Fink, J. W. | Search bioRxiv

bioRxiv2024

Quantifying microbial fitness in high-throughput experiments

Few concepts are as central to evolution as is fitness, and yet the quantification of fitness is often ambiguous. In particular, high-throughput experiments to measure mutant fitness in microbes are increasingly common but vary widely in their definitions of fitness, which makes their results difficult to compare. What are the consequences of these different fitness statistics, and is there a best way to quantify fitness in a given context? Here we systematize the set of possible fitness statistics according to the following three choices: 1) the encoding of relative abundance (e.g., transforming by a log or logit function), 2) the time scale over which to measure the change in relative abundance, and 3) the choice of a reference subpopulation for calculating relative fitness in bulk competition experiments, such as those using DNA-barcoded mutants. We show that these different choices can lead to significantly different interpretations of mutant fitness, affecting the magnitude of fitness effects, the apparent presence of epistasis, and even the fitness ranking across mutants. This can confound predictions for evolutionary dynamics and gene functions. Altogether our results demonstrate the importance of consistent fitness definitions for reproducible results across experiments.

evolutionary biology↗

bioRxiv2022

Microbial population dynamics decouple nutrient affinity from environmental concentration

How the growth rate of a microbial population responds to the environmental availability of chemical nutrients and other resources is a fundamental question in microbiology. Models of this response, such as the widely-used Monod model, are generally characterized by a maximum growth rate and a half-saturation concentration of the resource. What values should we expect for these half-saturation concentrations, and how should they depend on the environmental concentration of the resource? We survey growth response data across a wide range of organisms and resources. We find that the half-saturation concentrations vary across orders of magnitude, even for the same organism and resource. To explain this variation, we develop an evolutionary model to show that demographic fluctuations (genetic drift) can constrain the adaptation of half-saturation concentrations. We find that this effect fundamentally differs depending on the type of population dynamics: populations undergoing periodic bottlenecks of fixed size will adapt their half-saturation concentration in proportion to the environmental resource concentration, but populations undergoing periodic dilutions of fixed size will evolve half-saturation concentrations that are largely decoupled from the environmental concentration. Our model not only provides testable predictions for laboratory evolution experiments, but it also reveals how an evolved half-saturation concentration may not reflect the organisms environment. In particular, this explains how organisms in resource-rich environments can still evolve fast growth at low resource concentrations. Altogether our results demonstrate the critical role of population dynamics in shaping fundamental ecological traits.

microbiology↗