Gunarathna Isuru, Spear Joseph D, Carter Tamar E
Baylor University.
Res Sq. 2024 Oct 30:rs.3.rs-5040478. doi: 10.21203/rs.3.rs-5040478/v1.
The high burden of malaria in Africa is largely due to the presence of competent and adapted vector species. With invasive implicated in malaria outbreaks in Africa, understanding the genomic basis of vector-parasite compatibility is essential for assessing the risk of future outbreaks due to this mosquito. Vector compatibility with arises from ancient coevolution and involves genes like in and P47Rec in . Questions remain about whether sub-continental vector variation is a selective pressure on current populations or not.
We analyzed the genetic diversity in parasite-vector interaction genes in and from 9 and 15 countries in Africa, respectively. Specifically, we looked for evidence of malaria vector-mediated selection within three genes and conducted association analyses with occurrence probabilities of prominent malaria vectors (VOP).
Higher protein haplotype diversities of Pfs47 and Pfs16 were associated with the probability of occurrence of and together. Only carried a signature of positive selection consistently (average Tajima's D = -2.96) which was associated with the probability of occurrence of . These findings support vector-mediated selection based on vector species diversity may be occurring within Africa. We also employed phylogenetic analyses of interaction genes (, , ) to identify significant subspecies diversity as a prerequisite to vector-population-mediated selection. HPX15 revealed significant sub-species differentiation (multiple branches bootstrap >70) compared to absence of variation in P47Rec, suggesting further investigation into sub-species mediated selection based on HPX15 is needed. Finally, we observed five amino acid changes at P47Rec in invasive compared to dominant African species, calling for further investigation of the impact these distinct P47Rec variants would have on local African Pfs47 diversity.
Overall, these findings support the notion that vector variation within Africa could influence diversity and lay a genomic framework for future investigation of invasive impact on African malaria.
非洲疟疾负担沉重，很大程度上是由于存在有传播能力且适应性良好的病媒物种。随着外来物种与非洲疟疾疫情有关联，了解病媒 - 寄生虫相容性的基因组基础对于评估由这种蚊子引发未来疫情的风险至关重要。病媒与寄生虫的相容性源于古老的共同进化，涉及如按蚊中的Pfs47和冈比亚按蚊中的P47Rec等基因。关于次大陆病媒变异是否对当前疟原虫种群构成选择压力，仍存在疑问。
我们分别分析了来自非洲9个和15个国家的冈比亚按蚊和阿拉伯按蚊中寄生虫 - 病媒相互作用基因的遗传多样性。具体而言，我们在三个疟原虫基因（Pfs47、Pfs16和P47Rec）中寻找疟疾病媒介导选择的证据，并对主要疟疾病媒（VOP）的出现概率进行关联分析。
Pfs47和Pfs16较高的蛋白质单倍型多样性与冈比亚按蚊和阿拉伯按蚊共同出现的概率相关。只有P47Rec始终带有正选择的特征（平均Tajima's D = -2.96），这与冈比亚按蚊的出现概率相关。这些发现支持基于病媒物种多样性的病媒介导选择可能正在非洲发生。我们还对疟原虫相互作用基因（Pfs47、Pfs16、P47Rec）进行了系统发育分析，以确定显著的亚种多样性是病媒 - 种群介导选择的先决条件。与P47Rec缺乏变异相比，HPX15显示出显著的亚种分化（多个分支自展值>70），这表明需要进一步研究基于HPX15的亚种介导选择。最后，我们观察到与占主导地位的非洲物种相比，外来阿拉伯按蚊的P47Rec有五个氨基酸变化，这需要进一步研究这些不同的P47Rec变体对当地非洲疟原虫Pfs47多样性的影响。
总体而言，这些发现支持非洲内部病媒变异可能影响多样性这一观点，并为未来研究外来阿拉伯按蚊对非洲疟疾的影响奠定了基因组框架。
