School of Life Sciences, Arizona State University, Tempe, USA.
Heredity (Edinb). 2011 Oct;107(4):283-304. doi: 10.1038/hdy.2011.16. Epub 2011 Mar 23.
The high mortality and widespread impact of malaria have resulted in this disease being the strongest evolutionary selective force in recent human history, and genes that confer resistance to malaria provide some of the best-known case studies of strong positive selection in modern humans. I begin by reviewing JBS Haldane's initial contribution to the potential of malaria genetic resistance in humans. Further, I discuss the population genetics aspects of many of the variants, including globin, G6PD deficiency, Duffy, ovalocytosis, ABO and human leukocyte antigen variants. Many of the variants conferring resistance to malaria are 'loss-of-function' mutants and appear to be recent polymorphisms from the last 5000-10 000 years or less. I discuss estimation of selection coefficients from case-control data and make predictions about the change for S, C and G6PD-deficiency variants. In addition, I consider the predicted joint changes when the two β-globin alleles S and C are both variable in the same population and when there is a variation for α-thalassemia and S, two unlinked, but epistatic variants. As more becomes known about genes conferring genetic resistance to malaria in humans, population genetics approaches can contribute both to investigating past selection and predicting the consequences in future generations for these variants.
疟疾的高死亡率和广泛影响导致其成为人类近代史上最强的进化选择力量，而对疟疾具有抗性的基因则为现代人类中最强的正选择提供了一些最为知名的案例研究。我首先回顾了 JBS·霍尔丹（JBS Haldane）对人类疟疾遗传抗性的潜在作用的最初贡献。此外，我还讨论了许多变体的群体遗传学方面，包括珠蛋白、G6PD 缺乏症、Duffy、椭圆形红细胞增多症、ABO 和人类白细胞抗原变体。许多赋予疟疾抗性的变体是“功能丧失”突变体，似乎是最近的 5000-10000 年或更短时间内的多态性。我讨论了从病例对照数据估计选择系数的问题，并对 S、C 和 G6PD 缺乏症变体的变化进行了预测。此外，当两个β-珠蛋白等位基因 S 和 C 在同一人群中都是可变的，并且当存在α-地中海贫血和 S 的变体时，我还考虑了两个不相关但具有上位性的变体的联合变化。随着人们对赋予人类疟疾遗传抗性的基因的了解越来越多，群体遗传学方法不仅可以帮助研究过去的选择，还可以预测这些变体在未来几代人中的后果。
