Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum

Widespread use of antimalarial agents can profoundly influence the evolution of the human malaria parasite Plasmodium falciparum. Recent selective sweeps for drug-resistant genotypes may have restricted the genetic diversity of this parasite, resembling effects attributed in current debates to a historic population bottleneck. Chloroquine-resistant (CQR) parasites were initially reported about 45 years ago from two foci in southeast Asia and South America, but the number of CQR founder mutations and the impact of chlorquine on parasite genomes worldwide have been difficult to evaluate. Using 342 highly polymorphic microsatellite markers from a genetic map, here we show that the level of genetic diversity varies substantially among different regions of the parasite genome, revealing extensive linkage disequilibrium surrounding the key CQR gene pfcrt and at least four CQR founder events. This disequilibrium and its decay rate in the pfcrt-flanking region are consistent with strong directional selective sweeps occurring over only approximately 20-80 sexual generations, especially a single resistant pfcrt haplotype spreading to very high frequencies throughout most of Asia and Africa. The presence of linkage disequilibrium provides a basis for mapping genes under drug selection in P. falciparum.     

Field parameterization and experimental test of the neutral theory of biodiversity

Ecologists would like to explain general patterns observed across multi-species communities, such as species-area and abundance-frequency relationships, in terms of the fundamental processes of birth, death and migration underlying the dynamics of all constituent species. The unified neutral theory of biodiversity and related theories based on these fundamental population processes have successfully recreated general species-abundance patterns without accounting for either the variation among species and individuals or resource-releasing processes such as predation and disturbance, long emphasized in ecological theory. If ecological communities can be described adequately without estimating variation in species and their interactions, our understanding of ecological community organization and the predicted consequences of reduced biodiversity and environmental change would shift markedly. Here, I introduce a strong method to test the neutral theory that combines field parameterization of the underlying population dynamics with a field experiment, and apply it to a rocky intertidal community. Although the observed abundance-frequency distribution of the system follows that predicted by the neutral theory, the neutral theory predicts poorly the field experimental results, indicating an essential role for variation in species interactions.     

Local interactions predict large-scale pattern in empirically derived cellular automata.

An important unanswered question in ecology is whether processes such as species interactions that occur at a local scale can generate large-scale patterns seen in nature. Because of the complexity of natural ecosystems, developing an adequate theoretical framework to scale up local processes has been challenging. Models of complex systems can produce a wide array of outcomes; therefore, model parameter values must be constrained by empirical information to usefully narrow the range of predicted behaviour. Under some conditions, spatially explicit models of locally interacting objects (for example, cells, sand grains, car drivers, or organisms), variously termed cellular automata or interacting particle models, can self-organize to develop complex spatial and temporal patterning at larger scales in the absence of any externally imposed pattern. When these models are based on transition probabilities of moving between ecological states at a local level, relatively complex versions of these models can be linked readily to empirical information on ecosystem dynamics. Here, I show that an empirically derived cellular automaton model of a rocky intertidal mussel bed based on local interactions correctly predicts large-scale spatial patterns observed in nature.     

Sheep retrovirus structural protein induces lung tumours

Jaagsiekte sheep retrovirus (JSRV) causes a contagious lung cancer in sheep and goats, with significant animal health and economic consequences. The host range of JSRV is in part limited by species-specific differences in the virus entry receptor, hyaluronidase 2 (Hyal2), which is not functional as a receptor in mice but is functional in humans. Sheep are immunotolerant of JSRV because of the expression of closely related endogenous retroviruses, which are not present in humans and most other species, and this may facilitate oncogenesis. Here we show that expression of the JSRV envelope (Env) protein alone in lungs of mice, by using a replication-incompetent adeno-associated virus vector, results in tumours with a bronchiolo-alveolar localization like those seen in sheep. Whereas lethal disease was observed in immunodeficient mice, tumour development was almost entirely blocked in immunocompetent mice. Our results provide a rare example of an oncogenic viral structural protein, show that interaction of the viral Env protein with the virus entry receptor Hyal2 is not required for tumorigenesis, and indicate that immune recognition of Env can protect against JSRV tumorigenesis.