Role of Evolved Host Breadth in the Initial Emergence of an Rna Virus

Abstract

Understanding how evolution promotes pathogen emergence would aid disease management, and prediction of future host shifts. Increased pathogen infectiousness of different hosts may occur through direct selection, or fortuitously via indirect selection. However, it is unclear which type of selection tends to produce host breadth promoting pathogen emergence. We predicted that direct selection for host breadth should foster emergence by causing higher population growth on new hosts, lower amongpopulation variance in growth on new hosts, and lower population variance in growth across new hosts. We tested the predictions using experimentally evolved vesicular stomatitis virus populations, containing groups of host-use specialists, directly selected generalists, and indirectly selected generalists. In novel-host challenges, viruses directly selected for generalism showed relatively higher or equivalent host growth, lower among-population variance in host growth, and lower population variance in growth across hosts. Thus, two of three outcomes supported our prediction that directly selected host breadth should favor host colonization. Also, we observed that indirectly selected generalists were advantaged over specialist viruses, indicating that fortuitous changes in host breadth may also promote emergence. We discuss evolution of phenotypic plasticity versus environmental robustness in viruses, virus avoidance of extinction, and surveillance of pathogen niche breadth to predict future likelihood of emergence.K E Y W O R D S : Experimental evolution, generalist, host shift, niche expansion, specialist, vesicular stomatitis virus.

Host Alternation of Chikungunya Virus Increases Fitness while Restricting Population Diversity and Adaptability to Novel Selective Pressures

“…During alternating passage, selection may be focused on maintaining replication competence in both hosts, by favoring generalist genomes of relatively high fitness for both cell types (49). In this case, maximum genetic diversity may not be reached, as minority mutations that would drift the mutant spectrum away from overlapping regions of invertebrate and vertebrate sequence space would be removed by purifying selection with each alternating passage.…”

Understanding specialism when the jack of all trades can be the master of all

“…First they arise in populations exposed to temporally variable habitats, when purifying selection can act to purge environment-specific deleterious mutations. Second, they arise in populations evolving in one or a few environments when conditionally deleterious mutations fail to arise stochastically [10]. Unlike under directional selection, where generalists have a slower sojourn time to high fitness in the environment shared with the specialist [38] (figure 3a), under mutation accumulation there need not be a difference in the rate of fitness gains in the shared environment for parallel evolving populations of specialists and generalists because the adaptive alleles being fixed in the two types of populations are the same ( figure 3b,d).…”

“…In this example of epistatic pleiotropy, cost-free generalists can arise in three ways, depending on the environments to which populations are exposed, and on the order in which mutations arise [10]. First, in populations beginning at genotype ab in a temporally variable habitat, purifying selection will purge mutations to aB, maintaining ab in the population until the cost-free generalist Ab arises and can become fixed.…”

On the possible role of robustness in the evolution of infectious diseases

“…49,50 The formal prediction was that VSV populations experiencing direct selection for host range would have higher mean growth and less variance in mean growth on a collection of challenge hosts, compared to VSV populations that were either relatively specialized or indirectly selected for host range. 51 When challenged to grow on four novel hosts in vitro, the viruses that had been selected for generalism exhibited higher or equivalent host growth, lower among-population variance in host growth, and lower variance in population growth across hosts. Thus, these three predictions relating to the hypothesis were generally supported because direct selection for host breadth more often allowed successful emergence.…”

“…The results suggested that determination of current niche breadth should be further investigated as a potentially useful indicator in predicting pathogen emergence. 51,52 Because these many recent empirical breakthroughs in the study of robustness have involved microbes, one might predict that infectious disease is the primary biomedical realm where these robustness results might have an immediate, practical impact. Below we describe three examples of biomedically important human disease systems where robustness theory appears highly relevant.…”