Abstract
Loss of gene function is common throughout evolution, even though it often leads to reduced fitness. In this study, we systematically evaluated how an organism adapts after deleting genes that are important for growth under oxidative stress. By evolving, sequencing, and phenotyping over 200 yeast lineages, we found that gene loss can enhance an organism’s capacity to evolve and adapt. Although gene loss often led to an immediate decrease in fitness, many mutants rapidly acquired suppressor mutations that restored fitness. Depending on the strain’s genotype, some ultimately even attained higher fitness levels than similarly adapted wild-type cells. Further, cells with deletions in different modules of the genetic network followed distinct and predictable mutational trajectories. Finally, losing highly connected genes increased evolvability by facilitating the emergence of a more diverse array of phenotypes after adaptation. Together, our findings show that loss of specific parts of a genetic network can facilitate adaptation by opening alternative evolutionary paths.
Highlights
Loss of gene function is common in nature
We focused on genes important for resistance to oxidative stress, a trait involved in multiple disease phenotypes including cancer, neurodegenerative disorders and age-related diseases (Barnham et al 2004; Reuter et al 2010)
The results reveal the importance of genotype and genetic architecture during adaption to gene loss
Summary
Loss of gene function is common in nature. An average human, for example, carries about 100 loss-of-function variants in their genome (MacArthur et al 2012). When a budding yeast cell loses a gene, the effect on fitness in any given condition can vary from beneficial to lethal (Giaever et al 2002) This pattern of essentiality and dispensability depends on the genetic background, with some genes being essential in one genotype and dispensable in another (Dowell et al 2010; Liu et al 2015). Reports that link the function of the lost genes with the mutations acquired during adaptation are based either on small, case-specific experiments (Rancati et al 2008; Laan et al 2015) or on larger-scale screens where convergent evolution between strains with defects in similar processes was rare, which precludes drawing strong general conclusions on the adaptive routes and overall evolutionary consequences of gene loss (Szamecz et al 2014; Rojas Echenique et al 2019). Including information about an organism’s genetic network architecture is crucial for understanding how and why a cell compensates in a specific way for the loss of a particular gene
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
