RESUMEN
High-throughput sequencing has opened the route for a deep assessment of within-host genetic diversity that can be used, e.g., to characterize microbial communities and to infer transmission links in infectious disease outbreaks. The performance of such characterizations and inferences cannot be analytically assessed in general and are often grounded on computer-intensive evaluations. Then, being able to simulate within-host genetic diversity across time under various demo-genetic assumptions is paramount to assess the performance of the approaches of interest. In this context, we built an original model that can be simulated to investigate the temporal evolution of genotypes and their frequencies under various demo-genetic assumptions. The model describes the growth and the mutation of genotypes at the nucleotide resolution conditional on an overall within-host viral kinetics, and can be tuned to generate fast non-equilibrium demo-genetic dynamics. We ran simulations of this model and computed classic diversity indices to characterize the temporal variation of within-host genetic diversity (from high-throughput amplicon sequences) of virus populations under three demographic kinetic models of viral infection. Our results highlight how demographic (viral load) and genetic (mutation, selection, or drift) factors drive variations in within-host diversity during the course of an infection. In particular, we observed a non-monotonic relationship between pathogen population size and genetic diversity, and a reduction of the impact of mutation on diversity when a non-specific host immune response is activated. The large variation in the diversity patterns generated in our simulations suggests that the underlying model provides a flexible basis to produce very diverse demo-genetic scenarios and test, for instance, methods for the inference of transmission links during outbreaks.
RESUMEN
Pathogens and pollutants, such as pesticides, are potential stressors to all living organisms, including honey bees. Herbicides and fungicides are among the most prevalent pesticides in beehive matrices, and their interaction with Nosema ceranae is not well understood. In this study, the interactions between N. ceranae, the herbicide glyphosate and the fungicide difenoconazole were studied under combined sequential and overlapping exposure to the pesticides at a concentration of 0.1 µg/L in food. In the sequential exposure experiment, newly emerged bees were exposed to the herbicide from day 3 to day 13 after emerging and to the fungicide from day 13 to day 23. In the overlapping exposure experiment, bees were exposed to the herbicide from day 3 to day 13 and to the fungicide from day 7 to day 17. Infection by Nosema in early adult life stages (a few hours post emergence) greatly affected the survival of honey bees and elicited much higher mortality than was induced by pesticides either alone or in combination. Overlapping exposure to both pesticides induced higher mortality than was caused by sequential or individual exposure. Overlapping, but not sequential, exposure to pesticides synergistically increased the adverse effect of N. ceranae on honey bee longevity. The combination of Nosema and pesticides had a strong impact on physiological markers of the nervous system, detoxification, antioxidant defenses and social immunity of honey bees.
