Infectious disease has long been recognised as a potent selective force. Malaria provides us with our best examples of recent human evolution, through the changes it has wrought within human globin genes. Mutations responsible for genetic blood disorders, such as the thalassaemias and sickle cell anaemia, reach high frequencies in malarious regions due to the protection they offer against death from malaria. However, evidence is growing that malaria protective haemoglobin mutations interact with one another in surprising ways. Alpha and beta thalassaemia can alleviate one another's blood disorders when co-inherited; alpha thalassaemia seems to cancel out the malaria protection offered by sickle cell trait. In the first half of this thesis I explore the population genetic consequences of these intracellular interactions, and show that they help account for two observations: (i) alpha thalassaemia frequencies do not exceed 50% in sub-Saharan Africa, and (ii) the relative rarity of the sickle cell gene in the Mediterranean. Another human genomic region where intriguing patterns emerge is the major histocompatibility complex. This region contains the Human Leukocyte Antigen (HLA) genes that encode the molecules responsible for displaying antigenic fragments to the adaptive arm of the immune system; HLA genes display a high degree of haplotypic structuring. In the second half of this thesis I explore the interplay between antigenic variation in the pathogen and recognition heterogeneity in the host. I demonstrate that host heterogeneity can significantly affect the type of strain structuring that is possible in the pathogen, and show that strain structuring in the pathogen can generate linkage disequilibrium between recognition loci in the host. Finally, I demonstrate that feedbacks between host and pathogen can generate a new type of co-evolutionary cycling, in which different strain structures periodically emerge in the pathogen, precipitating changes in the host population.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:558717 |
| Date | January 2012 |
| Creators | Penman, Bridget Sarah |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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