Ben Ashby

The diversity-generating benefits of a prokaryotic adaptive immune system

Prokaryotic CRISPR-Cas adaptive immune systems insert spacers derived from viruses and other parasitic DNA elements into CRISPR loci to provide sequence-specific immunity. This frequently results in high within-population spacer diversity, but it is unclear if and why this is important. Here we show that, as a result of this spacer diversity, viruses can no longer evolve to overcome CRISPR-Cas by point mutation, which results in rapid virus extinction. This effect arises from synergy between spacer diversity and the high specificity of infection, which greatly increases overall population resistance. We propose that the resulting short-lived nature of CRISPR-dependent bacteria–virus coevolution has provided strong selection for the evolution of sophisticated virus-encoded anti-CRISPR mechanisms.

Population mixing promotes arms race host–parasite coevolution

The consequences of host–parasite coevolution are highly contingent on the qualitative coevolutionary dynamics: whether selection fluctuates (fluctuating selection dynamic; FSD), or is directional towards increasing infectivity/resistance (arms race dynamic; ARD). Both genetics and ecology can play an important role in determining whether coevolution follows FSD or ARD, but the ecological conditions under which FSD shifts to ARD, and vice versa, are not well understood. The degree of population mixing is thought to increase host exposure to parasites, hence selecting for greater resistance and infectivity ranges, and we hypothesize this promotes ARD. We tested this by coevolving bacteria and viruses in soil microcosms and found that population mixing shifted bacteria–virus coevolution from FSD to ARD. A simple theoretical model produced qualitatively similar results, showing that mechanisms that increase host exposure to parasites tend to push dynamics towards ARD. The shift from FSD to ARD with increased population mixing may help to explain variation in coevolutionary dynamics between different host–parasite systems, and more specifically the observed discrepancies between laboratory and field bacteria–virus coevolutionary studies.

Sexually transmitted infections in polygamous mating systems

Sexually transmitted infections (STIs) are often associated with chronic diseases and can have severe impacts on host reproductive success. For airborne or socially transmitted pathogens, patterns of contact by which the infection spreads tend to be dispersed and each contact may be of very short duration. By contrast, the transmission pathways for STIs are usually characterized by repeated contacts with a small subset of the population. Here we review how heterogeneity in sexual contact patterns can influence epidemiological dynamics, and present a simple model of polygyny/polyandry to illustrate the impact of biased mating systems on disease incidence and pathogen virulence.

Pathogen selection drives nonoverlapping associations between HLA loci

Significance Human leukocyte antigens (HLA), first identified in tissue-matching for transplantation, play a critical role in immunity. HLAs are extraordinarily diverse, but certain sets of HLA genes are more likely to be found together than others. Here, we show that associations between HLA genes can arise through their coevolutionary interaction with pathogens. Technological advances are making it easier to determine HLA types, but DNA sequence alone cannot fully predict an HLA’s functional properties. Our work offers a new evolutionary approach to tackling this problem. Pathogen-mediated selection is commonly invoked as an explanation for the exceptional polymorphism of the HLA gene cluster, but its role in generating and maintaining linkage disequilibrium between HLA loci is unclear. Here we show that pathogen-mediated selection can promote nonrandom associations between HLA loci. These associations may be distinguished from linkage disequilibrium generated by other population genetic processes by virtue of being nonoverlapping as well as nonrandom. Within our framework, immune selection forces the pathogen population to exist as a set of antigenically discrete strains; this then drives nonoverlapping associations between the HLA loci through which recognition of these antigens is mediated. We demonstrate that this signature of pathogen-driven selection can be observed in existing data, and propose that analyses of HLA population structure can be combined with laboratory studies to help us uncover the functional relationships between HLA alleles. In a wider coevolutionary context, our framework also shows that the inclusion of memory immunity can lead to robust cyclical dynamics across a range of host–pathogen systems.

Coevolution of parasite virulence and host mating strategies.

Significance It is well understood that parasitism may help to explain the evolution of mating strategies, but host behavior is, in turn, critical to the transmission and therefore the evolution of parasites. Despite this clear reciprocity, we lack a coevolutionary theory of mate choice and parasite virulence. We show how coevolution leads to a wide range of dynamics, including cycling and stable strategies, and that this resolves a key criticism of the role of parasites in mate choice: that parasites will evolve to be avirulent, thus reducing their impact on mating strategies. Coevolution also leads to new predictions for the role of several host and parasite traits on selection for mate choice that will guide future experimental and comparative work. Parasites are thought to play an important role in sexual selection and the evolution of mating strategies, which in turn are likely to be critical to the transmission and therefore the evolution of parasites. Despite this clear interdependence we have little understanding of parasite-mediated sexual selection in the context of reciprocal parasite evolution. Here we develop a general coevolutionary model between host mate preference and the virulence of a sexually transmitted parasite. We show when the characteristics of both the host and parasite lead to coevolutionarily stable strategies or runaway selection, and when coevolutionary cycling between high and low levels of host mate choosiness and virulence is possible. A prominent argument against parasites being involved in sexual selection is that they should evolve to become less virulent when transmission depends on host mating success. The present study, however, demonstrates that coevolution can maintain stable host mate choosiness and parasite virulence or indeed coevolutionary cycling of both traits. We predict that choosiness should vary inversely with parasite virulence and that both relatively long and short life spans select against choosy behavior in the host. The model also reveals that hosts can evolve different behavioral responses from the same initial conditions, which highlights difficulties in using comparative analysis to detect parasite-mediated sexual selection. Taken as a whole, our results emphasize the importance of viewing parasite-mediated sexual selection in the context of coevolution.

Spatial structure mitigates fitness costs in host-parasite coevolution.

The extent of population mixing is known to influence the coevolutionary outcomes of many host and parasite traits, including the evolution of generalism (the ability to resist or infect a broad range of genotypes). While the segregation of populations into interconnected demes has been shown to influence the evolution of generalism, the role of local interactions between individuals is unclear. Here, we combine an individual-based model of microbial communities with a well-established framework of genetic specificity that matches empirical observations of bacterium-phage interactions. We find the evolution of generalism in well-mixed populations to be highly sensitive to the severity of associated fitness costs, but the constraining effect of costs on the evolution of generalism is lessened in spatially structured populations. The contrasting outcomes between the two environments can be explained by different scales of competition (i.e., global vs. local). These findings suggest that local interactions may have important effects on the evolution of generalism in host-parasite interactions, particularly in the presence of high fitness costs.

Parasitic castration promotes coevolutionary cycling but also imposes a cost on sex.

Antagonistic coevolution between hosts and parasites is thought to drive a range of biological phenomena including the maintenance of sexual reproduction. Of particular interest are conditions that produce persistent fluctuations in the frequencies of genes governing host–parasite specificity (coevolutionary cycling), as sex may be more beneficial than asexual reproduction in a constantly changing environment. Although many studies have shown that coevolutionary cycling can lead to the maintenance of sex, the effects of ecological feedbacks on the persistence of these fluctuations in gene frequencies are not well understood. Here, we use a simple deterministic model that incorporates ecological feedbacks to explore how parasitic reductions in host fecundity affect the maintenance of coevolutionary cycling. We demonstrate that parasitic castration is inherently destabilizing and may be necessary for coevolutionary cycling to persist indefinitely, but also reduces the likelihood that sexually reproducing individuals will find a fertile partner, which may select against sex. These findings suggest that castrators can play an important role in shaping host evolution and are likely to be good targets for observing fluctuations in gene frequencies that govern specificity in host–parasite interactions.

Diversity and the maintenance of sex by parasites

The Red Queen hypothesis (RQH) predicts that parasite‐mediated selection will maintain sexual individuals in the face of competition from asexual lineages. The prediction is that sexual individuals will be difficult targets for coevolving parasites if they give rise to more genetically diverse offspring than asexual lineages. However, increasing host genetic diversity is known to suppress parasite spread, which could provide a short‐term advantage to clonal lineages and lead to the extinction of sex. We test these ideas using a stochastic individual‐based model. We find that if parasites are readily transmissible, then sex is most likely to be maintained when host diversity is high, in agreement with the RQH. If transmission rates are lower, however, we find that sexual populations are most likely to persist for intermediate levels of diversity. Our findings thus highlight the importance of genetic diversity and its impact on epidemiological dynamics for the maintenance of sex by parasites.

Effects of epistasis on infectivity range during host-parasite coevolution

Understanding how parasites adapt to changes in host resistance is crucial to evolutionary epidemiology. Experimental studies have demonstrated that parasites are more capable of adapting to gradual, rather than sudden changes in host phenotype, as the latter may require multiple mutations that are unlikely to arise simultaneously. A key, but as yet unexplored factor is precisely how interactions between mutations (epistasis) affect parasite evolution. Here, we investigate this phenomenon in the context of infectivity range, where parasites may experience selection to infect broader sets of genotypes. When epistasis is strongly positive, we find that parasites are unlikely to evolve broader infectivity ranges if hosts exhibit sudden, rather than gradual changes in phenotype, in close agreement with empirical observations. This is due to a low probability of fixing multiple mutations that individually confer no immediate advantage. When epistasis is weaker, parasites are more likely to evolve broader infectivity ranges if hosts make sudden changes in phenotype, which can be explained by a balance between mutation supply and selection. Thus, we demonstrate that both the rate of phenotypic change in hosts and the form of epistasis between mutations in parasites are crucial in shaping the evolution of infectivity range.

Friendly foes: The evolution of host protection by a parasite

Hosts are often infected by multiple parasite species, yet the ecological and evolutionary implications of the interactions between hosts and coinfecting parasites are largely unknown. Most theoretical models of evolution among coinfecting parasites focus on the evolution of virulence, but parasites may also evolve to protect their hosts by reducing susceptibility (i.e., conferring resistance) to other parasites or reducing the virulence of coinfecting parasites (i.e., conferring tolerance). Here, we analyze the eco‐evolutionary dynamics of parasite‐conferred resistance and tolerance using coinfection models. We show that both parasite‐conferred resistance and tolerance can evolve for a wide range of underlying trade‐offs. The shape and strength of the trade‐off qualitatively affects the outcome causing shifts between the minimisation or maximization of protection, intermediate stable strategies, evolutionary branching, and bistability. Furthermore, we find that a protected dimorphism can readily evolve for parasite‐conferred resistance, but find no evidence of evolutionary branching for parasite‐conferred tolerance, in general agreement with previous work on host evolution. These results provide novel insights into the evolution of parasite‐conferred resistance and tolerance, and suggest clues to the underlying trade‐offs in recent experimental work on microbe‐mediated protection. More generally, our results highlight the context dependence of host‐parasite relationships in complex communities.