Distinct Molecular Strategies for Hox-Mediated Limb Suppression in Drosophila: From Cooperativity to Dispensability/Antagonism in TALE Partnership

摘要

The emergence following gene duplication of a large repertoire of Hox paralogue proteins underlies the importance taken by Hox proteins in controlling animal body plans in development and evolution. Sequence divergence of paralogous proteins accounts for functional specialization, promoting axial morphological diversification in bilaterian animals. Yet functionally specialized paralogous Hox proteins also continue performing ancient common functions. In this study, we investigate how highly divergent Hox proteins perform an identical function. This was achieved by comparing in Drosophila the mode of limb suppression by the central (Ultrabithorax and AbdominalA) and posterior class (AbdominalB) Hox proteins. Results highlight that Hox-mediated limb suppression relies on distinct modes of DNA binding and a distinct use of TALE cofactors. Control of common functions by divergent Hox proteins, at least in the case studied, relies on evolving novel molecular properties. Thus, changes in protein sequences not only provide the driving force for functional specialization of Hox paralogue proteins, but also provide means to perform common ancient functions in distinct ways. Author Summary Animal body plan diversity is controlled by transcription factors that select within each cell of a multi-cellular organism the set of genes to be expressed, eventually allowing distinct fate to emerge according to spatial coordinates. Transcription factors can be grouped based on their DNA binding domains in a few classes that likely arise from a common ancestral protein. This raises the question of how, within each class, transcription factors have gained specific function, and while doing so how they still continue performing ancient functions. Hox proteins, which play key roles in diversifying animal morphology, have largely been used to unravel the mechanisms underlying functional diversification of transcription factors. Here we use this family of transcription factors to investigate how common functions are achieved by divergent transcription factors. Results suggest that changes in protein sequences not only provide the driving force for defining novel and specific functions, but also provide means to perform common ancient functions in distinct ways.