Genomic epidemiology of artemisinin resistant malaria
Genomic epidemiology of artemisinin resistant malaria
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DOI：
10.7554/elife.08714
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发表时间：
2016-03-04
期刊：
影响因子：
7.7
通讯作者：
Kwiatkowski, Dominic P.
中科院分区：
文献类型：
--
作者：
Amato, Roberto;Miotto, Olivo;Kwiatkowski, Dominic P.
目前在东南亚流行的青蒿素耐药恶性疟原虫是软选择性扫描的结果，涉及至少20个独立的kelch 13突变。在一项大型的全球调查中，我们发现在东南亚引起耐药性的kelchl3突变在非洲的频率很低。我们发现，非洲kelch13突变起源于当地，和kelch13显示正常的变异模式相对于其他基因在非洲，而在东南亚有大量的非同义突变，其中许多导致激进的氨基酸变化。因此，kelch 13目前在非洲没有经历强烈的选择，尽管有很深的变异库，可能会使耐药性迅速出现。实际意义是，青蒿素耐药性的公共卫生监测不应仅依赖于kelchl3数据，预防耐药性的干预措施必须考虑到当地的进化条件，基因组流行病学显示地理区域之间存在很大差异。
The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelchl3 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 mutations have originated locally, and that kelch13 shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus, kelch13 is not currently undergoing strong selection in Africa, despite a deep reservoir of variations that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely on kelchl3 data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions.