Abstract
Cells adapt to familiar changes in their environment by activating predefined regulatory programs that establish adaptive gene expression states. These hard-wired pathways, however, may be inadequate for adaptation to environments never encountered before. Here, we reveal evidence for an alternative mode of gene regulation that enables adaptation to adverse conditions without relying on external sensory information or genetically predetermined cis-regulation. Instead, individual genes achieve optimal expression levels through a stochastic search for improved fitness. By focusing on improving the overall health of the cell, the proposed stochastic tuning mechanism discovers global gene expression states that are fundamentally new and yet optimized for novel environments. We provide experimental evidence for stochastic tuning in the adaptation of Saccharomyces cerevisiae to laboratory-engineered environments that are foreign to its native gene-regulatory network. Stochastic tuning operates locally at individual gene promoters, and its efficacy is modulated by perturbations to chromatin modification machinery.
Highlights
The capacity to adapt to changes in the external environment is a defining feature of living systems
Cells can rapidly adapt to familiar changes that are commonly encountered in their native habitat by sensing the parameters of the environment and engaging dedicated regulatory networks that have evolved to establish adaptive gene expression states (Jacob and Monod, 1961; Thieffry et al, 1998)
We asked whether individual genes could, in principle, carry out a search process equivalent to gradient descent (Cauchy, 1847), where the health consequence of stochastic alterations in gene expression could gradually tune the expression of individual genes towards a level that is optimal for internal health
Summary
The capacity to adapt to changes in the external environment is a defining feature of living systems. At least one gene expression state that maximizes the health/fitness of the cell always exists, despite the inability of the native regulatory network to establish such a state. This is true because under any conceivable environment, the activities of some genes are beneficial, whereas those of others are futile or even actively detrimental (Jacob and Monod, 1961; Tagkopoulos et al, 2008; Hottes et al, 2013). If the initial fitness defect is not lethal, a population of cells may slowly adapt to an unfamiliar environment through the accumulation of genetic mutations that rewire regulatory networks, thereby achieving more optimal gene expression states (Tagkopoulos et al, 2008; Applebee et al, 2008; Philippe et al, 2007; Goodarzi et al, 2010; Tenaillon et al, 2012; Rodrıguez-Verdugo et al, 2016; Blount et al, 2012; Van Hofwegen et al, 2016; Damkiær et al, 2013)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
