Evolutionary Origins of Southeast Asian Ovalocytosis

这项研究为东南亚和西太平洋疟疾的历史提供了新的见解。此外，它还将对一种等位基因的地理起源和传播进行详细分析，这种等位基因对人类健康有积极和消极的深刻影响(通过减轻疟疾的影响，同时也具有隐性致命性)。因此，这项研究使人们能够深入了解塑造东南亚地区当前人类健康模式的历史演变过程。此外，它还为高中、大学和研究生提供了在分子种群遗传学领域的重要培训机会。在许多受影响的人类种群中，疟疾是一种强大的自然选择因子。通过研究赋予疟疾抵抗力的等位基因的进化起源，我们可以深入了解导致疟疾的疟原虫寄生虫和人类宿主之间的共同进化关系。本研究探讨东南亚卵细胞增多症(SAO)的进化史。这一特征与对疟疾相关死亡率的强大抵抗力有关，但当个体的因果等位基因纯合时，在子宫中是致命的。因此，在受影响的人群中，SAO可能保持平衡的多态。这个项目的目标是通过对地理上不同的受影响个体的SAO和野生型等位基因进行重新测序来估计SAO起源的时间和地点。目前，我们对人类疟疾抗药性进化起源的绝大多数理解来自对撒哈拉以南非洲特征的研究。SAO的分布主要局限于东南亚和西太平洋地区--我们对该地区人类对疟疾的适应情况知之甚少。该项目测试SAO起源是否与迄今为止研究的其他(主要是非洲)抗疟疾等位基因是同时代的，并将确定这种适应等位基因进化的地理环境。

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.