Genome-wide association studies in Plasmodium species.

Genome-wide association studies (GWAS) look for correlations between traits of interest and genetic markers spread throughout the genome. A recent study in BMC Genetics has found that populations of the malaria parasite Plasmodium vivax should be amenable to GWAS searching for a genetic basis of parasite pathogenicity. Geographical substructure in populations may, however, prove a problem in interpreting the results.

Transient cross-reactive immune responses can orchestrate antigenic variation in malaria.

The malaria parasite Plasmodium falciparum has evolved to prolong its duration of infection by antigenic variation of a major immune target on the surface of the infected red blood cell. This immune evasion strategy depends on the sequential, rather than simultaneous, appearance of immunologically distinct variants. Although the molecular mechanisms by which a single organism switches between variants are known in part, it remains unclear how an entire population of parasites within the host can synchronize expression to avoid rapidly exhausting the variant repertoire. Here we show that short-lived, partially cross-reactive immune responses to parasite-infected erythrocyte surface antigens can produce a cascade of sequentially dominant antigenic variants, each of which is the most immunologically distinct from its preceding types. This model reconciles several previously unexplained and apparently conflicting epidemiological observations by demonstrating that individuals with stronger cross-reactive immune responses can, paradoxically, be more likely to sustain chronic infections. Antigenic variation has always been seen as an adaptation of the parasite to evade host defence: we show that the coordination necessary for the success of this strategy might be provided by the host.

Survival and weak chaos.

Survival analysis in biology and reliability theory in engineering concern the dynamical functioning of bio/electro/mechanical units. Here we incorporate effects of chaotic dynamics into the classical theory. Dynamical systems theory now distinguishes strong and weak chaos. Strong chaos generates Type II survivorship curves entirely as a result of the internal operation of the system, without any age-independent, external, random forces of mortality. Weak chaos exhibits (a) intermittency and (b) Type III survivorship, defined as a decreasing per capita mortality rate: engineering explicitly defines this pattern of decreasing hazard as 'infant mortality'. Weak chaos generates two phenomena from the normal functioning of the same system. First, infant mortality-sensu engineering-without any external explanatory factors, such as manufacturing defects, which is followed by increased average longevity of survivors. Second, sudden failure of units during their normal period of operation, before the onset of age-dependent mortality arising from senescence. The relevance of these phenomena encompasses, for example: no-fault-found failure of electronic devices; high rates of human early spontaneous miscarriage/abortion; runaway pacemakers; sudden cardiac death in young adults; bipolar disorder; and epilepsy.

The evolutionary ecology of molecular replicators.

By reasonable criteria, life on the Earth consists mainly of molecular replicators. These include viruses, transposons, transpovirons, coviruses and many more, with continuous new discoveries like Sputnik Virophage. Their study is inherently multidisciplinary, spanning microbiology, genetics, immunology and evolutionary theory, and the current view is that taking a unified approach has great power and promise. We support this with a new, unified, model of their evolutionary ecology, using contemporary evolutionary theory coupling the Price equation with game theory, studying the consequences of the molecular replicators' promiscuous use of each others' gene products for their natural history and evolutionary ecology. Even at this simple expository level, we can make a firm prediction of a new class of replicators exploiting viruses such as lentiviruses like SIVs, a family which includes HIV: these have been explicitly stated in the primary literature to be non-existent. Closely connected to this departure is the view that multicellular organism immunology is more about the management of chronic infections rather than the elimination of acute ones and new understandings emerging are changing our view of the kind of theatre we ourselves provide for the evolutionary play of molecular replicators. This study adds molecular replicators to bacteria in the emerging field of sociomicrobiology.

Imperfect vaccination: some epidemiological and evolutionary consequences.

An aim of some vaccination programmes is to reduce the prevalence of an infectious disease and ultimately to eradicate it. We show that eradication success depends on the type of vaccine as well as on the vaccination coverage. Vaccines that reduce the parasite within-host growth rate select for higher parasite virulence and this evolution may both increase the prevalence of the disease and prevent disease eradication. By contrast, vaccines that reduce the probability of infection select against virulence and may lead more easily to eradication. In some cases, epidemiological feedback on parasite evolution yields an evolutionary bistable situation where, for intermediate vaccination coverage, parasites can evolve towards either high or low virulence, depending on the initial conditions. These results have practical implications for the design and use of imperfect vaccines in public- and animal-health programmes.

Inbreeding and parasite sex ratios.

The breeding system of parasitic protozoa affects the evolution of drug resistance and virulence, and is relevant to disease diagnosis and the development of chemo- and immunotherapy. A major group of protozoan parasites, the phylum Apicomplexa, that includes the aetiological agents of malaria, toxoplasmosis and coccidiosis, all have dimorphic sexual stages. The sex ratio (proportion of males produced by parasites) is predicted to depend upon the inbreeding rate, and it has been suggested that sex-ratio data offer a relatively cheap and easy method for indirectly estimating inbreeding rates. Here, we exploit a new theoretical machinery to show that there are generally valid relationships between f, Wright's coefficient of inbreeding, and sex ratio, z(*), the generality being with respect to population structure. To focus the discussion, we concentrate on malaria and show that the previously derived result, f = 1 - 2z(*), does not depend on the artificial assumptions about population structure that were previously made. Not only does this justify the use of sex ratio as an indirect measure of f, but also we argue that it may actually be preferable to measure f by measuring sex ratios, rather than by measuring departures from Hardy-Weinberg genotypic proportions both in malaria and parasites more generally.

Fertility insurance and the sex ratios of malaria and related hemospororin blood parasites.

The sex ratio (z*; proportion of gametocytes that are male) of malaria and related hemospororin blood parasites has been predicted to be related to the inbreeding rate (f) by the simple equation z* = (1 - f)/2. Although there is some empirical support for this prediction, there are several cases where the sex ratio is less female biased or more variable than expected. Here, we present a theoretical model that may be able to explain some of these discrepancies. We show that if low gametocyte densities lead to a danger that female gametes may not encounter any male gametes, then natural selection favors a less female-biased sex ratio as a form of 'fertility insurance' to ensure that female gametes are mated. This model can be applied to a number of situations. In particular, (1) empirical data suggest that the number of gametocyes per blood meal can be low enough to favor fertility insurance in some Plasmodium infections in humans and (2) our model predicts facultative shifting toward less-biased sex ratios in response to immune pressure that reduces gametocyte or gamete survival or mobility, consistent with some recent experimental data from Plasmodium species of birds and mice.

Controlling for non-independence in comparative analysis of patterns across populations within species.

How do we quantify patterns (such as responses to local selection) sampled across multiple populations within a single species? Key to this question is the extent to which populations within species represent statistically independent data points in our analysis. Comparative analyses across species and higher taxa have long recognized the need to control for the non-independence of species data that arises through patterns of shared common ancestry among them (phylogenetic non-independence), as have quantitative genetic studies of individuals linked by a pedigree. Analyses across populations lacking pedigree information fall in the middle, and not only have to deal with shared common ancestry, but also the impact of exchange of migrants between populations (gene flow). As a result, phenotypes measured in one population are influenced by processes acting on others, and may not be a good guide to either the strength or direction of local selection. Although many studies examine patterns across populations within species, few consider such non-independence. Here, we discuss the sources of non-independence in comparative analysis, and show why the phylogeny-based approaches widely used in cross-species analyses are unlikely to be useful in analyses across populations within species. We outline the approaches (intraspecific contrasts, generalized least squares, generalized linear mixed models and autoregression) that have been used in this context, and explain their specific assumptions. We highlight the power of 'mixed models' in many contexts where problems of non-independence arise, and show that these allow incorporation of both shared common ancestry and gene flow. We suggest what can be done when ideal solutions are inaccessible, highlight the need for incorporation of a wider range of population models in intraspecific comparative methods and call for simulation studies of the error rates associated with alternative approaches.

The generation of influenza outbreaks by a network of host immune responses against a limited set of antigenic types.

It is commonly believed that influenza epidemics arise through the incremental accumulation of viral mutations, culminating in a novel antigenic type that is able to escape host immunity. Successive epidemic strains therefore become increasingly antigenically distant from a founding strain. Here, we present an alternative explanation where, because of functional constraints on the defining epitopes, the virus population is characterized by a limited set of antigenic types, all of which may be continuously generated by mutation from preexisting strains and other processes. Under these circumstances, influenza outbreaks arise as a consequence of host immune selection in a manner that is independent of the mode and tempo of viral mutation. By contrast with existing paradigms, antigenic distance between epidemic strains does not necessarily accumulate with time in our model, and it is the changing profile of host population immunity that creates the conditions for the emergence of the next influenza strain rather than the mutational capabilities of the virus.

Quantifying the roles of immigration and chance in shaping prokaryote community structure.

Naturally occurring populations of bacteria and archaea are vital to life on the earth and are of enormous practical significance in medicine, engineering and agriculture. However, the rules governing the formation of such communities are still poorly understood, and there is a need for a usable mathematical description of this process. Typically, microbial community structure is thought to be shaped mainly by deterministic factors such as competition and niche differentiation. Here we show, for a wide range of prokaryotic communities, that the relative abundance and frequency with which different taxa are observed in samples can be explained by a neutral community model (NCM). The NCM, which is a stochastic, birth-death immigration process, does not explicitly represent the deterministic factors and therefore cannot be a complete or literal description of community assembly. However, its success suggests that chance and immigration are important forces in shaping the patterns seen in prokaryotic communities.

The illusion of invariant quantities in life histories.

Life-history theory attempts to provide evolutionary explanations for variations in the ways in which animal species live their lives. Recent analyses have suggested that the dimensionless ratios of several key life-history parameters are the same for different species, even across distant taxa. However, we show here that previous analyses may have given a false picture and created an illusion of invariants, which do not necessarily exist; essentially, this is because life-history variables have been regressed against themselves. The following question arises from our analysis: How do we identify an invariant?

THE EVOLUTION OF COSTLY MATE PREFERENCES I. FISHER AND BIASED MUTATION.

Fisher's runaway process is the standard explanation of the evolution of exaggerated female preferences. But mathematical formulations of Fisher's process (haploid and additive diploid) show it cannot cause stable exaggeration if female preference carries a cost. At equilibrium female fitness must be maximized. Our analysis shows that evolutionary stable exaggeration of female preference can be achieved if mutation pressure on the male character is biased, that is, mutation has a directional effect. At this equilibrium female fitness is not maximized. We discuss the reasons and evidence for believing that mutation pressure is typically biased. Our analysis highlights the previously unacknowledged importance of biased mutation for sexual selection.

THE EVOLUTION OF COSTLY MATE PREFERENCES II. THE "HANDICAP" PRINCIPLE.

We use a general additive quantitative genetic model to study the evolution of costly female mate choice by the "handicap" principle. Two necessary conditions must be satisfied for costly preference to evolve. The conditions are (i) biased mutation pressure on viability and (ii) a direct relationship between the degree of expression of the male mating character and viability. These two conditions explain the success and failure of previous models of the "handicap" principle. Our model also applies to other sources of fitness variation like migration and host-parasite coevolution, which cause effects equivalent to biased mutation.

PHYLOGENIES WITHOUT FOSSILS.

Phylogenies that are reconstructed without fossil material often contain approximate dates for lineage splitting. For example, particular nodes on molecular phylogenies may be dated by known geographic events that caused lineages to split, thereby calibrating a molecular clock that is used to date other nodes. On the one hand, such phylogenies contain no information about lineages that have become extinct. On the other hand, they do provide a potentially useful testing ground for ideas about evolutionary processes. Here we first ask what such reconstructed phylogenies should be expected to look like under a birth-death process in which the birth and death parameters of lineages remain constant through time. We show that it is possible to estimate both the birth and death rates of lineages from the reconstructed phylogenies, even though they contain no explicit information about extinct lineages. We also show how such phylogenies can reveal mass extinctions and how their characteristic footprint can be distinguished from similar ones produced by density-dependent cladogenesis.