Trade-offs and the evolution of virulence of microparasites: do details matter?

Models of the within-host dynamics of parasites have been used to consider the evolution of microparasites causing acute infections in vertebrate hosts. In this paper, we use these models to examine how the level of virulence to which a parasite evolves, depends on factors such as the relationship between parasite density and its rate of transmission from infected hosts, and the mechanism of parasite-induced pathogenesis. We show that changes in the terms describing transmissibility and pathogenesis may lead to dramatic differences in the level of virulence to which a parasite evolves. This suggests that no single factor is likely to be responsible for the differences in virulence of different parasites, and that understanding of the evolution of virulence of parasites will require a detailed quantitative understanding of the interaction between the parasite and its host.     

How can immunopathology shape the evolution of parasite virulence?

Immunopathology (immune-mediated pathology) is a ubiquitous cause of disease during infection, but how will parasite exploitation strategies evolve in its presence? Immunopathology can act to increase parasite fitness if it increases transmission rate, but can equally act to decrease parasite fitness if it increases host mortality. The focus here is on understanding how immunopathology, mediated through different immune mechanisms, can influence parasite fitness and how experimental manipulations of the immune system can be carried out to examine this. A better understanding of how parasite fitness scales with, or responds to, immunopathology is crucial to understanding the nature of selection acting on parasite virulence traits and will allow more informed predictions to be made regarding the trajectory of parasite virulence evolution.     

What is mtDNA good for in the study of primate evolution?

Recombinant DNA methods have made accessible the nuclear and organelle genomes of a vast array of plant and animal species.^1–3 Although evolutionary biologists and anthropologists have begun to exploit the full range of these methods, a disproportionate share of this research has centered on the mitochondrial genome (mtDNA). Because of its small size, conserved organization, mode of inheritance, and combination of rapidly and slowly evolving regions, mtDNA (Fig. 1) has appeared in many ways to be the ideal molecule for evolutionary studies of primates.^4,5 However, recent research on higher primates raises serious concerns about the utility of this molecule for evolutionary analysis in the absence of parallel data from the nuclear genome.^6–8 These studies suggest that we need to rethink our research strategies and define more clearly what mtDNA can be used for in the study of primate evolution.     

Could the human papillomavirus vaccines drive virulence evolution?

The human papillomavirus (HPV) vaccines hold great promise for preventing several cancers caused by HPV infections. Yet little attention has been given to whether HPV could respond evolutionarily to the new selection pressures imposed on it by the novel immunity response created by the vaccine. Here, we present and theoretically validate a mechanism by which the vaccine alters the transmission–recovery trade-off that constrains HPV''s virulence such that higher oncogene expression is favoured. With a high oncogene expression strategy, the virus is able to increase its viral load and infected cell population before clearance by the vaccine, thus improving its chances of transmission. This new rapid cell-proliferation strategy is able to circulate between hosts with medium to high turnover rates of sexual partners. We also discuss the importance of better quantifying the duration of challenge infections and the degree to which a vaccinated host can shed virus. The generality of the models presented here suggests a wider applicability of this mechanism, and thus highlights the need to investigate viral oncogenicity from an evolutionary perspective.     

In silico prediction of the structure of membrane proteins: is it feasible?

In the 'omic' era, hundreds of genomes are available for protein sequence analysis, and some 30 per cent of all sequences are of membrane proteins. Unlike globular proteins, a 3D model for membrane proteins can hardly be computed starting from the sequence. Why is this so? What can we really compute and with what reliability? These and other matters are outlined.     

The evolution and maintenance of virulence in Staphylococcus aureus: a role for host-to-host transmission?

Despite progress in our understanding of infectious disease biology and prevention, the conditions that select for the establishment and maintenance of microbial virulence remain enigmatic. To address this aspect of pathogen biology, we focus on two members of the Staphylococcus genus - Staphylococcus aureus and Staphylococcus epidermidis - and consider why S. aureus has evolved to become more virulent than S. epidermidis. Several hypotheses to explain this phenomenon are discussed and a mathematical model is used to argue that a complex transmission pathway is the key factor in explaining the evolution and maintenance of virulence in S. aureus. In the case of S. epidermidis, where skin contact affords easier transmission between hosts, high levels of virulence do not offer an advantage to this pathogen.     

Three conditions for the evolution of eusociality: Are they sufficient?

Summary I hypothesize that three conditions, (1) food-shelter coincidence, (2) strong selection for defense, and (3) ability to defend, are sufficient, although not necessary, for the evolution of eusociality in group-living animals. Reasons for this association between ecology and eusociality include extremely high value of the habitat, possibilities for habitat inheritance, high relatedness in claustral situations, self-sufficiency of juveniles, greater ability of workers to reproduce, and trade-offs between defensive ability and dispersal.     

A model for the evolution of crèching behaviour in gulls

A crèche is an aggregation of chicks outside nesting territories, within chicks continue to be fed only by their own parents. Several adaptive functions of crèching have been proposed, the most frequent being a reduction in predator pressure. Using an evolutionary stable strategy approach based on the computation of individuals' fecundity, we examined which regime of aerial and terrestrial predation is likely to favour the evolution and stability of the crèching strategy (CS) in gulls. Our results confirm the hypothesis that habitat instability associated with high levels of terrestrial predation favours the evolution and maintenance of crèching behaviour. Moreover, our results suggest that a low aggressiveness against predators may be a pre-adaptation to a CS. In contrast, the high synchronisation often observed in crèching species does not favour the evolution of a crèching behaviour and is thus probably under selection pressures different from those modelled here.     

The quest for an AIDS vaccine: is the CD8+ T-cell approach feasible?

The rationale for developing anti-HIV vaccines that stimulate cytotoxic T-lymphocyte responses is given. We argue that such vaccines will work, provided that attention is paid to the development of memory T-cell responses that are strong and preferably activated. Furthermore, the vaccine should match the prevailing virus clade as closely as possible. Vaccines will have to stimulate a wide range of responses, but it is not clear how this can be achieved.     

Human evolution and the brain representation of semantic knowledge: is there a role for sex differences?

A sexual asymmetry has been recently found on semantic memory tasks: after brain damage, a disproportionate deficit for information about biological categories has been reported more frequently for male patients. A review of cases shows that the fine-grained pattern is more complicated in that there is a strong interaction with sex: Disproportionate plant-knowledge deficits are restricted to males, whereas disproportionate animal-knowledge deficits are rare and show no sex bias. These clinical data are consistent with semantic-knowledge data from normal subjects indicating a task-invariant female advantage with plant categories. In this study, we seek an explanation for this sex-by-semantic category interaction and discuss the possible roles of a greater female experience with plant items, both ontogenetically and over evolutionary time.     

Perioperative management of pheochromocytoma/paraganglioma: is there a state of the art?

Pheochromocytoma and paraganglioma are rare tumors of sympathetic or parasympathetic origin, presenting with a highly variable clinical picture. Rarity, as well as biological, clinical, and genetic heterogeneity are barriers to initiate prospective studies that help to establish clinical guidelines. The best management of these patients relies on the experience of a multidisciplinary team. The ultimate outcome can benefit from adequate pre-surgical evaluation and treatment as well as an accurate post-surgical follow-up. Long-term follow-up is mandatory in all patients, but is particularly important in specific familial cases such as those with an SDHB mutation where the risks of recurrence are higher. The surgical approach varies depending on tumor size, location, and surgeon's personal attitude and experience. In this paper, we summarize recommendations, based mostly on authors' and other experts' personal experiences, for the best possible management of patients prior, during and after surgery, as well as when pheochromocytoma is diagnosed during pregnancy.     

A model for the coevolution of resistance and virulence in coupled host—parasitoid interactions

A coevolutionary model is developed of the interaction between a host and an internal parasitoid, where the outcome of parasitism depends upon the extent to which individual hosts invest in resistance mechanisms and individual parasitoids in countermeasures (virulence). The host and parasitoid are assumed to have coupled population dynamics (of Nicholson–Bailey form) and to be composed of a series of asexual clones with different levels of resistance and virulence. Investment in resistance and virulence mechanisms is assumed to be costly. The model has two main outcomes. First, if resistance is relatively costly compared to virulence, the host may be selected not to invest in resistance mechanisms despite parasitoid investment in virulence, in effect trading off the risks of parasitism against the savings in costs. A number of cases which appear to correspond to this result have been reported. Second, for most other feasible parameter values, an arms race occurs between host and parasitoid, until effective resistance becomes so costly that the host abandons defence. This abandonment is followed by a reduction in parasitoid virulence and the cycle begins again. These cycles may explain reports of persistent additive genetic variation in resistance and virulence, and may also contribute towards population dynamic stability.     

The evolution of the neocortex in mammals: how is phenotypic diversity generated?

Evolution of the mammalian neocortex is difficult to examine directly. For this reason, comparative studies and developmental studies are the best way of gaining insight into the evolutionary process. Comparative studies indicate that neocortical evolution is constrained, and that the types of systems-level modifications made to the neocortex are limited. Developmental studies of gene expression suggest that genetic contingencies set up aspects of cortical organization and connectivity, and that the complex spatial and temporal interactions of genes constrain development and evolution. Although genes obviously contribute to phenotypic variability, variability can also be achieved through alterations in the sensory receptor arrays, or changes in sensory driven activity. The intracellular mechanisms that enable phenotypic variability might evolve, but often the phenotypic characteristic in question is context-dependent.     

The growth/predation risk trade-off: so what is the mechanism?

Among damselflies in natural lakes, Ischnura species grow faster than coexisting Enallagma species, but Enallagma species have higher survival under predation than Ischnura species. This growth/predation risk trade-off apparently allows these taxa to coexist in ponds and lakes across the Holarctic. However, laboratory studies presented here show that the mechanism assumed by most theoretical and empirical studies to mediate this trade-off, namely activity simultaneously modulating foraging returns and predation risk, does not operate in this system. Ischnura verticalis larvae were more active than larvae of Enallagma species in a short-term behavioral experiment, which explains why Ischnura experiences greater mortality from predation. However, this greater activity did not translate into higher feeding rates. Ischnura verticalis and Enallagma species ate comparable amounts of food in both the short-term behavioral experiment and a longer feeding and digestion experiment. In spite of no difference in the amount of food ingested or assimilated, I. verticalis larvae grew faster than Enallagma larvae because they were better able to physiologically convert assimilated food into their own biomass in the presence of mortality threats. From these studies we understand the phenotypic mechanisms determining the antagonistic patterns of relative growth and survival between these two genera, but why these patterns exist remains unclear.     

Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer?

Acute myeloid leukaemia (AML) is an uncontrolled clonal proliferation of abnormal myeloid progenitor cells in the bone marrow and blood. Advances in cancer genomics have revealed the spectrum of somatic mutations that give rise to human AML and drawn our attention to its molecular evolution and clonal architecture. It is now evident that most AML genomes harbour small numbers of mutations, which are acquired in a stepwise manner. This characteristic, combined with our ability to identify mutations in individual leukaemic cells and our detailed understanding of normal human and murine haematopoiesis, makes AML an excellent model for understanding the principles of cancer evolution. Furthermore, a better understanding of how AML evolves can help us devise strategies to improve the therapy and prognosis of AML patients. Here, we draw from recent advances in genomics, clinical studies and experimental models to describe the current knowledge of the clonal evolution of AML and its implications for the biology and treatment of leukaemias and other cancers.KEY WORDS: Acute myeloid leukaemia, Cancer, Clonal evolution, In vivo models of leukaemia, Mutation