Parasitism was recognized as a potent evolutionary force by Haldane as early as 1949 but was then largely ignored by evolutionary biologists until the mid-1970s. Interest has since been rekindled, and parasites have now been attributed major roles in areas of evolutionary biology as fundamental and diverse as social behaviour, sexual reproduction, ornamentation and speciation. These ideas have their roots in evolutionary theory, and parasitologists have as yet contributed little to their development and testing. Likewise, evolutionary biologists have been slow to assimilate the parasitological literature. This year's BSP Autumn Symposium was thus organized with the aim of promoting constructive interchange between the two disciplines.

(1) The evolutionary biology of molecular parasites by s. NEE and j. MAYNARD SMITH.

The British Society for Parasitology gratefully acknowledges financial support for this meeting from the following organisations:

A parasite can be considered to be the device of a nucleic acid which allows it to exploit the gene products of other nucleic acid–the host organisms. In this view, all parasites are ‘molecular parasites’. But it is interesting to restrict our attention to nucleic acids which do not encode organisms, as these live in a purely molecular world which lacks emergent features such as fangs and ovipositors. Viruses and transposons are molecular parasites in this sense. Most viral nucleic acids do code for some proteins, such as replicases and the protein shell in which they travel between their cellular oases. Some, however, do not even have a shell and code for nothing at all–these are the ‘viroids’ (Reisner & Gross, 1985), the smallest parasites in the world.

The object of this paper is to suggest that there may be an unexpected connexion between parasites and the evolution of sex, using for illustration an unfamiliar type of parasite, the selfish chromosome. The major intellectual challenge of sexuality is to an environment which is continually getting worse. The elegant solution given by the Red Queen theory (Levin, 1975; Hamilton, 1980; Bell, 1982; Bell & Maynard Smith, 1988) is that the relevant aspect of the environment is provided by antagonists—pathogens, predators and competitors—which, because they can respond adaptively so as to negate any improvement that has been made, provide a constant stimulus for continued evolution. Sexuality and recombination are favoured because some of the new combinations of genes which they create are resistant to the current population of antagonists. In other respects, sex and recombination are probably highly disadvantageous: outcrossed sex is expensive because it halves the rate of transmission of genes, while recombination breaks up successful combinations of genes. It is only in certain circumstances that the necessity for continual counter-adaptation will overcome these disadvantages: in particular, the damage (reduction in fitness) caused by an antagonist must be substantial, and the amount of damage must depend on a genetic interaction between the antagonistic species. These requirements are often satisfied by host—parasite systems, where both the ecological and genetic interactions between the antagonists may be very severe and highly specific (see reviews by Day, 1974 and Burdon, 1987). It is possible, therefore, that sex and recombination are maintained in natural populations largely through the dynamics of the coevolution of hosts and their parasites. This is certainly compatible with the major ecological patterns shown by sexual systems, with outcrossed sex being more common in the sea than in freshwater, more common at low than at high latitudes, and generally more common in stable, complex, climax environments where interactions between species are expected to be more frequent and intense (Bell, 1982). However, there is as yet no evidence which conclusively supports a direct causal link between the incidence of parasitism and the rate of recombination. In particular, it has never been demonstrated that a particular parasite has the effect of eliciting, directly or indirectly, a greater rate of genetic recombination in its host. We suggest that such a parasite exists; both the parasite and its effects are well known, but have never been interpreted in the context of the evolution of recombination through host—parasite coevolution. It is in many respects a rather unusual parasite. We shall argue that B-chromosomes represent highly evolved parasitic DNA, transmitted through the germ line and often eliciting greater rates of recombination in the host genome.

Evolutionary pressures exerted by parasites on the immune system, and vice versa, are surveyed from a speculative viewpoint. New information is presented about the possible channelling of suppression by MHC Class II genes in the mouse, where a novel pattern of dominant unresponsiveness mediated by H-2Ab is described. In addition, the hypothesis is advanced that phosphatidyl–inositol anchorage on the surface of parasites may represent a novel evasion mechanism, in which the spread of the immune response by epitope linkage is inhibited by host phospholipase.

The negative consequences of parasitic infection (virulence) were examined for two lizard malaria parasite—host associa tions: Plasmodium agamae and P. giganteum, parasites of the rainbow lizard, Agama agania, in Sierra Leone, West Africa; and P. mexicanum in the western fence lizard, Sceloporus occidentalis, in northern California. These malaria species vary greatly in their reproductive characteristics: P. agamae produces only 8 merozoites per schizont, P. giganteum yields over 100, and P. mexicanum an intermediate number. All three parasites appear to have had an ancient association with their host. In fence lizards, infection with malaria is associated with increased numbers of immature erythrocytes, decreased haemoglobin levels, decreased maximal oxygen consumption, and decreased running stamina. Not affected were numbers of erythrocytes, resting metabolic rate, and sprint running speed which is supported by anaerobic means in lizards. Infected male fence lizards had smaller testes, stored less fat in preparation for winter dormancy, were more often socially submissive and, unexpectedly, were more extravagantly coloured on the ventral surface (a sexually dimorphic trait) than non-infected males. Females also stored less fat and produced smaller clutches of eggs, a directly observed reduction in fitness. Infected fence lizards do not develop behavioural fevers. P. mexicanum appears to have broad thermal buffering abilities and thermal tolerance; the parasite's population growth was unaffected by experimental alterations in the lizard's body temperature. The data are less complete for A. agama, but infected lizards suffered similar haematological and physiological effects. Infected animals may be socially submissive because they appear to gather less insect prey, possibly a result of being forced into inferior territories. Infection does not reduce clutch size in rainbow lizards, but may lengthen the time between clutches. These results are compared with predictions emerging from several models of the evolution of parasite virulence. The lack of behavioural fevers in fence lizards may represent a physiological constraint by the lizards in evolving a thermal tolerance large enough to allow elimination of the parasite via fever. Such constraints may be important in determining the outcome of parasite—host coevolution. Some theory predicts low virulence in old parasite—host systems and higher virulence in parasites with greater reproductive output. However, in conflict with this argument, all three malarial species exhibited similar high costs to their hosts.

Defences against parasites are characterized by inducible, amplifiable responses, often with a memory component. Inducible defences with similar properties are common in a variety of other types of interactions, for example many aquatic invertebrates produce inducible structural defences against their predators and competitors. Most inducible defences have the following properties: (1) a threshold of activation; (2) an amplification of response with increasing stimulus; (3) a memory component. Specificity, amplification and memory are the basis for defining a defence as ‘immune’ (Klein, 1982), and these properties are present in both the vertebrate and invertebrate internal defence responses to pathogens. Invertebrates differ in the absence of immunoglobulins and therefore in reduced specificity. Although the reduced specificity of invertebrate internal defence systems is often viewed as proof of their ‘primitiveness’, the differences in defence systems of vertebrates and invertebrates may be more related to their respective selection regimes than to phylogeny. The syngeneic recognition system of vertebrates functions to recognize small departures from self, such as would arise from neoplasia. Are vertebrates under more intense selection from neoplasia, perhaps due to a greater incidence of hormonal imbalance or hypersensitivity reactions? The invertebrate internal defence systems are all less discriminating than the vertebrate, but there are marked differences in degree of discrimination depending on whether the group is colonial or not. Even the phyla of colonial animals with quite simple body plans, the sponges and cnidarians, have a more discriminating recognition system than the phyla of solitary animals with more complex body plans, such as the molluscs and arthropods. The primary effectors of all invertebrate responses to parasites are encapsulation and phagocytosis, although in some phyla there are specific antibacterial proteins that can also be induced. A primary effector of the vertebrate immune system is also based on phagocytosis, but is mediated largely by immunoglobulins. Although memory is a widespread property of inducible defence systems, the mechanisms, underlying memory components are unknown except in the vertebrate immune response. The function and adaptiveness of many of these accelerated or amplified second-set responses remain unclear, although it is tempting to conclude that a memory component is a beneficial adaptation to multiple, intermittent stimuli. From this review I conclude that the conditions that favour the evolution of inducible defences include: (1) an intermittent, unpredictable selective regime; (2) selection for a ‘camouflaged’ defence, to slow parasite counter-adaptation; (3) reliable cues and (4) high costs of defence.

Eavesdrop morning coffee at any major centre of evolutionary theory today, and you will find ‘parasite’ to be one of the commonest words in the language. Parasites are touted as prime movers in the evolution of sex, promising the final solution to that problem of problems, the puzzle that led G. C. Williams to proclaim in 1975 ‘a kind of crisis’ at hand in evolutionary biology (Hamilton, 1980; Tooby, 1982; Seger & Hamilton, 1988). Parasites seem to offer a plausible justification for the otherwise futile effort females put into choosing among posturing males (Hamilton & Zuk, 1982; but see Read, 1990). Frequency-dependent selection exerted by parasites is, according to one admittedly minority view, largely responsible for the high levels of diversity found in gene pools (Clarke, 1979). One might even extrapolate to a time when the entire metazoan body could come to be seen as a gigantic adaptation against microscopic pathogens.

The study of genetic exchange systems and the use of genetic analysis has been relatively limited in parasites leading to considerable gaps in our basic knowledge. This lack of knowledge makes it difficult to draw firm conclusions as to how these systems evolved. An additional problem is also raised by the difficulties in defining evolutionary distances particularly with the unicellular protozoa, using classical ultrastructural and cytological criteria. While these difficulties have by no means been overcome, the use of rapid sequencing techniques applied to the ribosomal genes has allowed measurement of evolutionary distances, and considerable advances in our understanding of the genetic exchange systems in a few parasitic protozoa have recently been made. The conclusions from these recent sets of analyses are reviewed and then examined together in order to discuss the evolution of genetic exchange systems in parasitic protozoa. The evolutionary distances defined by ribosome sequence analysis show that parasites are an extremely divergent group, with distances which, in some cases, are orders of magnitude greater than the distances between mammals and fish; furthermore these studies suggest that the parasitic protozoa or their free-living ancestors are extremely ancient. These findings support the view that parasitism has occurred independently many times and that the parasitic life-style has been adopted by evolutionarily distinct groups. The recent observation of a non-obligatory genetic exchange system in the diploid but evolutionarily ancient kinetoplastid Trypanosoma brucei suggests that diploidy and meiosis are extremely old. The observation, in parasitic protozoa and helminths, that selfing or non-obligatory mating is a common feature suggests that these processes may be strategies to overcome the cost of meiosis. In this context, the question of what selective forces maintain genetic exchange is discussed.

In this paper we wish to develop three themes, each having to do with evolutionary aspects of associations between hosts and parasites (with parasite defined broadly, to include viruses, bacteria and protozoans, along with the more conventionally defined helminth and arthropod parasites). The three themes are: the evolution of virulence; the population dynamics and population genetics of host–parasite associations; and invasions by, or ‘emergence’ of, new parasites.

Why do parasites kill their hosts? During this past decade, research in three different areas; evolutionary ecology, medical microbiology, and population genetics has provided theory and data that address this and related questions of selection and the evolution and maintenance of parasite virulence. A general theory of parasite–host coevolution and the conditions for selection to favour parasite virulence has been put forth. Considerable advances have been made in elucidating the mechanisms of pathogenicity and inheritance of virulence in bacteria. The population genetic structure and the relation ship between pathogenic and non-pathogenic forms has been determined for a number of species of bacteria. We critically review these developments and their implications for questions of selection and the evolution and maintenance of virulence in bacteria. We postulate how selection may operate on specific types of bacterial virulence and present a general protocol to experimentally test hypotheses concerning selection and the evolution of virulence in bacteria.