An official website of the United States government
Abstract The infection of cells by multiple copies of a given virus can impact viral evolution in a variety of ways, yet some of the most basic evolutionary dynamics remain underexplored. Using computational models, we investigate how infection multiplicity affects the fixation probability of mutants, the rate of mutant generation, and the timing of mutant invasion. An important insight from these models is that for neutral and disadvantageous phenotypes, rare mutants initially enjoy a fitness advantage in the presence of multiple infection of cells. This arises because multiple infection allows the rare mutant to enter more target cells and to spread faster, while it does not accelerate the spread of the resident wild-type virus. The rare mutant population can increase by entry into both uninfected and wild-type-infected cells, while the established wild-type population can initially only grow through entry into uninfected cells. Following this initial advantageous phase, the dynamics are governed by drift or negative selection, respectively, and a higher multiplicity reduces the chances that mutants fix in the population. Hence, while increased infection multiplicity promotes the presence of neutral and disadvantageous mutants in the short-term, it makes it less likely in the longer term. We show how these theoretical insights can be useful for the interpretation of experimental data on virus evolution at low and high multiplicities. The dynamics explored here provide a basis for the investigation of more complex viral evolutionary processes, including recombination, reassortment, as well as complementary/inhibitory interactions.
more »
« less
Mutant fixation in the presence of a natural enemy
Abstract The literature about mutant invasion and fixation typically assumes populations to exist in isolation from their ecosystem. Yet, populations are part of ecological communities, and enemy-victim (e.g. predator-prey or pathogen-host) interactions are particularly common. We use spatially explicit, computational pathogen-host models (with wild-type and mutant hosts) to re-visit the established theory about mutant fixation, where the pathogen equally attacks both wild-type and mutant individuals. Mutant fitness is assumed to be unrelated to infection. We find that pathogen presence substantially weakens selection, increasing the fixation probability of disadvantageous mutants and decreasing it for advantageous mutants. The magnitude of the effect rises with the infection rate. This occurs because infection induces spatial structures, where mutant and wild-type individuals are mostly spatially separated. Thus, instead of mutant and wild-type individuals competing with each other, it is mutant and wild-type “patches” that compete, resulting in smaller fitness differences and weakened selection. This implies that the deleterious mutant burden in natural populations might be higher than expected from traditional theory.
more »
« less
- Award ID(s):
- 2152155
- PAR ID:
- 10470021
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 14
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Xanthomonas perforans is a seed-borne hemi-biotrophic pathogen that successfully establishes infection in the phyllosphere of tomato. While the majority of the studies investigating mechanistic basis of pathogenesis have focused on successful apoplastic growth, factors important during asymptomatic colonization in the early stages of disease development are not well understood. In this study, we show that tssM gene of the type VI secretion system cluster i3* (T6SS-i3*) plays a significant role during initial asymptomatic epiphytic colonization at different stages during the life cycle of the pathogen. Mutation in a core gene, tssM of T6SS-i3*, imparted higher aggressiveness to the pathogen, as indicated by higher overall disease severity, higher in planta growth as well as shorter latent infection period compared to the wild-type upon dip-inoculation of 4-5-week-old tomato plants. Contribution of tssM towards aggressiveness was evident during vertical transmission from seed-to-seedling with wild-type showing reduced disease severity as well as lower in planta populations on seedlings compared to the mutant. Presence of functional TssM offered higher epiphytic fitness as well as higher dissemination potential to the pathogen when tested in an experimental setup mimicking transplant house high-humidity conditions. We showed higher osmotolerance being one mechanism by which TssM offers higher epiphytic fitness. Taken together, these data reveal that functional TssM plays a larger role in offering ecological advantage to the pathogen. TssM prolongs the association of hemi-biotrophic pathogen with the host, minimizing overall disease severity, yet facilitating successful dissemination.more » « less
-
ABSTRACT We study the fixation probability for two versions of the Moran process on the random graph at the threshold for connectivity. The Moran process models the spread of a mutant population in a network. Throughout the process, there are vertices of two types, mutants, and non‐mutants. Mutants have fitness and non‐mutants have fitness 1. The process starts with a unique individual mutant located at the vertex . In the Birth‐Death version of the process a random vertex is chosen proportionally to its fitness and then changes the type of a random neighbor to its own. The process continues until the set of mutants is empty or . In the Death‐Birth version, a uniform random vertex is chosen and then takes the type of a random neighbor, chosen according to fitness. The process again continues until the set of mutants is empty or . Thefixation probabilityis the probability that the process ends with . We show that asymptotically correct estimates of the fixation probability depend only on the degree of and its neighbors. In some cases we can provide values for these estimates and in other places we can only provide non‐linear recurrences that could be used to compute values.more » « less
-
Abstract While the negative effects that pathogens have on their hosts are well-documented in humans and agricultural systems, direct evidence of pathogen-driven impacts in wild host populations is scarce and mixed. Here, to determine how the strength of pathogen-imposed selection depends on spatial structure, we analyze growth rates across approximately 4000 host populations of a perennial plant through time coupled with data on pathogen presence-absence. We find that infection decreases growth more in the isolated than well-connected host populations. Our inoculation study reveals isolated populations to be highly susceptible to disease while connected host populations support the highest levels of resistance diversity, regardless of their disease history. A spatial eco-evolutionary model predicts that non-linearity in the costs to resistance may be critical in determining this pattern. Overall, evolutionary feedbacks define the ecological impacts of disease in spatially structured systems with host gene flow being more important than disease history in determining the outcome.more » « less
-
Abstract Symbiotic interactions can determine the evolutionary trajectories of host species, influencing genetic variation through selection and changes in demography. In the context of strong selective pressures such as those imposed by infectious diseases, symbionts providing defences could contribute to increase host fitness upon pathogen emergence. Here, we generated genome‐wide data of an amphibian species to find evidence of evolutionary pressures driven by two skin symbionts: a batrachochytrid fungal pathogen and an antifungal bacterium. Using demographic modelling, we found evidence of decreased effective population size, probably due to pathogen infections. Additionally, we investigated host genetic associations with infection status, antifungal bacterium abundance and overall microbiome diversity using structural equation models. We uncovered relatively lower nucleotide diversity in infected frogs and potential heterozygote advantage to recruit the candidate beneficial symbiont and fight infections. Our models indicate that environmental conditions have indirect effects on symbiont abundance through both host body traits and microbiome diversity. Likewise, we uncovered a potential offsetting effect among host heterozygosity–fitness correlations, plausibly pointing to different ecological and evolutionary processes among the three species due to dynamic interactions. Our findings revealed that evolutionary pressures not only arise from the pathogen but also from the candidate beneficial symbiont, and both interactions shape the genetics of the host. Our results advance knowledge about multipartite symbiotic relationships and provide a framework to model ecological and evolutionary dynamics in wild populations. Finally, our study approach can be applied to inform conservation actions such as bioaugmentation strategies for other imperilled amphibians affected by infectious diseases.more » « less
