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

Simon Weinberger,Bassem A Hassan,Talah Hassan,Joerg T Albert,Annelies Claeys,Duru Ozbay,Natalie De Geest,Matthew P Topping,Jiekun Yan,Ariane Ramaekers,Xiaoli He

doi:10.7554/elife.26402

Abstract

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.

Highlights

Animals share a toolkit of highly conserved genes governing key processes of development and homeostasis
By measuring mechanotransduction in the Johnston’s organ (JO), a cluster of chordotonal organs (ChOs) in the second antennal segment, as a quantitative test of sensory organ performance, we demonstrate that different atonal homologues (ATHs) rescue various aspects of JO functionality
The absence of ato endogenous sequence and lack of protein expression was confirmed for all viable KIs (Figure 1—figure supplement 1A and B). These results indicate that ATHs share functional properties that distinguish them from other proneural basic helix-loop-helix (bHLH) Transcription factors (TFs)

Summary

Introduction

Animals share a toolkit of highly conserved genes governing key processes of development and homeostasis. Differential deployment of these genes, caused by cis-regulatory sequence variation, is often considered to be the key driver of developmental evolution (Carroll, 2008; Rokas, 2008; Prud’homme et al, 2007; Wittkopp and Kalay, 2012; Wray, 2007). Coding sequence (CDS) changes could play an important role and the relative, or differential, contribution of cisregulatory versus CDS variation to developmental evolution is under debate (Cheatle Jarvela and Hinman, 2015; Hoekstra et al, 2007; Lynch and Wagner, 2008; Stern and Orgogozo, 2008)

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