Data from: Natural selection for the Duffy-null allele in the recently admixed people of Madagascar

While gene flow between distantly related populations is increasingly recognized as a potentially important source of adaptive genetic variation for humans, fully characterized examples are rare. In addition, the role that natural selection for resistance to vivax malaria may have played in the extreme distribution of the protective Duffy-null allele, which is nearly completely fixed in mainland sub-Saharan Africa and absent elsewhere, is controversial. We address both these issues by investigating the evolution of the Duffy-null allele in the Malagasy, a recently admixed population with major ancestry components from both East Asia and mainland sub-Saharan Africa. We used genome-wide genetic data and extensive computer simulations to show that the high frequency of the Duffy-null allele in Madagascar can only be explained in the absence of positive natural selection under extreme demographic scenarios involving high genetic drift. However, the observed genomic single nucleotide polymorphism diversity in the Malagasy is incompatible with such extreme demographic scenarios, indicating that positive selection for the Duffy-null allele best explains the high frequency of the allele in Madagascar. We estimate the selection coefficient to be 0.066. Because vivax malaria is endemic to Madagascar, this result supports the hypothesis that malaria resistance drove fixation of the Duffy-null allele in mainland sub-Saharan Africa.

尽管学界日益认识到，远缘种群间的基因流是人类适应性遗传变异的潜在重要来源，但得到完整解析的此类案例仍寥寥无几。此外，针对间日疟（vivax malaria）抗性的自然选择可能在保护性达菲阴性等位基因（Duffy-null allele）的极端分布中发挥了关键作用——该等位基因在撒哈拉以南非洲大陆几乎完全固定，却在其他地区完全缺失——这一假说仍存在争议。本研究通过探究马达加斯加人群中达菲阴性等位基因的演化历程，以解决上述两个问题。马达加斯加人群是近期形成的混血群体，其主要遗传血统组分分别源自东亚与撒哈拉以南非洲大陆。我们借助全基因组遗传数据与大规模计算机模拟，证实马达加斯加人群中达菲阴性等位基因的高频率，仅能在无正向自然选择且伴随极强遗传漂变的极端人口统计学情景下得到解释。然而，我们在马达加斯加人群中观测到的基因组单核苷酸多态性（single nucleotide polymorphism, SNP）多样性，与这类极端人口统计学情景并不兼容，这表明达菲阴性等位基因所受的正向选择，最能解释该等位基因在马达加斯加的高频率现象。我们估算得到该等位基因的选择系数为0.066。鉴于间日疟在马达加斯加呈地方性流行，这一结果支持了“疟疾抗性推动达菲阴性等位基因在撒哈拉以南非洲大陆发生固定”的假说。