Variability in fitness effects can preclude selection of the fittest.

Evolutionary biologists often predict the outcome of natural selection on an allele by measuring its effects on lifetime survival and reproduction of individual carriers. However, alleles affecting traits like sex, evolvability, and cooperation can cause fitness effects that depend heavily on differences in the environmental, social, and genetic context of individuals carrying the allele. This variability makes it difficult to summarize the evolutionary fate of an allele based solely on its effects on any one individual. Attempts to average over this variability can sometimes salvage the concept of fitness. In other cases evolutionary outcomes can only be predicted by considering the entire genealogy of an allele, thus limiting the utility of individual fitness altogether. We describe a number of intriguing new evolutionary phenomena that have emerged in studies that explicitly model long-term lineage dynamics and discuss implications for the evolution of infectious diseases.

Functional Responses of Salt Marsh Microbial Communities to Long-Term Nutrient Enrichment.

UNLABELLED: Environmental nutrient enrichment from human agricultural and waste runoff could cause changes to microbial communities that allow them to capitalize on newly available resources. Currently, the response of microbial communities to nutrient enrichment remains poorly understood, and, while some studies have shown no clear changes in community composition in response to heavy nutrient loading, others targeting specific genes have demonstrated clear impacts. In this study, we compared functional metagenomic profiles from sediment samples taken along two salt marsh creeks, one of which was exposed for more than 40 years to treated sewage effluent at its head. We identified strong and consistent increases in the relative abundance of microbial genes related to each of the biochemical steps in the denitrification pathway at enriched sites. Despite fine-scale local increases in the abundance of denitrification-related genes, the overall community structures based on broadly defined functional groups and taxonomic annotations were similar and varied with other environmental factors, such as salinity, which were common to both creeks. Homology-based taxonomic assignments of nitrous oxide reductase sequences in our data show that increases are spread over a broad taxonomic range, thus limiting detection from taxonomic data alone. Together, these results illustrate a functionally targeted yet taxonomically broad response of microbial communities to anthropogenic nutrient loading, indicating some resolution to the apparently conflicting results of existing studies on the impacts of nutrient loading in sediment communities. IMPORTANCE: In this study, we used environmental metagenomics to assess the response of microbial communities in estuarine sediments to long-term, nutrient-rich sewage effluent exposure. Unlike previous studies, which have mainly characterized communities based on taxonomic data or primer-based amplification of specific target genes, our whole-genome metagenomics approach allowed an unbiased assessment of the abundance of denitrification-related genes across the entire community. We identified strong and consistent increases in the relative abundance of gene sequences related to denitrification pathways across a broad phylogenetic range at sites exposed to long-term nutrient addition. While further work is needed to determine the consequences of these community responses in regulating environmental nutrient cycles, the increased abundance of bacteria harboring denitrification genes suggests that such processes may be locally upregulated. In addition, our results illustrate how whole-genome metagenomics combined with targeted hypothesis testing can reveal fine-scale responses of microbial communities to environmental disturbance.

Natural selection promotes antigenic evolvability.

The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

First arrived takes all: inhibitory priority effects dominate competition between co-infecting Borrelia burgdorferi strains.

BACKGROUND: Within-host microbial communities and interactions among microbes are increasingly recognized as important factors influencing host health and pathogen transmission. The microbial community associated with a host is indeed influenced by a complex network of direct and indirect interactions between the host and the lineages of microbes it harbors, but the mechanisms are rarely established. We investigated the within-host interactions among strains of Borrelia burgdorferi, the causative agent of Lyme disease, using experimental infections in mice. We used a fully crossed-design with three distinct strains, each group of hosts receiving two sequential inoculations. We used data from these experimental infections to assess the effect of coinfection on bacterial dissemination and fitness (by measuring the transmission of bacteria to xenodiagnostic ticks) as well as the effect of coinfection on host immune response compared to single infection. RESULTS: The infection and transmission data strongly indicate a competitive interaction among B. burgdorferi strains within a host in which the order of appearance of the strain is the main determinant of the competitive outcome. This pattern is well described by the classic priority effect in the ecological literature. In all cases, the primary strain a mouse was infected with had an absolute fitness advantage primarily since it was transmitted an order of magnitude more than the secondary strain. The mechanism of exclusion of the secondary strain is an inhibition of the colonization of mouse tissues, even though 29% of mice showed some evidence of infection by secondary strain. Contrary to expectation, the strong and specific adaptive immune response evoked against the primary strain was not followed by production of immunoglobulins after the inoculation of the secondary strain, neither against strain-specific antigen nor against antigens common to all strains. Hence, the data do not support a major role of the immune response in the observed priority effect. CONCLUSION: The strong inhibitory priority effect is a dominant mechanism underlying competition for transmission between coinfecting B. burgdorferi strains, most likely through resource exploitation. The observed priority effect could shape bacterial diversity in nature, with consequences in epidemiology and evolution of the disease.

Reductions in human Lyme disease risk due to the effects of oral vaccination on tick-to-mouse and mouse-to-tick transmission.

Vaccinating wildlife is becoming an increasingly popular method to reduce human disease risks from pathogens such as Borrelia burgdorferi, the causative agent of Lyme disease. To successfully limit human disease risk, vaccines targeting the wildlife reservoirs of B. burgdorferi must be easily distributable and must effectively reduce pathogen transmission from infected animals, given that many animals in nature will be infected prior to vaccination. We assessed the efficacy of an easily distributable oral bait vaccine based on the immunogenic outer surface protein A (OspA) to protect uninfected mice from infection and to reduce transmission from previously infected white-footed mice, an important reservoir host of B. burgdorferi. Oral vaccination of white-footed mice effectively reduces transmission of B. burgdorferi at both critical stages of the Lyme disease transmission cycle. First, oral vaccination of uninfected white-footed mice elicits an immune response that protects mice from B. burgdorferi infection. Second, oral vaccination of previously infected mice significantly reduces the transmission of B. burgdorferi to feeding ticks despite a statistically nonsignificant immune response. We used the estimates of pathogen transmission to and from vaccinated and unvaccinated mice to model the efficacy of an oral vaccination campaign targeting wild white-footed mice. Projection models suggest that the effects of the vaccine on both critical stages of the transmission cycle of B. burgdorferi act synergistically in a positive feedback loop to reduce the nymphal infection prevalence, and thus human Lyme disease risk, well below what would be expected from either effect alone. This study suggests that oral immunization of wildlife with an OspA-based vaccine can be a promising long-term strategy to reduce human Lyme disease risk.

Intergenerational effect of juvenile hormone on offspring in Pogonomyrmex harvester ants.

Parents can influence the phenotypes of their offspring via a number of mechanisms. In harvester ants, whether female progeny develop into workers or daughter queens is strongly influenced by the age and temperature conditions experienced by their mother, which is associated with variation in maternal ecdysteroid deposition in fertilized eggs. In many insects, juvenile hormone (JH) is antagonistic to ecdysteroid release, suggesting that seasonal and age-based variation in maternal JH titers may explain maternal effects on offspring size and reproductive caste. To test this hypothesis, we artificially increased maternal JH titers with methoprene, a JH analog, in laboratory colonies of two Pogonomyrmex populations exhibiting genetic caste determination. Increasing maternal JH resulted in a 50% increase in worker body size, as well as a sharp reduction in total number of progeny reared, but did not alter the genotype of progeny reared to adulthood. The intergenerational effect of JH manipulation was not mediated by a reduction in ecdysteroid deposition into eggs; instead, changes in egg size, trophic egg availability or brood/worker ratio may have altered the nutritional environment of developing larvae. Egg ecdysteroid content was significantly negatively correlated with natural variation in worker body size, however, suggesting that there are multiple independent routes by which queens can modify offspring phenotypes.