Despite over a century of research, malaria parasites (Plasmodium) still remain a major cause of mortality and morbidity worldwide. In recent years, the application of theoretical principles from ecology and evolutionary biology to the study of these parasites has started to provide insight into variety of fundamental subjects from the evolution of virulence to the facultative strategies (i.e. phenotypic plasticity) that parasites use to maximize their transmission. It is now becoming increasingly clear that to understand and predict population level patterns of virulence and transmission, the processes that occur at the between-host level must be studied in light of the interactions that happen within hosts (between parasites and between parasites and hosts). In this thesis I combine concepts from evolutionary biology and ecology with tools from molecular and cellular biology and evolutionary genetics, which allow me to study rodent malaria parasites at both evolutionary and ecological timescales. The work I present in this thesis has the following four components: 1. Phylogenetics (chapter 2): I applied recently developed phylogenetic methods to a large DNA sequence dataset that I generated, to provide a better understanding of the phylogeny of rodent malaria parasites and investigate how selection has shaped their genomes. I show that all rodent malaria subspecies can be considered species, provide the first time line for the evolution of this group of parasites and demonstrate that most loci are under purifying selection. 2. Hybridization and reproductive isolation (chapter 3): I show that hybridization between two rodent malaria parasites (P. berghei and P. yoelii) can occur, but only occurs at high levels when one of two proteins (P230 or P48/45) is absent from the surface of female gametes, which indicates that these proteins are involved in gamete recognition. I find that P230, P48/45 and P47 (a possible interaction partner) are evolving under positive selection, a feature often observed in gamete recognition proteins of other taxa. Finally, I show that the fertilization success of P. berghei is reduced in the presence of P. yoelii, but not vice-versa, which indicates asymmetric reproductive interference. 3. Sex allocation (chapter 4): I carry the first test of sex allocation’s assumption that immunity impacts on the fertility of Plasmodium male gametocytes/gametes more than on the fertility of females. I show that while the fertility of both males and females is equally affected, males are affected during gametogenesis and females are mostly affected through gamete dysfunction (i.e. gametes can mate but zygotes fail to develop), which is in agreement with the assumptions of theory. In collaboration, I incorporate these effects into sex allocation theory and predict that malaria parasites can minimize the effects of factors that kill gametocytes/gametes by adjusting their sex ratios. On the other hand sex ratio adjustment cannot compensate for gamete dysfunction or zygote death. These results have applied implications for transmission-blocking vaccines. 4. Infection dynamics of mixed-species infections (chapter 5): I develop a series of experiments to test how a focal parasite species (P. yoelii) is affected by competition with heterospecifics (P. chabaudi) and how the interaction between the two species is mediated by immunity and resource availability. I show that P. chabaudi can boost P. yoelii above its single species level (i.e. facilitation) and that this is mediated by resource availability. On the other hand, P. yoelii’s performance can also be hindered in mice that were exposed to a P. chabaudi infection. My results also reveal that host mortality is exacerbated in mixed-species infections of naïve mice, which may be due to an inability of the host to achieve the right balance between the production and the destruction of red blood cells, when dealing with a mixed-species infection. The work I present here tackles fundamental questions concerning the transmission biology and the within-host interactions of malaria parasites The results presented demonstrate the importance of interactions between hosts and parasites and between different parasite species (at the molecular and the whole organism levels) for determining the outcome of transmission, virulence and within-host parasite performance.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:575907 |
| Date | January 2012 |
| Creators | Ramiro, Ricardo Filipe Serrote |
| Contributors | Ricardo Filipe, Serrote Ramiro; Reece, Sarah; Obbard, Darren; West, Stuart |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/7542 |
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