Abstract

The form that an animal takes during development is directed by gene regulatory networks (GRNs). Developmental GRNs interpret maternally deposited molecules and externally supplied signals to direct cell-fate decisions, which ultimately leads to the arrangements of organs and tissues in the organism. Genetically encoded modifications to these networks have generated the wide range of metazoan diversity that exists today. Most studies of GRN evolution focus on changes to cis-regulatory DNA, and it was historically theorized that changes to the transcription factors that bind to these cis-regulatory modules (CRMs) contribute to this process only rarely. A growing body of evidence suggests that changes to the coding regions of transcription factors play a much larger role in the evolution of developmental gene regulatory networks than originally imagined. Just as cis-regulatory changes make use of modular binding site composition and tissue-specific modules to avoid pleiotropy, transcription factor coding regions also predominantly evolve in ways that limit the context of functional effects. Here, we review the recent works that have led to this unexpected change in the field of Evolution and Development (Evo-Devo) and consider the implications these studies have had on our understanding of the evolution of developmental processes.

Highlights

  • Gene regulatory networks (GRNs) explain the gene expression states that direct a cell to establish a particular fate [1]

  • Many of the studies we have discussed in this review suggest interesting ways GRN evolution can occur via transcription factor change, but further study is still required in order to understand the full mechanism

  • As these experimental examples continue to increase, we will be able to decipher what impact these changes have on the wiring of their GRNs and how this might differ from cis-regulatory module (CRM) mutations

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Summary

Introduction

Gene regulatory networks (GRNs) explain the gene expression states that direct a cell to establish a particular fate [1]. Context-dependent use of domains Alternative splicing can evolve to produce lineage-specific variants of transcription factors in a modular way from the existing structural composition This is thought to be useful in the evolution of developmental GRNs because different variants can be limited to a particular tissue or developmental stage (reviewed in [23]). The authors suggest that the causative amino-acid changes most likely produced a conformational difference in the protein in the eutherian lineage that makes a pre-existing binding interface accessible to Foxo1a [95] These case studies highlight the previously underappreciated versatility of transcription factor coding region changes, in addition to offering a mechanism for limiting the context of the evolved transcription factor’s function. GRNs integrate both signaling pathways and transcription factors, and so alteration of the post-translational modifications that connect them offers an attractive way of modifying developmental GRNs

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