Estrutura de rede reguladora determina os padrões de epistasia intermolecular

segunda-feira, fevereiro 12, 2018

Regulatory network structure determines patterns of intermolecular epistasis

Mato Lagator Srdjan Sarikas Hande Acar Jonathan P Bollback Călin C Guet 

Institute of Science and Technology Austria, Austria University of Liverpool, United Kingdom


Source/Fonte: Utah Edu.


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.