Bioinformatics and Genomics, University of North Carolina, Charlotte, NC, United States.
Biological Sciences, University of North Carolina, Charlotte, NC, United States.
Front Cell Infect Microbiol. 2022 Jan 13;11:789417. doi: 10.3389/fcimb.2021.789417. eCollection 2021.
The unique biological features of not only make it difficult to control but also to eliminate. For the transmission of the malaria parasite from infected human to the vector, gametocytes play a major role. The transmission potential of a malarial infection is inferred based on microscopic detection of gametocytes and molecular screening of genes in the female gametocytes. Microscopy-based detection methods could grossly underestimate the reservoirs of infection as gametocytes may occur as submicroscopic or as micro- or macro-gametocytes. The identification of genes that are highly expressed and polymorphic in male and female gametocytes is critical for monitoring changes not only in their relative proportions but also the composition of gametocyte clones contributing to transmission over time. Recent transcriptomic study revealed two distinct clusters of highly correlated genes expressed in the gametocytes, indicating that the male and female terminal gametocytogeneses are independently regulated. However, the detective power of these genes is unclear. In this study, we compared genetic variations of 15 and 11 genes expressed, respectively, in the female and male gametocytes among isolates from Southeast Asia, Africa, and South America. Further, we constructed phylogenetic trees to determine the resolution power and clustering patterns of gametocyte clones. As expected, 25 (PVP01_0616100) and 16 (PVP01_0305600) expressed in the female gametocytes were highly conserved in all geographical isolates. In contrast, genes including 6-cysteine protein (PVP01_0415800) and upregulated in late gametocytes (PVP01_1452800) expressed in the female gametocytes, as well as two CPW-WPC family proteins (PVP01_1215900 and PVP01_1320100) expressed in the male gametocytes indicated considerably high nucleotide and haplotype diversity among isolates. Parasite samples expressed in male and female gametocyte genes were observed in separate phylogenetic clusters and likely represented distinct gametocyte clones. Compared to 25, (PVP01_0415800) and a CPW-WPC family protein (PVP01_0904300) showed higher expression in a subset of Ethiopian samples. Thus, , , and CPW-WPC family proteins including PVP01_0904300, PVP01_1215900, and PVP01_1320100 could potentially be used as novel biomarkers for detecting both sexes of gametocytes in low-density infections and estimating transmission reservoirs.
疟原虫不仅具有独特的生物学特征，难以控制，而且难以消除。疟原虫配子体对于从受感染的人类向媒介传播疟疾寄生虫起着主要作用。疟疾感染的传播潜力是基于对配子体的显微镜检测和雌性配子体基因的分子筛选来推断的。基于显微镜的检测方法可能会大大低估感染的储存库，因为配子体可能表现为亚微观或微观或宏观配子体。鉴定在雄性和雌性配子体中高度表达和多态的基因对于监测它们的相对比例以及随时间推移有助于传播的配子体克隆的组成变化至关重要。最近的转录组研究揭示了在疟原虫配子体中表达的两个截然不同的高度相关基因簇，表明雄性和雌性配子体终末发生是独立调节的。然而，这些基因的检测能力尚不清楚。在这项研究中，我们比较了来自东南亚、非洲和南美洲的分离株中分别在雌性和雄性配子体中表达的 15 个和 11 个基因的遗传变异。此外，我们构建了系统发育树来确定配子体克隆的分辨率和聚类模式。正如预期的那样，在所有地理分离株中，在雌性配子体中表达的 25 （PVP01_0616100）和 16 （PVP01_0305600）高度保守。相比之下，在雌性配子体中表达的包括 6-半胱氨酸蛋白（PVP01_0415800）和晚期配子体中上调的 （PVP01_1452800）以及在雄性配子体中表达的两个 CPW-WPC 家族蛋白（PVP01_1215900 和 PVP01_1320100）在分离株中显示出相当高的核苷酸和单倍型多样性。在雄性和雌性配子体基因中表达的寄生虫样本观察到在单独的系统发育聚类中，可能代表不同的配子体克隆。与 25 相比，（PVP01_0415800）和一个 CPW-WPC 家族蛋白（PVP01_0904300）在埃塞俄比亚的一部分样本中显示出更高的表达。因此， 、 、和包括 PVP01_0904300、PVP01_1215900 和 PVP01_1320100 的 CPW-WPC 家族蛋白可能潜在地用作检测低密度感染中两性配子体和估计传播储存库的新型生物标志物。
