Multiple scales of selection influence the evolutionary emergence of novel pathogens

Abstract

One contribution of 18 to a Discussion Meeting Issue 'Next-generation molecular and evolutionary epidemiology of infectious disease'. When pathogens encounter a novel environment, such as a new host species or treatment with an antimicrobial drug, their fitness may be reduced so that adaptation is necessary to avoid extinction. Evolutionary emergence is the process by which new pathogen strains arise in response to such selective pressures. Theoretical studies over the last decade have clarified some determinants of emergence risk, but have neglected the influence of fitness on evolutionary rates and have not accounted for the multiple scales at which pathogens must compete successfully. We present a cross-scale theory for evolutionary emergence, which embeds a mechanistic model of withinhost selection into a stochastic model for emergence at the population scale. We explore how fitness landscapes at within-host and between-host scales can interact to influence the probability that a pathogen lineage will emerge successfully. Results show that positive correlations between fitnesses across scales can greatly facilitate emergence, while cross-scale conflicts in selection can lead to evolutionary dead ends. The local genotype space of the initial strain of a pathogen can have disproportionate influence on emergence probability. Our cross-scale model represents a step towards integrating laboratory experiments with field surveillance data to create a rational framework to assess emergence risk.

The Effect of Immunodeficiency on the Evolution of Virulence: An Experimental Test with the Rodent MalariaPlasmodium chabaudi

“…We have also bypassed mosquito transmission, a possible source of selection against virulence in this system (Ebert 1998), though we note that virulence differences generated by protocols very similar to ours are not eliminated by mosquito transmission (Mackinnon and Read 2004a;Mackinnon et al 2005). If the directions of within-and between-host selection on virulence are in opposition, the question is how evolution would play out in nature (Park et al 2013). Our data are consistent with positive withinhost selection for virulence generated by immunodeficiency.…”

Expected Effect of Deleterious Mutations on Within-Host Adaptation of Pathogens

“…Although some models have recognized the importance of deleterious intermediates and the crossing of fitness valleys to the overall adaptive evolution of pathogens (27,29,42,43) and the possibility that multiple simultaneous mutations can overcome such fitness valleys (44), various other models assume a strong selection-weak mutation paradigm (32)(33)(34)45), ignoring any adaptive trajectories that require the crossing of a fitness valley. Such assumptions might be appropriate for small population sizes or pathogens with low mutation rates (5,30).…”

“…Therefore, calculations on the effects of fitness valleys are of critical importance in assessments of the pandemic risk of emerging pathogens (8,33,35,44,67,68) and, in addition, to inform the cost-benefit analyses of gain-of-function experiments and dualuse research of concern.…”

“…A methodological framework that is frequently used to study pathogen evolution and that makes such assumptions is the strong selection-weak mutation (SSWM) approximation (30,31). Models using the SSWM assumption describe the evolutionary trajectory of a population where selective sweeps cause the sequential fixation of advantageous mutations, while deleterious or neutral mutations are disregarded (32)(33)(34).…”

Identifying Selection in the Within-Host Evolution of Influenza Using Viral Sequence Data

“…Considering data of intracellular RNA levels, the fine detail of viral replication within a cell has been described [15]. Evolutionary models of competition between viral strains have clarified the relationship between selection for growth and transmission effects, and the dynamics of immune escape [16]–[18].…”