Genomic Analysis of Plasmodium vivax in Southern Ethiopia Reveals Selective Pressures in Multiple Parasite Mechanisms

Genomic Analysis of Plasmodium vivax in Southern Ethiopia Reveals Selective Pressures in Multiple Parasite Mechanisms
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DOI:
10.1093/infdis/jiz016
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发表时间:
2019-12-01
影响因子:
6.4
通讯作者:
Price, Ric N.
Price, Ric N.
中科院分区:
医学2区
文献类型:
--
作者:
Auburn, Sarah;Getachew, Sisay;Price, Ric N.

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非洲之角拥有非洲大陆最大的间日疟原虫宿主。由于人类Duffy阴性特征的高度流行,撒哈拉以南非洲的大部分地区仍然相对没有间日疟原虫,但能够入侵Duffy阴性网织红细胞的菌株的出现构成了重大的公共卫生威胁。我们对该地区的间日疟原虫进行了首次群体基因组调查,将24个埃塞俄比亚分离株的基因组与东南亚的数据进行了比较,以确定重要的地方适应。在埃塞俄比亚,Duffy结合蛋白扩增的流行率为79%,可能反映了对Duffy阴性的适应。也有证据表明,在氯喹抗性转运蛋白上游的一个区域进行了选择,该转运蛋白是一种假定的氯喹抗性决定因素。在参与免疫逃避和基因表达调控的基因中观察到了强烈的选择信号,突显了需要多方面的干预方法来对抗该地区的间日疟原虫。
The Horn of Africa harbors the largest reservoir of Plasmodium vivax in the continent. Most of sub-Saharan Africa has remained relatively vivax-free due to a high prevalence of the human Duffy-negative trait, but the emergence of strains able to invade Duffy-negative reticulocytes poses a major public health threat. We undertook the first population genomic investigation of P. vivax from the region, comparing the genomes of 24 Ethiopian isolates against data from Southeast Asia to identify important local adaptions. The prevalence of the Duffy binding protein amplification in Ethiopia was 79%, potentially reflecting adaptation to Duffy negativity. There was also evidence of selection in a region upstream of the chloroquine resistance transporter, a putative chloroquine-resistance determinant. Strong signals of selection were observed in genes involved in immune evasion and regulation of gene expression, highlighting the need for a multifaceted intervention approach to combat P. vivax in the region.