The fitness cost and benefit of phase‐separated protein deposits

Molecular Systems Biology

Salvador Ventura¹  Charles NJ Ravarani²  Natalia Sanchez de Groot²  M Madan Babu²  Marc Torrent Burgas²  Ala Trusina³ 

[1] Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular Universitat Autònoma de Barcelona Barcelona Spain;Medical Research Council Laboratory of Molecular Biology Cambridge UK;Niels Bohr Institute University of Copenhagen Copenhagen Denmark;

关键词: cell fitness;    natural selection;    phase separation;    phenotypic diversity;    protein deposit;   

DOI  :  10.15252/msb.20178075

来源: DOAJ

【 摘 要 】

Abstract Phase separation of soluble proteins into insoluble deposits is associated with numerous diseases. However, protein deposits can also function as membrane‐less compartments for many cellular processes. What are the fitness costs and benefits of forming such deposits in different conditions? Using a model protein that phase‐separates into deposits, we distinguish and quantify the fitness contribution due to the loss or gain of protein function and deposit formation in yeast. The environmental condition and the cellular demand for the protein function emerge as key determinants of fitness. Protein deposit formation can influence cell‐to‐cell variation in free protein abundance between individuals of a cell population (i.e., gene expression noise). This results in variable manifestation of protein function and a continuous range of phenotypes in a cell population, favoring survival of some individuals in certain environments. Thus, protein deposit formation by phase separation might be a mechanism to sense protein concentration in cells and to generate phenotypic variability. The selectable phenotypic variability, previously described for prions, could be a general property of proteins that can form phase‐separated assemblies and may influence cell fitness.

【 授权许可】

Unknown