Patterns of genetic variation in populations of infectious agents

摘要

Background The analysis of genetic variation in populations of infectious agents may help us understand their epidemiology and evolution. Here we study a model for assessing the levels and patterns of genetic diversity in populations of infectious agents. The population is structured into many small subpopulations, which correspond to their hosts, that are connected according to a specific type of contact network. We considered different types of networks, including fully connected networks and scale free networks, which have been considered as a model that captures some properties of real contact networks. Infectious agents transmit between hosts, through migration, where they grow and mutate until elimination by the host immune system. Results We show how our model is closely related to the classical SIS model in epidemiology and find that: depending on the relation between the rate at which infectious agents are eliminated by the immune system and the within host effective population size, genetic diversity increases with R₀ or peaks at intermediate R₀ levels; patterns of genetic diversity in this model are in general similar to those expected under the standard neutral model, but in a scale free network and for low values of R₀ a distortion in the neutral mutation frequency spectrum can be observed; highly connected hosts (hubs in the network) show patterns of diversity different from poorly connected individuals, namely higher levels of genetic variation, lower levels of genetic differentiation and larger values of Tajima's D. Conclusion We have found that levels of genetic variability in the population of infectious agents can be predicted by simple analytical approximations, and exhibit two distinct scenarios which are met according to the relation between the rate of drift and the rate at which infectious agents are eliminated. In one scenario the diversity is an increasing function of the level of transmission and in a second scenario it is peaked around intermediate levels of transmission. This is independent of the type of host contact structure. Furthermore for low values of R₀, very heterogeneous host contact structures lead to lower levels of diversity.