Patterns of selection across gene regulatory networks

McDonald, Jeanne M. C.; Reed, Robert D.

doi:10.1016/j.semcdb.2022.03.029

Cited by 8 publications

(4 citation statements)

References 94 publications

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“…The reigning genetic model for trait development involves the orchestrated expression of regulatory genes (such as transcription factors, coactivators, corepressors, and chromatin modifiers) that interact with the cis -regulatory elements (CREs) of their direct target genes. These interactions culminate in the expression of the realizator genes whose encoded RNAs and proteins make the characteristic phenotype [ 1 – 3 ]. These genes and their expression-controlling CREs embody a gene regulatory network (GRN).…”

Section: Introductionmentioning

confidence: 99%

A novel role for trithorax in the gene regulatory network for a rapidly evolving fruit fly pigmentation trait

et al. 2023

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Animal traits develop through the expression and action of numerous regulatory and realizator genes that comprise a gene regulatory network (GRN). For each GRN, its underlying patterns of gene expression are controlled by cis-regulatory elements (CREs) that bind activating and repressing transcription factors. These interactions drive cell-type and developmental stage-specific transcriptional activation or repression. Most GRNs remain incompletely mapped, and a major barrier to this daunting task is CRE identification. Here, we used an in silico method to identify predicted CREs (pCREs) that comprise the GRN which governs sex-specific pigmentation of Drosophila melanogaster. Through in vivo assays, we demonstrate that many pCREs activate expression in the correct cell-type and developmental stage. We employed genome editing to demonstrate that two CREs control the pupal abdomen expression of trithorax, whose function is required for the dimorphic phenotype. Surprisingly, trithorax had no detectable effect on this GRN’s key trans-regulators, but shapes the sex-specific expression of two realizator genes. Comparison of sequences orthologous to these CREs supports an evolutionary scenario where these trithorax CREs predated the origin of the dimorphic trait. Collectively, this study demonstrates how in silico approaches can shed novel insights on the GRN basis for a trait’s development and evolution.

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Section: Introductionmentioning

confidence: 99%

A novel role for trithorax in the gene regulatory network for a rapidly evolving fruit fly pigmentation trait

et al. 2023

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“…Key to this is understanding the evolution of gene regulatory networks (GRNs), control circuits common throughout the domains of life that determine the magnitude and timing of gene expression [4] in response to environmental and internal signals [5,6]. GRNs are frequent sites of adaptive mutation driving phenotypic evolution [7][8][9] and often underscore adaptation to-and survival in-new and changeable environments [10][11][12][13]. Alterations to GRNs can also enhance drug resistance and stress responses in the face of environmental challenges [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Evolutionary innovation through transcription factor rewiring in microbes is shaped by levels of transcription factor activity, expression, and existing connectivity

Shepherd,

Pierce,

Taylor

2023

PLoS Biol

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The survival of a population during environmental shifts depends on whether the rate of phenotypic adaptation keeps up with the rate of changing conditions. A common way to achieve this is via change to gene regulatory network (GRN) connections—known as rewiring—that facilitate novel interactions and innovation of transcription factors. To understand the success of rapidly adapting organisms, we therefore need to determine the rules that create and constrain opportunities for GRN rewiring. Here, using an experimental microbial model system with the soil bacterium Pseudomonas fluorescens, we reveal a hierarchy among transcription factors that are rewired to rescue lost function, with alternative rewiring pathways only unmasked after the preferred pathway is eliminated. We identify 3 key properties—high activation, high expression, and preexisting low-level affinity for novel target genes—that facilitate transcription factor innovation. Ease of acquiring these properties is constrained by preexisting GRN architecture, which was overcome in our experimental system by both targeted and global network alterations. This work reveals the key properties that determine transcription factor evolvability, and as such, the evolution of GRNs.

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“…Key to this is understanding the evolution of gene regulatory networks (GRNs), control circuits common throughout the domains of life that determine the magnitude and timing of gene expression 4 in response to environmental and internal signals 5,6 . GRNs are frequent sites of adaptive mutation driving phenotypic evolution 7–9 , and often underscore adaptation to - and survival in - new and changeable environments 10–13 . Determining how these networks evolve and identifying rules governing when and how a regulatory circuit adapts will allow us to better understand their role in determining the evolutionary success of an organism.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary innovation through transcription factor promiscuity in microbes is constrained by pre-existing gene regulatory network architecture

Shepherd

Pierce

Taylor

2022

Preprint

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The survival of a population during environmental shifts depends on whether the rate of phenotypic adaptation keeps up with the rate of changing conditions. A common way to achieve this is via change to gene regulatory network (GRN) connections conferring novel interactions on transcription factors. To understand the success of rapidly adapting organisms, we therefore need to determine the rules that create and constrain opportunities for GRN innovation. Here, using an experimental microbial model system we construct a maladapted GRN, through deletion of a master transcription factor, and challenge evolution to fix this network. We identify three key properties - high activation, high expression, and pre-existing low-level affinity for novel target genes - that facilitate transcription factor innovation via gain of functional promiscuity. Ease of acquiring these properties is constrained by pre-existing GRN architecture, which was overcome in our experimental system by both targeted and global network alterations. This work reveals the key properties that determine transcription factor evolvability, and as such, the evolution of GRNs.

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Patterns of selection across gene regulatory networks

Cited by 8 publications

References 94 publications

A novel role for trithorax in the gene regulatory network for a rapidly evolving fruit fly pigmentation trait

A novel role for trithorax in the gene regulatory network for a rapidly evolving fruit fly pigmentation trait

Evolutionary innovation through transcription factor rewiring in microbes is shaped by levels of transcription factor activity, expression, and existing connectivity

Evolutionary innovation through transcription factor promiscuity in microbes is constrained by pre-existing gene regulatory network architecture

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