Regulatory network structure determines patterns of intermolecular epistasis

Lagator, Mato, Sarikas, Srdjan, Acar, Hande ORCID: 0000-0003-1986-9753, Bollback, Jonathan P ORCID: 0000-0002-4624-4612 and Guet, Calin C
(2017) Regulatory network structure determines patterns of intermolecular epistasis. eLife, 6.

[img] Text
elife-28921-v1 (1).pdf - Accepted Version

Download (24MB)


Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 14 Nov 2017 10:32
Last Modified: 16 Apr 2021 11:21
DOI: 10.7554/eLife.28921
Related URLs: