Evolutionary Origins of Southeast Asian Ovalocytosis

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This research provides novel insights into the history of malaria in Southeast Asia and the Western Pacific. Moreover, it will supply a detailed analysis of the geographic origins and spread of an allele that profoundly affects human health in both positive and negative ways (by mitigating the effects of malaria, while also being recessively lethal). As a result, this research enables insight into the historical evolutionary processes that shape current patterns of human health in the Southeast Asian region. In addition, it presents significant training opportunities for students at the high school, college, and graduate level in the field of molecular population genetics.Malaria acts as a powerful agent of natural selection in many affected human populations. By studying the evolutionary origins of alleles that confer resistance to malarial disease we can gain insights into the co-evolutionary relationship between malaria-causing Plasmodium parasites and human hosts. This study examines the evolutionary history of Southeast Asian Ovalocytosis (SAO). This trait is associated with strong resistance to malaria-related mortality but is lethal in utero when an individual is homozygous for the causal allele. As a consequence, SAO is likely maintained as a balanced polymorphism in affected populations. The goal of this project is to estimate the time and place where SAO originated by re-sequencing SAO and wildtype alleles from a geographically diverse panel of affected individuals. At present, the vast majority of our understanding of the evolutionary origins of human malaria-resistance comes from studies of sub-Saharan African traits. SAO has a distribution that is largely restricted to Southeast Asia and the Western Pacific -- an area from which we know comparatively little regarding human adaptation to malaria. This project tests whether SAO origins are contemporaneous with other (primarily African) malaria resistance alleles studied to date, and also will determine the geographic setting in which this adaptive allele evolved.