Consistent signatures of selection from genomic analysis of pairs of temporal and spatial Plasmodium falciparum populations from The Gambia.

Consistent signatures of selection from genomic analysis of pairs of temporal and spatial Plasmodium falciparum populations from The Gambia.
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从冈比亚的颞和空间疟原虫对的基因组分析中选择的一致特征。

DOI:
10.1038/s41598-018-28017-5
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发表时间:
2018-06-26
期刊:
影响因子:
4.6
通讯作者:
D'Alessandro U
D'Alessandro U
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Amambua-Ngwa A;Jeffries D;Amato R;Worwui A;Karim M;Ceesay S;Nyang H;Nwakanma D;Okebe J;Kwiatkowski D;Conway DJ;D'Alessandro U

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对2008年和2014年在冈比亚收集的247株恶性疟原虫分离株的基因组序列进行了分析,以确定可能与这一时期抗疟干预措施规模扩大有关的变化。总的来说,基因组中有15个区域具有正选择的特征。其中5个是围绕已知的耐药性和抗原位点进行的扫描。在抗原位点的签名,如凝血酶相关的粘附蛋白(Pftrap)是最常见的冈比亚东部,寄生虫的患病率和传播仍然很高。有一个强大的时间分化,在一个非同义SNP的半胱氨酸蛋白酶(Pfnfs)参与铁-硫复合物的生物成因。在7年期间,在密码子65(Pfnfs-Q65 K)赖氨酸变异的频率增加了22%(10%至32%)在大班珠尔地区。2014年至2015年期间,冈比亚东部这种变异的频率增加了6%(20%至26%)。本芴醇的IC 50在Pfnfs-65 K分离株中显著更高。这可能是本芴醇对Pfnfs或连锁基因座进行定向选择的第一个证据。鉴于疟疾传播下降,随之而来的人口免疫力丧失,以及持续的药物压力,重要的是要监测冈比亚恶性疟原虫人口的进一步适应迹象。
Genome sequences of 247 Plasmodium falciparum isolates collected in The Gambia in 2008 and 2014 were analysed to identify changes possibly related to the scale-up of antimalarial interventions that occurred during this period. Overall, there were 15 regions across the genomes with signatures of positive selection. Five of these were sweeps around known drug resistance and antigenic loci. Signatures at antigenic loci such as thrombospodin related adhesive protein (Pftrap) were most frequent in eastern Gambia, where parasite prevalence and transmission remain high. There was a strong temporal differentiation at a non-synonymous SNP in a cysteine desulfarase (Pfnfs) involved in iron-sulphur complex biogenesis. During the 7-year period, the frequency of the lysine variant at codon 65 (Pfnfs-Q65K) increased by 22% (10% to 32%) in the Greater Banjul area. Between 2014 and 2015, the frequency of this variant increased by 6% (20% to 26%) in eastern Gambia. IC50 for lumefantrine was significantly higher in Pfnfs-65K isolates. This is probably the first evidence of directional selection on Pfnfs or linked loci by lumefantrine. Given the declining malaria transmission, the consequent loss of population immunity, and sustained drug pressure, it is important to monitor Gambian P. falciparum populations for further signs of adaptation.
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