Biology subjects

Plotkin, J. B.

Publications and source records attributed to Plotkin, J. B..

5 recordsLinked to original sources

bioRxiv2018

Evolution of empathetic moral evaluation

Social norms can promote cooperation in human societies by assigning reputations to individuals based on their past actions. A good reputation indicates that an individual is worthy of help and is likely to reciprocate. A large body of research has established the norms of moral assessment that promote cooperation and maximize social welfare, assuming reputations are objective. But if there is no centralized institution to provide objective moral evaluation, then opinions about an individuals reputation may differ across a population. Here we use evolutionary game theory to study the effects of empathy - the capacity to make moral evaluations from the perspective of another person. We find that empathetic moral evaluation tends to foster cooperation by reducing the rate of unjustified defection. The norms of moral evaluation previously considered most socially beneficial depend on high levels of empathy, whereas different norms are required to maximize social welfare in populations unwilling or incapable of empathy. We demonstrate that empathy itself can evolve through social contagion and attain evolutionary stability under most social norms. We conclude that a capacity for empathetic moral evaluation represents a key component to sustaining cooperation in human societies: cooperation requires getting into the mindset of others whose views differ from our own.

evolutionary biology↗

bioRxiv2018

Codon usage influences fitness through RNA toxicity

Many organisms are subject to selective pressure that gives rise to unequal usage of synonymous codons, known as codon bias. To experimentally dissect the mechanisms of selection on synonymous sites, we expressed several hundred synonymous variants of the GFP gene in Escherichia coli, and used quantitative growth and viability assays to estimate bacterial fitness. Unexpectedly, we found many synonymous variants whose expression was toxic to E. coli. Unlike previously studied effects of synonymous mutations, the effect that we discovered is independent of translation, but it depends on the production of toxic mRNA molecules. We identified RNA sequence determinants of toxicity, and evolved suppressor strains that can tolerate the expression of toxic GFP variants. Genome sequencing of these suppressor strains revealed a cluster of promoter mutations that prevented toxicity by reducing mRNA levels. We conclude that translation-independent RNA toxicity is a previously unrecognized obstacle in bacterial gene expression.\n\nSignificance statementSynonymous mutations in genes do not change protein sequence, but they may affect gene expression and cellular function. Here we describe an unexpected toxic effect of synonymous mutations in Escherichia coli, with potentially large implications for bacterial physiology and evolution. Unlike previously studied effects of synonymous mutations, the effect that we discovered is independent of translation, but it depends on the production of toxic mRNA molecules. We hypothesize that the mechanism we identified influences the evolution of endogenous genes in bacteria, by imposing selective constraints on synonymous mutations that arise in the genome. Of interest for biotechnology and synthetic biology, we identify bacterial strains and growth conditions that alleviate RNA toxicity, thus allowing efficient overexpression of heterologous proteins.

synthetic biology↗

bioRxiv2018

Selection for protein stability enriches for epistatic interactions

A now classical argument for the marginal thermodynamic stability of proteins explains the distribution of observed protein stabilities as a consequence of an entropic pull in protein sequence space. In particular, most sequences that are sufficiently stable to fold will have stabilities near the folding threshold. Here we extend this argument to consider its predictions for epistatic interactions for the effects of mutations on the free energy of folding. Although there is abundant evidence to indicate that the effects of mutations on the free energy of folding are nearly additive and conserved over evolutionary time, we show that these observations are compatible with the hypothesis that a non-additive contribution to the folding free energy is essential for observed proteins to maintain their native structure. In particular through both simulations and analytical results, we show that even very small departures from additivity are sufficient to drive this effect.

evolutionary biology↗

bioRxiv2017

riboviz: analysis and visualization of ribosome profiling datasets

Using high-throughput sequencing to monitor translation in vivo, ribosome profiling can provide critical insights into the dynamics and regulation of protein synthesis in a cell. Since its introduction in 2009, this technique has played a key role in driving biological discovery, and yet it requires a rigorous computational toolkit for widespread adoption. We developed a processing pipeline and browser-based visualization, riboviz, that allows convenient exploration and analysis of riboseq datasets. In implementation, riboviz consists of a comprehensive and flexible backend analysis pipeline that allows the user to analyze their private unpublished dataset, along with a web application for comparison with previously published public datasets.\n\nAvailability and implementationJavaScript and R source code and extra documentation are freely available from https://github.com/shahpr/RiboViz, while the web-application is live at www.riboviz.org.

bioinformatics↗

bioRxiv2016

Phenotypic plasticity can facilitate evolutionary rescue

Environmental variation is commonplace, but unpredictable. Populations that encounter a deleterious environment can sometimes avoid extinction by rapid evolutionary adaptation. Phenotypic variability, whereby a single genotype can express multiple different phenotypes, might play an important role in rescuing such populations from extinction. This type of evolutionary bet-hedging need not confer a direct benefit to a single individual, but it may increase the chance of long-term survival of a lineage. Here we develop a population-genetic model to explore how partly heritable phenotypic variability influences the probability of evolutionary rescue and the mean duration of population persistence in changing environments. We find that the probability of population persistence depends non-monotonically on the degree of phenotypic heritability between generations: some heritability can help avert extinction, but too much heritability removes any benefit of phenotypic variability. We discuss the implications of these results in the context of therapies designed to eradicate populations of pathogens or aberrant cellular lineages.

evolutionary biology↗