Steven A. Frank

Models of Parasite Virulence

Several evolutionary processes influence virulence, the amount of damage a parasite causes to its host. For example, parasites are favored to exploit their hosts prudently to prolong infection and avoid killing the host. Parasites also need to use some host resources to reproduce and transmit infections to new hosts. Thus parasites face a tradeoff between prudent exploitation and rapid reproduction -a life history tradeoff between logevity and fecundity. Other tradeoffs among components of parasite fitness also influence virulence. For example, competition among parasite genotypes favors rapid growth to achieve greater relative success within the host. Rapid growth may, however, lower the total productivity of the local group by overexploiting the host, which is a potentially renewable food suply. This is a problem of kin selection and group selection. I summarize models of parasite virulence with the theoretical tools of life history analysis, kin selection, and epidemiology. I then apply the theory to recent empirical studies and models of virulence. These applications, to nematodes, to the extreme virulence of hospital epidemics, and to bacterial meningitis, show the power of simple life history theory to highlight interesting questions and to provide a rich array of hypotheses. These examples also show the kinds of conceptual mistakes that commonly arise when only a few components of parasite fitness are analysed in isolation. The last part of the article connects standard models of parasite virulence to diverse topics, such as the virulence of bacterial plasmids, the evolution of genomes, and the processes that influence conflict and cooperation among the earliest replicators near the origin of life.

THE EVOLUTIONARY DYNAMICS OF CYTOPLASMIC MALE STERILITY

Cytoplasmic male sterility (CMS) is the maternal transmission of failed pollen production in hermaphroditic plants leading to a mixture of male-sterile and hermaphroditic individuals in the population (gynodioecy). Autosomal genes that can restore pollen fertility in the presence of male-sterile cytotypes are commonly observed. CMS in wild populations tends to be associated with (1) the maintenance of distinct cytotypes, each capable of causing male sterility by an apparently different mechanism since each is susceptible to only a particular subset of autosomal restorer alleles; (2) the maintenance of polymorphism at several autosomal restorer loci, with particular alleles or loci specialized for restoring pollen fertility when associated with particular cytotypes; (3) the maintenance of genetic differentiation among geographically distant populations; and (4) the maintenance of phenotypic diversity among populations, measured as the percentage of malesterile individuals. Observations and previous theoretical explanations were reviewed. A simulation model was then constructed, and the results of the simulations appear to be consistent with the evolutionary dynamics and patterns of genetic polymorphism inferred from wild populations. In the simulation models, when cytoplasmic male-sterility alleles are present and their associated autosomal pollen-restorer alleles are absent (cytoplasmic control), the frequency of females increases because of the ovule-fitness advantage usually associated with male sterility. When autosomal restorer alleles are present (autosomal control), the frequency of females tends to decline. The opposite directions of evolution favored by the cytoplasm and autosomes reflect the inherent conflict of interest between genomic subsets over the sex-allocation ratio. The evolutionary dynamics depend on an interaction between the phenotypic and genotypic frequencies and on the continual loss and reintroduction of genetic novelty over evolutionary time. A striking difference was observed between the potential genetic control of male sterility built into the simulation model, which reflects assumptions about the underlying physiological mechanisms of normal and aberrant pollen production, and the types of genetic control that would be inferred by performing classical genetic crossing experiments on a sample of the simulated population. This contrast between potential and inferred control is possibly an important general attribute of traits that are the resolution of a continual evolutionary conflict.

PERSPECTIVE: REPRESSION OF COMPETITION AND THE EVOLUTION OF COOPERATION

Abstract Repression of competition within groups joins kin selection as the second major force in the history of life shaping the evolution of cooperation. When opportunities for competition against neighbors are limited within groups, individuals can increase their own success only by enhancing the efficiency and productivity of their group. Thus, characters that repress competition within groups promote cooperation and enhance group success. Leigh first expressed this idea in the context of fair meiosis, in which each chromosome has an equal chance of transmission via gametes. Randomized success means that each part of the genome can increase its own success only by enhancing the total number of progeny and thus increasing the success of the group. Alexander used this insight about repression of competition in fair meiosis to develop his theories for the evolution of human sociality. Alexander argued that human social structures spread when they repress competition within groups and promote successful group-against-group competition. Buss introduced a new example with his suggestion that metazoan success depended on repression of competition between cellular lineages. Maynard Smith synthesized different lines of thought on repression of competition. In this paper, I develop simple mathematical models to illustrate the main processes by which repression of competition evolves. With the concepts made clear, I then explain the history of the idea. I finish by summarizing many new developments in this subject and the most promising lines for future study.

HIERARCHICAL SELECTION THEORY AND SEX RATIOS. II. ON APPLYING THE THEORY, AND A TEST WITH FIG WASPS

Predictions from the theory of sex ratios in subdivided populations are tested by studying fig wasps (Agaonidae). Observations strongly support the qualitative prediction that fig wasp sex ratios (males/total) decrease with increasing amounts of both inbreeding and competition among male relatives for access to mates (local mate competition). However, the observed sex ratio is consistently lower than predicted by previous quantitative models. Many assumptions underlying these models are unrealistic. Each unrealistic assumption is discussed as it applies to fig wasps, and where appropriate, new quantitative predictions are derived based on more realistic assumptions. New predictions are compared to the data in an a posteriori fashion and are found to be much closer to the observations than previous models from the literature, but further work will be required before a close match between theory and observation can be claimed.

Host-symbiont conflict over the mixing of symbiotic lineages.

Host and symbiont often conflict over patterns of symbiont transmission. Symbionts favour dispersal out of the host to avoid competition with close relatives. Migration leads to competition among different symbiotic lineages, with potentially virulent side-effects on the host. The hosts are favoured to restrict symbiont migration and reduce the virulent tendencies of the symbionts. Reduced mixing of symbionts would, in many cases, lower symbiont virulence and increase the mean fitness of the host population. But a host modifier allele that reduced symbiont mixing increases only when directly associated with reduced virulence. The association between modifiers and reduced virulence depends on the particular details of symbiont biology. The importance of this direct association between modifier and virulence was first noted by Hoekstra (1987) when studying the evolution of uniparental inheritance of cytoplasmic elements. I apply Hoekstra’s insight to a wide range of host–symbiont life histories, expanding the scope beyond cytoplasmic inheritance and genomic conflict. My comparison of differing symbiont life histories leads to a careful analysis of the conditions under which hosts are favoured to control mixing of their symbionts.

DIVERGENCE OF MEIOTIC DRIVE-SUPPRESSION SYSTEMS AS AN EXPLANATION FOR SEX-BIASED HYBRID STERILITY AND INVIABILITY

Two empirical generalizations about speciation remain unexplained: the tendency of the heterogametic sex to be sterile or inviable in F1 hybrids (Haldanes rule), and the tendency of the X chromosome to harbor the genetic elements that cause this sex bias in hybrid fitness. I suggest that divergence of meiotic drive systems on the sex chromosomes can explain these observations. The theory follows from two simple facts. First, sex chromosomes are particularly susceptible to the forces of meiotic drive. Second, divergence of meiotic drive systems can cause hybrid sterility and in viability. The main objection to the theory is that meiotic drive is apparently rare, whereas the observed pattern of hybrid fitness is widespread. I answer this objection by showing that divergence of meiotic drive systems can explain the two generalizations even if large departures from Mendelian segregation are rarely observed.

Evolution in a variable environment

We develop a general model for the effects of variation in reproductive success on gene-frequency change and phenotypic evolution. Our approach is based on distinguishing among individual, genotypic, and population-level reproductive success and on relating these three levels through correlations. For example, the variance of genotypic reproductive success can be expressed by individual-level variance and by the correlations among individuals. We use these correlations to show the simple relationship among earlier models of selection on the variance of reproductive success, of temporal variation in selection, of spatial variation in selection, and of variation in behavioral traits. Our approach also applies to diploid individuals by regarding diploidy as a way to induce correlations in reproductive success between pairs of alleles. We apply our method to patterns of developmental homeostasis, the evolution of iteroparity, and the effects of variability in resource acquisition under nonlinear gains. Finally, we discuss the uses and limitations of the geometric-mean principle, and we provide a precise description and formal methods of analysis for bet hedging and risk aversion

THE PRICE EQUATION, FISHER'S FUNDAMENTAL THEOREM, KIN SELECTION, AND CAUSAL ANALYSIS

A general framework is presented to unify diverse models of natural selection. This framework is based on the Price Equation, with two additional steps. First, characters are described by their multiple regression on a set of predictor variables. The most common predictors in genetics are alleles and their interactions, but any predictor may be used. The second step is to describe fitness by multiple regression on characters. Once again, characters may be chosen arbitrarily. This expanded Price Equation provides an exact description of total evolutionary change under all conditions, and for all systems of inheritance and selection. The model is first used for a new proof of Fishers fundamental theorem of natural selection. The relations are then made clear among Fishers theorem, Robertsons covariance theorem for quantitative genetics, the Lande‐Arnold model for the causal analysis of natural selection, and Hamiltons rule for kin selection. Each of these models is a partial analysis of total evolutionary change. The Price Equation extends each model to an exact, total analysis of evolutionary change for any system of inheritance and selection. This exact analysis is used to develop an expanded Hamiltons rule for total change. The expanded rule clarifies the distinction between two types of kin selection coefficients. The first measures components of selection caused by correlated phenotypes of social partners. The second measures components of heritability via transmission by direct and indirect components of fitness.

A Kin Selection Model for the Evolution of Virulence

The costs and benefits of parasite virulence are analysed in an evolutionarily stable strategy (ESS) model. Increased host mortality caused by disease (virulence) reduces a parasite’s fitness by damaging its food supply. The fitness costs of high virulence may be offset by the benefits of increased transmission or ability to withstand the host’s defences. It has been suggested that multiple infections lead to higher virulence because of competition among parasite strains within a host. A quantitative prediction is given for the ESS virulence rate as a function of the coefficient of relatedness among co-infecting strains. The prediction depends on the quantitative relation between the costs of virulence and the benefits of transmission or avoidance of host defences. The particular mechanisms by which parasites can increase their transmission or avoid host defences also have a key role in the evolution of virulence when there are multiple infections.

Fisher's fundamental theorem of natural selection

Fishers Fundamental Theorem of natural selection is one of the most widely cited theories in evolutionary biology. Yet it has been argued that the standard interpretation of the theorem is very different from what Fisher meant to say. What Fisher really meant can be illustrated by looking in a new way at a recent model for the evolution of clutch size. Why Fisher was misunderstood depends, in part, on the contrasting views of evolution promoted by Fisher and Wright.