Gabriela Gomes (University of Strathclyde) – Remodelling Selection to overcome Selective Depletion Biases

Every population consists of individuals that vary in many traits, and each trait may or may not be associated with fitness. Variation in fitness traits lends population studies prone to selective depletion biases. When an ageing cohort exhibits declining mortality, it could be individuals becoming healthier or selective depletion of the frail. In an epidemic, when growth in cumulative infections decelerates, it could be individuals cautiously changing behaviour or selective depletion of the most susceptible. In microbial populations, when an isogenic population is stressed by antimicrobial treatment and some cells survive, this could be due to individual cells switching between normal and persister phenotypes or antibiotic selectively killing cells that divide faster. In each case, the first explanation invokes individuals changing (1), while the second posits selection on pre-existing variation changing (2). While explanations of type (1) are intuitive and widely adopted, those of type (2) are more neutral and rarely considered due to cognitive biases and challenges in estimating all variation that matters. While both are plausibly operating in most real systems, neglect of (2) leads to over-attribution of results to (1), wrong predictions, bad policy decisions and poor reproducibility, negatively impacting science, economics and ethics.

To overcome this selective depletion bias, we propose a pragmatic approach to study design and analysis whereby we infer distributions of characteristics that respond to selection and reframe theories accordingly. The approach is based on remodelling selection (mathematically by introducing key parametric distributions into population dynamic models, and empirically by measuring quantities of interest along selection gradients) and statistical inference (by fitting mathematical models to data). The procedure is being tested in systems where trait distributions can be inferred from population trends as well as reconstructed directly from individual measurements. Results of this ongoing research will be presented, and the wider applicability discussed.