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RNA-mediated gene regulation is less evolvable than transcriptional regulation


Payne, Joshua L; Khalid, Fahad; Wagner, Andreas (2018). RNA-mediated gene regulation is less evolvable than transcriptional regulation. PNAS Proceedings of the National Academy of Sciences of the United States of America, 115(15):E3481-E3490.

Abstract

Much of gene regulation is carried out by proteins that bind DNA or RNA molecules at specific sequences. One class of such proteins is transcription factors, which bind short DNA sequences to regulate transcription. Another class is RNA binding proteins, which bind short RNA sequences to regulate RNA maturation, transport, and stability. Here, we study the robustness and evolvability of these regulatory mechanisms. To this end, we use experimental binding data from 172 human and fruit fly transcription factors and RNA binding proteins as well as human polymorphism data to study the evolution of binding sites in vivo. We find little difference between the robustness of regulatory protein–RNA interactions and transcription factor–DNA interactions to DNA mutations. In contrast, we find that RNA-mediated regulation is less evolvable than transcriptional regulation, because mutations are less likely to create interactions of an RNA molecule with a new RNA binding protein than they are to create interactions of a gene regulatory region with a new transcription factor. Our observations are consistent with the high level of conservation observed for interactions between RNA binding proteins and their target molecules as well as the evolutionary plasticity of regulatory regions bound by transcription factors. They may help explain why transcriptional regulation is implicated in many more evolutionary adaptations and innovations than RNA-mediated gene regulation.

Abstract

Much of gene regulation is carried out by proteins that bind DNA or RNA molecules at specific sequences. One class of such proteins is transcription factors, which bind short DNA sequences to regulate transcription. Another class is RNA binding proteins, which bind short RNA sequences to regulate RNA maturation, transport, and stability. Here, we study the robustness and evolvability of these regulatory mechanisms. To this end, we use experimental binding data from 172 human and fruit fly transcription factors and RNA binding proteins as well as human polymorphism data to study the evolution of binding sites in vivo. We find little difference between the robustness of regulatory protein–RNA interactions and transcription factor–DNA interactions to DNA mutations. In contrast, we find that RNA-mediated regulation is less evolvable than transcriptional regulation, because mutations are less likely to create interactions of an RNA molecule with a new RNA binding protein than they are to create interactions of a gene regulatory region with a new transcription factor. Our observations are consistent with the high level of conservation observed for interactions between RNA binding proteins and their target molecules as well as the evolutionary plasticity of regulatory regions bound by transcription factors. They may help explain why transcriptional regulation is implicated in many more evolutionary adaptations and innovations than RNA-mediated gene regulation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Evolutionary Biology and Environmental Studies
Dewey Decimal Classification:570 Life sciences; biology
590 Animals (Zoology)
Uncontrolled Keywords:Multidisciplinary
Language:English
Date:10 April 2018
Deposited On:05 Mar 2019 14:34
Last Modified:25 Sep 2019 00:22
Publisher:National Academy of Sciences of the United States of America
ISSN:1091-6490
OA Status:Closed
Publisher DOI:https://doi.org/10.1073/pnas.1719138115
Project Information:
  • : FunderSNSF
  • : Grant IDPP00P3_170604
  • : Project TitleRegulatory logic and the evolution of promoter complexity
  • : FunderSNSF
  • : Grant IDPZ00P3_154773
  • : Project TitleThe evolution and robustness of transcription factor binding sites
  • : FunderSNSF
  • : Grant ID31003A_172887
  • : Project TitleRobustness and weakened selection in the adaptive evolution of fluorescent proteins
  • : FunderH2020
  • : Grant ID739874
  • : Project TitleNoiseRobustEvo - Noise and robustness in the evolution of novel protein phenotypes

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