@article {125200, title = {The layered costs and benefits of translational redundancy.}, journal = {Elife}, volume = {12}, year = {2023}, month = {2023 Mar 02}, abstract = {

The rate and accuracy of translation hinges upon multiple components - including transfer RNA (tRNA) pools, tRNA modifying enzymes, and rRNA molecules - many of which are redundant in terms of gene copy number or function. It has been hypothesized that the redundancy evolves under selection, driven by its impacts on growth rate. However, we lack empirical measurements of the fitness costs and benefits of redundancy, and we have poor a understanding of how this redundancy is organized across components. We manipulated redundancy in multiple translation components of by deleting 28 tRNA genes, 3 tRNA modifying systems, and 4 rRNA operons in various combinations. We find that redundancy in tRNA pools is beneficial when nutrients are plentiful and costly under nutrient limitation. This nutrient-dependent cost of redundant tRNA genes stems from upper limits to translation capacity and growth rate, and therefore varies as a function of the maximum growth rate attainable in a given nutrient niche. The loss of redundancy in rRNA genes and tRNA modifying enzymes had similar nutrient-dependent fitness consequences. Importantly, these effects are also contingent upon interactions across translation components, indicating a layered hierarchy from copy number of tRNA and rRNA genes to their expression and downstream processing. Overall, our results indicate both positive and negative selection on redundancy in translation components, depending on a species{\textquoteright} evolutionary history with feasts and famines.

}, keywords = {Biological Evolution, Cost-Benefit Analysis, Escherichia coli, Exercise, Gene Dosage}, issn = {2050-084X}, doi = {10.7554/eLife.81005}, author = {Raval, Parth K and Ngan, Wing Yui and Gallie, Jenna and Agashe, Deepa} } @article {88404, title = {The Impact of Mistranslation on Phenotypic Variability and Fitness.}, journal = {Evolution}, year = {2021}, month = {01/2021}, abstract = {

Phenotypic variation is widespread in natural populations, and can significantly alter population ecology and evolution. Phenotypic variation often reflects underlying genetic variation, but also manifests via non-heritable mechanisms. For instance, translation errors result in about 10\% of cellular proteins carrying altered sequences. Thus, proteome diversification arising from translation errors can potentially generate phenotypic variability, in turn increasing variability in the fate of cells or of populations. However, the link between protein diversity and phenotypic variability remains unverified. We manipulated mistranslation levels in Escherichia coli, and measured phenotypic variability between single cells (individual level variation), as well as replicate populations (population level variation). Monitoring growth and survival, we find that mistranslation indeed increases variation across E. coli cells, but does not consistently increase variability in growth parameters across replicate populations. Interestingly, although any deviation from the wild type (WT) level of mistranslation reduces fitness in an optimal environment, the increased variation is associated with a survival benefit under stress. Hence, we suggest that mistranslation-induced phenotypic variation can impact growth and survival and has the potential to alter evolutionary trajectories. This article is protected by copyright. All rights reserved.

}, doi = {10.1111/evo.14179}, author = {Samhita, Laasya and Raval, Parth K and Stephenson, G and Thutupalli, Shashi and Agashe, Deepa} } @article {74445, title = {Global mistranslation increases cell survival under stress in Escherichia coli.}, journal = {PLoS Genet}, volume = {16}, year = {2020}, month = {2020 Mar 09}, pages = {e1008654}, abstract = {

Mistranslation is typically deleterious for cells, although specific mistranslated proteins can confer a short-term benefit in a particular environment. However, given its large overall cost, the prevalence of high global mistranslation rates remains puzzling. Altering basal mistranslation levels of Escherichia coli in several ways, we show that generalized mistranslation enhances early survival under DNA damage, by rapidly activating the SOS response. Mistranslating cells maintain larger populations after exposure to DNA damage, and thus have a higher probability of sampling critical beneficial mutations. Both basal and artificially increased mistranslation increase the number of cells that are phenotypically tolerant and genetically resistant under DNA damage; they also enhance survival at high temperature. In contrast, decreasing the normal basal mistranslation rate reduces cell survival. This wide-ranging stress resistance relies on Lon protease, which is revealed as a key effector that induces the SOS response in addition to alleviating proteotoxic stress. The new links between error-prone protein synthesis, DNA damage, and generalised stress resistance indicate surprising coordination between intracellular stress responses and suggest a novel hypothesis to explain high global mistranslation rates.

}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1008654}, author = {Samhita, Laasya and Raval, Parth K and Agashe, Deepa} }