Biology subjects

Kingma, E.

Publications and source records attributed to Kingma, E..

3 recordsLinked to original sources

bioRxiv2024

Mutations compensating for cell polarity defects change the gene-fitness relationship on a genome-wide scale

Functional defects resulting from deleterious mutations can often be restored during evolution by compensatory mutations elsewhere in the genome. Importantly, this process can generate the genetic diversity seen in networks regulating the same biological function in different species. How the options for compensatory evolution depend on the molecular interactions underlying these functions is currently unclear. In this study, we investigate how gene deletions compensating for a defect in the polarity pathway of Saccharomyces cerevisiae impact the fitness landscape. Using a transposon mutagenesis screen, we demonstrate that gene fitness has changed on a genome-wide scale in the compensated strain. An analysis of the functional associations between the affected genes reveals that compensation impacts cellular processes that have no clear connection to cell polarity. Moreover, genes belonging to the same process tend to show the same direction of gene fitness change, indicating that compensation rewires the fitness contribution of cellular processes rather than of individual genes. In conclusion, our results strongly suggest that functional overlap between modules and the interconnectedness of the molecular interaction network play major roles in mediating compensatory evolution.

evolutionary biology↗

bioRxiv2023

Saturated Transposon Analysis in Yeast as a One-step Method to Quantify the Fitness Effects of Gene Disruptions on a Genome-Wide Scale

Transposon insertion site sequencing (TIS) is an extremely powerful tool that has greatly advanced our knowledge of functional genomics. However, studies using TIS often focus on gene essentiality and neglect possibly interesting but subtle differences in the importance of genes for fitness. As shown by other studies, expanding of the analysis of TIS data to allow a quantitative estimate of fitness has important application in genetics and evolutionary biology. Here, we present a method to estimate the fitness of gene disruption mutants on a quantitative level using data obtained from a TIS screen developed for the yeast Saccharomyces cerevisiae called SATAY. We show that using the average read count per transposon insertion site provides a metric for fitness that is robust across biological and technical replicate experiments. Importantly, the ability to resolve differences between gene disruption mutants with low fitness depends crucially on the inclusion of insertion sites that are not observed in the sequencing data to estimate the mean. While our method provides reproducible results between replicate SATAY datasets, the obtained fitness distribution differs substantially from those obtained using other techniques. It remains unclear whether these inconsistencies are due to biological or technical differences between the methods. Finally, we give suggestions for modifications of the SATAY procedure that could improve the resolution of the fitness estimates. Our analysis indicates that increasing the sequencing depth does very little to reduce the uncertainty in the estimates, while replacing the PCR amplification with methods that avoid or reduce the number of amplification cycles will likely be most effective in reducing noise.

evolutionary biology↗

bioRxiv2020

Pleiotropy allows recovery of phenotypic plasticity in constant environments

Phenotypic plasticity confers a fitness advantage to an organism by tailoring phenotype to environmental circumstances. The extent to which phenotypic plasticity emerges as an adaptive response is still unknown, however it is predicted that the emergence and maintenance of phenotypic plasticity occurs only during evolution in fluctuating environments. Interestingly, experimental studies have shown that phenotypic plasticity can be preserved for several generations during evolution in a constant environment. Here, we evolve a mutant strain of Saccharomyces cerevisiae that has reduced plasticity in a constant and fluctuating environment. Subsequently we compared the adaptive response of the evolved cell, both at the phenotype and genotype level. As predicted by current theory, we find that evolution in a fluctuating environment results in a recovery of phenotypic plasticity. Surprisingly, evolution in a constant environment can lead to a similar recovery of plasticity due to a pleiotropic coupling of different traits. Thus, plasticity can emerge in both fluctuating and constant environments and its prevalence may mainly be determined by network structure. In addition, pleiotropic interactions may be an important structural component of biological networks that can facilitate the recovery of phenotypic plasticity without the requirement to continuously encounter environmental fluctuations.

evolutionary biology↗