Duke Global Health Institute, Duke Universitygrid.26009.3d, Durham, North Carolina, USA.
School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya.
mBio. 2022 Oct 26;13(5):e0227722. doi: 10.1128/mbio.02277-22. Epub 2022 Sep 8.
Population genetic diversity of Plasmodium falciparum antigenic loci is high despite large bottlenecks in population size during the parasite life cycle. The prevalence of genetically distinct haplotypes at these loci, while well characterized in humans, has not been thoroughly compared between human and mosquito hosts. We assessed parasite haplotype prevalence, diversity, and evenness using human and mosquito P. falciparum infections collected from the same households during a 14-month longitudinal cohort study using amplicon deep sequencing of two antigenic gene fragments ( and ). To a prior set of infected humans ( = 1,175/2,813; 86.2% sequencing success) and mosquito abdomens ( = 199/1,448; 95.5% sequencing success), we added sequences from infected mosquito heads ( = 134/1,448; 98.5% sequencing success). The overall and sample-level parasite populations were more diverse in mosquitoes than in humans. Additionally, haplotype prevalences were more even in the P. falciparum human population than in the mosquito population, consistent with balancing selection occurring at these loci in humans. In contrast, we observed that infections in humans were more likely to harbor a dominant haplotype than infections in mosquitoes, potentially due to removal of unfit strains by the human immune system. Finally, within a given mosquito, there was little overlap in genetic composition of abdomen and head infections, suggesting that infections may be cleared from the abdomen during a mosquito's lifespan. Taken together, our observations provide evidence for the mosquito vector acting as a reservoir of sequence diversity in malaria parasite populations. Plasmodium falciparum is the deadliest human malaria parasite, and infections consisting of concurrent, multiple strains are common in regions of high endemicity. During transitions within and between the parasite's mosquito and human hosts, these strains are subject to population bottlenecks, and distinct parasite strains may have differential fitness in the various environments encountered. These bottlenecks and fitness differences may lead to differences in strain prevalence and diversity between hosts. We investigated differences in genetic diversity and evenness between P. falciparum parasites in human and mosquito hosts collected from the same households during a 14-month longitudinal study in Kenya. Compared to human parasite populations and infections, P. falciparum parasites observed in mosquito populations and infections were more diverse by multiple population genetic metrics. This suggests that the mosquito vector acts as a reservoir of sequence diversity in malaria parasite populations.
尽管疟原虫生活史中的种群大小存在大规模瓶颈，但疟原虫抗原基因座的种群遗传多样性仍然很高。尽管这些基因座中遗传上不同的单倍型的流行情况在人类中得到了很好的描述，但在人类和蚊子宿主之间尚未进行彻底比较。我们使用扩增子深度测序两种抗原基因片段（ 和 ），对来自同一家庭的人类和蚊子的疟原虫感染进行了寄生虫单倍型流行率、多样性和均匀度评估。对于一组先前感染的人类（ = 1,175/2,813；86.2%测序成功率）和蚊子腹部（ = 199/1,448；95.5%测序成功率），我们添加了来自感染蚊子头部的序列（ = 134/1,448；98.5%测序成功率）。总体而言，与蚊子相比，寄生虫种群在人类中的种群更为多样。此外，与蚊子种群相比，疟原虫人群中的单倍型流行率更为均匀，这与这些基因座在人类中发生平衡选择一致。相反，我们观察到人类感染比蚊子感染更有可能携带优势单倍型，这可能是由于人类免疫系统清除了不适的菌株。最后，在给定的蚊子中，腹部和头部感染的遗传组成几乎没有重叠，这表明在蚊子的生命周期中，感染可能会从腹部清除。综上所述，我们的观察结果为蚊子媒介作为疟疾寄生虫种群序列多样性库提供了证据。疟原虫是最致命的人类疟疾寄生虫，在高流行地区，同时存在多种感染的情况很常见。在寄生虫在蚊子和人类宿主之间的转变过程中，这些菌株会经历种群瓶颈，并且不同的寄生虫菌株在遇到的各种环境中可能具有不同的适应性。这些瓶颈和适应性差异可能导致宿主之间的菌株流行率和多样性存在差异。我们调查了肯尼亚一项为期 14 个月的纵向研究中从同一家庭收集的人类和蚊子宿主中疟原虫寄生虫的遗传多样性和均匀性差异。与人类寄生虫种群和感染相比，在蚊子种群和感染中观察到的疟原虫寄生虫在多个种群遗传指标上更为多样。这表明蚊子媒介是疟疾寄生虫种群中序列多样性的储存库。
