quantitatively alter sensory organ development and function
Simon Weinberger,
Matthew P Topping,
Jiekun Yan,
Annelies Claeys,
Natalie De Geest,
Duru Ozbay,
Talah Hassan,
Xiaoli He,
Joerg T Albert,
Bassem A Hassan,
Ariane Ramaekers
Affiliations
Simon Weinberger
VIB Center for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium; Program in Molecular and Developmental Genetics, Doctoral School for Biomedical Sciences, University of Leuven School Group Biomedicine, Leuven, Belgium
Matthew P Topping
Ear Institute, University College London, London, United Kingdom; Centre for Mathematics and Physics in the Life Sciences and Experimental Biology (CoMPLEX), University College London, London, United Kingdom
Jiekun Yan
VIB Center for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium
Annelies Claeys
VIB Center for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium
Natalie De Geest
VIB Center for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium
Duru Ozbay
VIB Center for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium
Talah Hassan
Ear Institute, University College London, London, United Kingdom
Xiaoli He
Ear Institute, University College London, London, United Kingdom
Joerg T Albert
Ear Institute, University College London, London, United Kingdom; Centre for Mathematics and Physics in the Life Sciences and Experimental Biology (CoMPLEX), University College London, London, United Kingdom; Department of Cell and Developmental Biology, University College London, London, United Kingdom
VIB Center for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium; Program in Molecular and Developmental Genetics, Doctoral School for Biomedical Sciences, University of Leuven School Group Biomedicine, Leuven, Belgium; Institut du Cerveau et de la Moelle Epinière (ICM) - Hôpital Pitié-Salpêtrière, UPMC, Sorbonne Universités, Inserm, CNRS, Paris, France
VIB Center for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium; Institut du Cerveau et de la Moelle Epinière (ICM) - Hôpital Pitié-Salpêtrière, UPMC, Sorbonne Universités, Inserm, CNRS, Paris, France
Animals are characterized by a set of highly conserved developmental regulators. Changes in the cis-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. Drosophila atonal coding sequence was endogenously replaced with that of atonal homologues (ATHs) at key phylogenetic positions, non-ATH proneural genes, and the closest homologue to ancestral proneural genes. ATHs and the ancestral-like coding sequences rescued sensory organ fate in atonal mutants, in contrast to non-ATHs. 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.
