Evolutionary changes in transcription factor coding sequence quantitatively alter sensory organ development and function
Abstract
'Toolkit' genes are highly conserved developmental regulators. While changes in their regulatory elements contribute to morphological evolution, the role of coding sequence (CDS) evolution remains unresolved. We used CDS-specific knock-ins of the proneural transcription factor Atonal homologs (ATHs) to address this question. Drosophila Atonal CDS was endogenously replaced with that of distant ATHs at key phylogenetic positions, non-ATH proneural genes, and the closest CDS to ancestral proneural genes. ATHs and the ancestral-like gene rescued sensory organ fate in atonal mutants, in contrast to non-ATHs. Surprisingly, different ATHs displayed a gradient of quantitative variation in proneural activity and 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 CDS evolution can underlie quantitative variation in sensory development and function.
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Vlaams Instituut voor Biotechnologie
- Simon Weinberger
- Jiekun Yan
- Annelies Claeys
- Natalie De Geest
- Duru Ozbay
- Bassem A Hassan
- Ariane Ramaekers
Fonds Wetenschappelijk Onderzoek
- Simon Weinberger
- Jiekun Yan
- Annelies Claeys
- Natalie De Geest
- Duru Ozbay
- Bassem A Hassan
- Ariane Ramaekers
BELSPO
- Simon Weinberger
- Jiekun Yan
- Annelies Claeys
- Natalie De Geest
- Duru Ozbay
- Bassem A Hassan
- Ariane Ramaekers
European Commission
- Simon Weinberger
- Bassem A Hassan
Human Frontier Science Program
- Matthew P Topping
- Talah Hassan
- Xiaoli He
- Joerg T Albert
Biotechnology and Biological Sciences Research Council
- Matthew P Topping
- Talah Hassan
- Xiaoli He
- Joerg T Albert
Paul G. Allen Family Foundation
- Bassem A Hassan
Einstein Stiftung Berlin
- Bassem A Hassan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Weinberger et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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