Trade-offs in virulence evolution: a Hierarchy-of-Hypotheses approach

Understanding the evolution of virulence, that is, the harm pathogens cause their hosts, has major and wide-spread repercussions. A central concept of virulence evolution is the so-called 'trade-off hypothesis', a seemingly straightforward relationship between virulence and transmission. However, substantial ambiguity in terminology related to this hypothesis threatens progress in the field. To address this, we apply a Hierarchy-of-Hypotheses approach to provide structured, visual representations of ideas linked to this hypothesis. We illustrate that the trade-off hypothesis is a complex set of many different hypotheses and trade-offs, and we clarify ambiguities and biases in commonly used terminology in the literature. Thereby, we hope to facilitate a more precise understanding of what the trade-off hypothesis means, enabling more targeted and precise hypothesis testing.