Co-transmission of Related Malaria Parasite Lineages Shapes Within-Host Parasite Diversity

Co-transmission of Related Malaria Parasite Lineages Shapes Within-Host Parasite Diversity
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DOI:
10.1016/j.chom.2019.12.001
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发表时间:
2020-01-08
影响因子:
30.3
通讯作者:
Cheeseman, Ian H.
Cheeseman, Ian H.
中科院分区:
医学1区
文献类型:
--
作者:
Nkhoma, Standwell C.;Trevino, Simon G.;Cheeseman, Ian H.

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在高传播地区,我们预计复杂疟疾感染中的寄生虫谱系由于不同蚊子的寄生虫接种而不相关。该项目旨在验证这一预测。我们从马拉维Chikhwawa(一个传播严重的地区)的15名恶性疟原虫疟疾患者中生成了485个单细胞基因组序列。患者体内有多达17种独特的寄生虫谱系。令人惊讶的是,感染中的寄生虫谱系往往是密切相关的,这表明重复蚊子叮咬的重复感染比单一蚊子的寄生虫共同传播更罕见。近亲和远亲的寄生虫都构成感染,这表明复杂感染在多个宿主之间的连续传播。我们确定了四分体,并重建了亲本单倍型,这揭示了感染和非孟德尔遗传的近交系祖先。我们的分析表明,在高传播环境中,疟疾寄生虫的二次感染和远系繁殖存在很大障碍,这为疟疾的生物学和传播提供了意想不到的见解。
In high-transmission regions, we expect parasite lineages within complex malaria infections to be unrelated due to parasite inoculations from different mosquitoes. This project was designed to test this prediction. We generated 485 single-cell genome sequences from fifteen P. falciparum malaria patients from Chikhwawa, Malawi-an area of intense transmission. Patients harbored up to seventeen unique parasite lineages. Surprisingly, parasite lineages within infections tend to be closely related, suggesting that superinfection by repeated mosquito bites is rarer than co-transmission of parasites from a single mosquito. Both closely and distantly related parasites comprise an infection, suggesting sequential transmission of complex infections between multiple hosts. We identified tetrads and reconstructed parental haplotypes, which revealed the inbred ancestry of infections and non-Mendelian inheritance. Our analysis suggests strong barriers to secondary infection and outbreeding amongst malaria parasites from a high transmission setting, providing unexpected insights into the biology and transmission of malaria.