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Under-dominance constrains the evolution of negative autoregulation in diploids

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Date
21/03/2013
Author
Stewart, Alexander J
Seymour, Robert M
Pomiankowski, Andrew
Reuter, Max
Keywords
Animals
Binding Sites
Diploidy
Drosophila melanogaster
Escherichia coli/genetics
Evolution, Molecular
Gene Expression Regulation
Gene Regulatory Networks
Homeostasis
Humans
Models, Genetic
Molecular Dynamics Simulation
Monte Carlo Method
Mutation
Saccharomyces cerevisiae/genetics
Transcription Factors/genetics
QH426 Genetics
QR Microbiology
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Abstract
Regulatory networks have evolved to allow gene expression to rapidly track changes in the environment as well as to buffer perturbations and maintain cellular homeostasis in the absence of change. Theoretical work and empirical investigation in Escherichia coli have shown that negative autoregulation confers both rapid response times and reduced intrinsic noise, which is reflected in the fact that almost half of Escherichia coli transcription factors are negatively autoregulated. However, negative autoregulation is rare amongst the transcription factors of Saccharomyces cerevisiae. This difference is surprising because E. coli and S. cerevisiae otherwise have similar profiles of network motifs. In this study we investigate regulatory interactions amongst the transcription factors of Drosophila melanogaster and humans, and show that they have a similar dearth of negative autoregulation to that seen in S. cerevisiae. We then present a model demonstrating that this striking difference in the noise reduction strategies used amongst species can be explained by constraints on the evolution of negative autoregulation in diploids. We show that regulatory interactions between pairs of homologous genes within the same cell can lead to under-dominance--mutations which result in stronger autoregulation, and decrease noise in homozygotes, paradoxically can cause increased noise in heterozygotes. This severely limits a diploid's ability to evolve negative autoregulation as a noise reduction mechanism. Our work offers a simple and general explanation for a previously unexplained difference between the regulatory architectures of E. coli and yeast, Drosophila and humans. It also demonstrates that the effects of diploidy in gene networks can have counter-intuitive consequences that may profoundly influence the course of evolution.
Citation
Stewart , A J , Seymour , R M , Pomiankowski , A & Reuter , M 2013 , ' Under-dominance constrains the evolution of negative autoregulation in diploids ' , PLoS Computational Biology , vol. 9 , no. 3 , e1002992 . https://doi.org/10.1371/journal.pcbi.1002992
Publication
PLoS Computational Biology
Status
Peer reviewed
DOI
https://doi.org/10.1371/journal.pcbi.1002992
ISSN
1553-734X
Type
Journal article
Rights
Copyright © 2013 Stewart et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/21494

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