Kayla C. King

Does genetic diversity limit disease spread in natural host populations

It is a commonly held view that genetically homogenous host populations are more vulnerable to infection than genetically diverse populations. The underlying idea, known as the ‘monoculture effect,’ is well documented in agricultural studies. Low genetic diversity in the wild can result from bottlenecks (that is, founder effects), biparental inbreeding or self-fertilization, any of which might increase the risk of epidemics. Host genetic diversity could buffer populations against epidemics in nature, but it is not clear how much diversity is required to prevent disease spread. Recent theoretical and empirical studies, particularly in Daphnia populations, have helped to establish that genetic diversity can reduce parasite transmission. Here, we review the present theoretical work and empirical evidence, and we suggest a new focus on finding ‘diversity thresholds.’

Running with the Red Queen: the role of biotic conflicts in evolution

What are the causes of natural selection? Over 40 years ago, Van Valen proposed the Red Queen hypothesis, which emphasized the primacy of biotic conflict over abiotic forces in driving selection. Species must continually evolve to survive in the face of their evolving enemies, yet on average their fitness remains unchanged. We define three modes of Red Queen coevolution to unify both fluctuating and directional selection within the Red Queen framework. Empirical evidence from natural interspecific antagonisms provides support for each of these modes of coevolution and suggests that they often operate simultaneously. We argue that understanding the evolutionary forces associated with interspecific interactions requires incorporation of a community framework, in which new interactions occur frequently. During their early phases, these newly established interactions are likely to drive fast evolution of both parties. We further argue that a more complete synthesis of Red Queen forces requires incorporation of the evolutionary conflicts within species that arise from sexual reproduction. Reciprocally, taking the Red Queens perspective advances our understanding of the evolution of these intraspecific conflicts.

Rapid evolution of microbe-mediated protection against pathogens in a worm host.

Microbes can defend their host against virulent infections, but direct evidence for the adaptive origin of microbe-mediated protection is lacking. Using experimental evolution of a novel, tripartite interaction, we demonstrate that mildly pathogenic bacteria (Enterococcus faecalis) living in worms (Caenorhabditis elegans) rapidly evolved to defend their animal hosts against infection by a more virulent pathogen (Staphylococcus aureus), crossing the parasitism–mutualism continuum. Host protection evolved in all six, independently selected populations in response to within-host bacterial interactions and without direct selection for host health. Microbe-mediated protection was also effective against a broad spectrum of pathogenic S. aureus isolates. Genomic analysis implied that the mechanistic basis for E. faecalis-mediated protection was through increased production of antimicrobial superoxide, which was confirmed by biochemical assays. Our results indicate that microbes living within a host may make the evolutionary transition to mutualism in response to pathogen attack, and that microbiome evolution warrants consideration as a driver of infection outcome.

PARASITES, SEX, AND CLONAL DIVERSITY IN NATURAL SNAIL POPULATIONS

Under the Red Queen hypothesis, host–parasite coevolution selects against common host genotypes. Although this mechanism might underlie the persistence of sexual reproduction, it might also maintain high clonal diversity. Alternatively, clonal diversity might be maintained by multiple origins of parthenogens from conspecific sexuals, a feature in many animal groups. Herein, we addressed the maintenance of overall genetic diversity by coevolving parasites, as predicted by the Red Queen hypothesis. We specifically examined the contribution of parasites to host clonal diversity and the frequency of sexually reproducing individuals in natural stream populations of Potamopyrgus antipodarum snails. We also tested the alternative hypothesis that clonal diversity is maintained by the input of clones by mutation from sympatric sexuals. Clonal diversity and the frequency of sexual individuals were both positively related to infection frequency. Surprisingly, although clones are derived by mutation from sexual snails, parasites explained more of the genotypic variation among parthenogenetic subpopulations. Our findings thus highlight the importance of parasites as drivers of clonal diversity, as well as sex.

Hybridization in parasites: consequences for adaptive evolution, pathogenesis, and public health in a changing world.

Hybridization of parasites is an emerging public health concern at the interface of infectious disease biology and evolution. Increasing economic development, human migration, global trade, and climate change are all shifting the geographic distribution of existing human, livestock, companion animal, and wildlife parasites [1–9]. As a result, human populations encounter new infections more frequently, and coinfection by multiple parasites from different lineages or species within individual hosts occurs. Coinfection may have a large impact on the hosts and parasites involved, often as a result of synergistic or antagonistic interactions between parasites [10]. Indeed, mixed-species coinfections have been found to influence parasite establishment, growth, maturation, reproductive success, and/or drug efficacy [11–13]. However, coinfections can allow for heterospecific (between-species or between-lineage) mate pairings, resulting in parthenogenesis (asexual reproduction in which eggs occur without fertilization), introgression (the introduction of single genes or chromosomal regions from one species into that of another through repeated backcrossing), and whole-genome admixture through hybridization [14].

Trematode parasites infect or die in snail hosts

The Red Queen hypothesis is based on the assumption that parasites must genetically match their hosts to infect them successfully. If the parasites fail, they are assumed to be killed by the hosts immune system. Here, we tested this using sympatric (mostly susceptible) and allopatric (mostly resistant) populations of a freshwater snail and its trematode parasite. We determined whether parasites which do not infect are either killed or passed through the hosts digestive tract and remain infectious. Our results show that parasites do not get a second chance: they either infect or are killed by the host. The results suggest strong selection against parasites that are not adapted to local host genotypes.

Beyond killing: Can we find new ways to manage infection?

The antibiotic pipeline is running dry and infectious disease remains a major threat to public health. An efficient strategy to stay ahead of rapidly adapting pathogens should include approaches that replace, complement or enhance the effect of both current and novel antimicrobial compounds. In recent years, a number of innovative approaches to manage disease without the aid of traditional antibiotics and without eliminating the pathogens directly have emerged. These include disabling pathogen virulence-factors, increasing host tissue damage control or altering the microbiota to provide colonization resistance, immune resistance or disease tolerance against pathogens. We discuss the therapeutic potential of these approaches and examine their possible consequences for pathogen evolution. To guarantee a longer half-life of these alternatives to directly killing pathogens, and to gain a full understanding of their population-level consequences, we encourage future work to incorporate evolutionary perspectives into the development of these treatments.

Harnessing the Power of Defensive Microbes: Evolutionary Implications in Nature and Disease Control.

Microbes are vital to the functioning of multicellular organisms. This realisation has fuelled great interest in the effects of microbes on the health of plant [1–3] and animal hosts [4–6] and has revealed that microbe-mediated protection against infectious disease is a widespread phenomenon (Table 1) [7–11]. Defensive microbes can protect hosts from infection by parasites (including pathogens and parasitoids) by direct or host-mediated means (Box 1). Such protective traits have made these microbes attractive candidates for disease control. In fact, defensive microbes are already being applied in phage therapy and bacteriotherapy for humans, as well as to control vector-borne and agricultural diseases (Table 2). Box 1. Mechanisms of Defensive Microbes Direct Hyperparasitism or predation: Microbes can parasitise or predate upon the parasite [39]. Interference competition: Microbes can produce toxic compounds, such as antibiotics or bacteriocins, that may either kill the parasite or reduce its growth rate [40–42]. Resource competition: Microbes can compete with parasites for host resources [10,42], usually via the rate of resource acquisition [40,41]. Host-mediated Host immune-mediation: Microbes can elicit a host immune response to which the parasite is not resistant [40,42]. Host tolerance-mediation: Microbes can increase the fitness of their host during infection without reducing the fitness of the parasite by enhancing host tolerance (e.g., via tissue damage prevention and/or repair) [43,44]. Table 1 Defensive microbes in nature. Table 2 Applications of defensive microbes in infectious disease control. Despite the impact defensive microbes can have on host and parasite fitness, our current perspective of host–parasite evolution is largely based upon pairwise species interactions [12]. By combining knowledge of defensive microbe–parasite interactions at the mechanistic level with evolutionary theory, we can predict how defensive microbes might alter the evolution of host and parasite traits, such as resistance and virulence. This will not only shape how we understand patterns of host–parasite coevolution in nature but will inform our decisisons in utilising defensive microbes as disease control agents. We propose three potential evolutionary implications of defensive microbes on host–parasite interactions.

Virulence, cultivating conditions, and phylogenetic analyses of oomycete parasites in Daphnia.

We describe the infectivity, virulence, cultivating conditions, and phylogenetic positions of naturally occurring oomycete parasites of Daphnia, invertebrates which play a major role in aquatic food webs. Daphnia pulex individuals were found dead and covered by oomycete mycelia when exposed to pond sediments. We were able to extract 4 oomycete isolates from dead Daphnia and successfully cultivate them. Using the ITS and LSU rDNA sequences, we further showed these isolates to be distinct species. The isolates were experimentally demonstrated to be parasitic and not saprobic. After exposure to the parasites, Daphnia mortality was much higher than that reported for Daphnia infected with other known parasite species. Therefore, it is likely that oomycete parasites are important selective pressures in natural Daphnia populations. Moreover, their close phylogenetic relationship to parasites of fish and algae suggests that the stability of aquatic food webs (i.e. fish-Daphnia-algae) might be influenced by the shared parasite communities.

The Geographic Mosaic of Sex and Infection in Lake Populations of a New Zealand Snail at Multiple Spatial Scales

Understanding how sexual and asexual forms of the same species coexist is a challenge for evolutionary biology. The Red Queen hypothesis predicts that sex is favored by parasite-mediated selection against common asexual genotypes, leading to the coexistence of sexual and asexual hosts. In a geographic mosaic, where the risk of infection varies in space, the theory also predicts that sexual reproduction would be positively correlated with disease prevalence. We tested this hypothesis in lake populations of a New Zealand freshwater snail, Potamopyrgus antipodarum, by comparing pairwise difference matrices for infection frequency and male frequency using partial Mantel tests. We conducted the test at three spatial scales: among lakes on the South Island, among depths within an intensively sampled lake (Lake Alexandrina), and within depths at Lake Alexandrina. We found that the difference in infection risk and the difference in the proportion of sexual snails were significantly and positively correlated at all spatial scales. Our results thus suggest that parasite-mediated selection contributes to the long-term coexistence of sexual and asexual individuals in coevolutionary hotspots, and that the “warmth” of hotspots can vary on small spatial scales.