Biology subjects

Libby, E.

Publications and source records attributed to Libby, E..

4 recordsLinked to original sources

bioRxiv2018

Disentangling the effects of genetic architecture, mutational bias and selection on evolutionary forecasting

Predicting evolutionary change poses numerous challenges. Here we take advantage of the model bacterium Pseudomonas fluorescens in which the genotype-to-phenotype map determining evolution of the adaptive \"wrinkly spreader\" (WS) type is known. We present mathematical descriptions of three necessary regulatory pathways and use these to predict both the rate at which each mutational route is used and the expected mutational targets. To test predictions, mutation rates and targets were determined for each pathway. Unanticipated mutational hotspots caused experimental observations to depart from predictions but additional data led to refined models. A mismatch was observed between the spectra of WS-causing mutations obtained with and without selection due to low fitness of previously undetected WS-causing mutations. Our findings contribute toward the development of mechanistic models for forecasting evolution, highlight current limitations, and draw attention to challenges in predicting locus-specific mutational biases and fitness effects.\n\nImpact statementA combination of genetics, experimental evolution and mathematical modelling defines information necessary to predict the outcome of short-term adaptive evolution.

evolutionary biology↗

bioRxiv2018

Multisite phosphorylation regulates phenotypic variability in antibiotic tolerance

Isogenic populations of cells exhibit phenotypic variability that has specific physiological consequences. For example, individual bacteria within a population can differ in their sensitivity to an antibiotic, but whether this variability can be regulated or is generally an unavoidable consequence of stochastic fluctuations is unclear. We observed that a bacterial stress response gene, the (p)ppGpp synthetase sasA, exhibits high levels of extrinsic noise in expression, suggestive of a regulatory process. We traced this variability to the convergence of two signaling systems that together control the multisite phosphorylation of a transcription factor, an event largely unexplored in bacteria, This regulatory intersection between a Ser/Thr kinase and a prototypical two component system is crucial for controlling the appearance of outliers, rare cells with unusually high levels of sasA expression. Additionally, by examining the full distributions of gene expression we calculated the contribution of the additional Ser/Thr kinase-dependent phosphorylation in setting the relative abundance of cells with a given a level of SasA. We then created a predictive model for the probability of a given cell surviving antibiotic treatment as a function of sasA expression. Therefore, our data show that multisite phosphorylation can be used to strongly regulate variations in phenotypes across a bacterial population.

microbiology↗

bioRxiv2018

Ecological advantages and evolutionary limitations of aggregative multicellular development

All multicellular organisms develop through one of two basic routes: they either aggregate from free-living cells, creating potentially-chimeric multicellular collectives, or they develop clonally via mother-daughter cellular adhesion. While evolutionary theory makes clear predictions about trade-offs between these developmental modes, these have never been experimentally tested in otherwise genetically-identical organisms. We engineered unicellular bakers yeast (Saccharomyces cerevisiae) to develop either clonally ( snowflake, {Delta}ace2), or aggregatively ( floc, GAL1p::FLO1), and examined their fitness in a fluctuating environment characterized by periods of growth and selection for rapid sedimentation. When cultured independently, aggregation was far superior to clonal development, providing a 35% advantage during growth, and a 2.5-fold advantage during settling selection. Yet when competed directly, clonally-developing snowflake yeast rapidly displaced aggregative floc. This was due to unexpected social exploitation: snowflake yeast, which do not produce adhesive FLO1, nonetheless become incorporated into flocs at a higher frequency than floc cells themselves. Populations of chimeric clusters settle much faster than floc alone, providing snowflake yeast with a fitness advantage during competition. Mathematical modeling suggests that such developmental cheating may be difficult to circumvent; hypothetical choosy floc that avoid exploitation by maintaining clonality pay an ecological cost when rare, often leading to their extinction. Our results highlight the conflict at the heart of aggregative development: non-specific cellular binding provides a strong ecological advantage - the ability to quickly form groups - but this very feature leads to its exploitation.

evolutionary biology↗

bioRxiv2016

Paradoxes in Leaky Microbial Trade

Microbes produce metabolic resources that are important for cell growth yet leak across membranes into the extracellular environment. Other microbes in the same environment can use these resources and adjust their own metabolic production accordingly--causing other resources to leak into the environment. The combined effect of these processes is an economy in which organismal growth and metabolic production are coupled to others in the community. We propose a model for the co-evolving dynamics of metabolite concentrations, production regulation, and population frequencies for the case of two cell types, each requiring and capable of producing two metabolites. In this model, beneficial trade relations emerge without any coordination, via individual-level production decisions that maximize each cells growth rate given its perceived environment. As we vary production parameters of the model, we encounter three paradoxical behaviors, where a change that should intuitively benefit some cell type, actually harms it. (1) If a cell type is more efficient than its counterpart at producing a metabolite and becomes even more efficient, its frequency in the population can decrease. (2) If a cell type is less efficient than its counterpart at producing a metabolite but becomes less inefficient, the growth rate of the population can decrease. (3) Finally, if a cell type controls its counterparts production decisions so as to maximize its own growth rate, the ultimate growth rate it achieves can be lower than if the two cell types each maximized their own growth. These three paradoxes highlight the complex and counter-intuitive dynamics that emerge in simple microbial economies.

microbiology↗