Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Infect Genet Evol. 2021 Aug;92:104908. doi: 10.1016/j.meegid.2021.104908. Epub 2021 May 8.
Plasmodium parasites, the cause of malaria, have a complex life cycle, infecting alternatively vertebrate hosts and female Anopheles mosquitoes and undergoing intra- and extra-cellular development in several organs of these hosts. Most of the ~5000 protein-coding genes present in Plasmodium genomes are only expressed at specific life stages, and different genes might therefore be subject to different selective pressures depending on the biological activity of the parasite and its microenvironment at this point in development. Here, we estimate the selective constraints on the protein-coding sequences of all annotated genes of rodent and primate Plasmodium parasites and, using data from scRNA-seq experiments spanning many developmental stages, analyze their variation with regard to when these genes are expressed in the parasite life cycle. Our study reveals extensive variation in selective constraints throughout the parasites' development and highlights stages that are evolving more rapidly than others. These findings provide novel insights into the biology of these parasites and could provide important information to develop better treatment strategies or vaccines against these medically-important organisms.
疟原虫寄生虫是疟疾的病原体，具有复杂的生命周期，交替感染脊椎动物宿主和雌性按蚊，并在这些宿主的几个器官中经历细胞内和细胞外发育。在疟原虫基因组中存在的约 5000 个编码蛋白的基因中，大多数仅在特定的生命阶段表达，因此，不同的基因可能会受到不同的选择压力，具体取决于寄生虫在发育过程中的生物活性及其微环境。在这里，我们估计了啮齿动物和灵长类疟原虫寄生虫所有注释基因的编码序列的选择约束，并利用来自跨越许多发育阶段的 scRNA-seq 实验的数据，分析了它们与寄生虫生命周期中何时表达这些基因的关系。我们的研究揭示了寄生虫发育过程中选择约束的广泛变化，并强调了比其他阶段进化更快的阶段。这些发现为这些寄生虫的生物学提供了新的见解，并为开发针对这些具有重要医学意义的生物体的更好的治疗策略或疫苗提供了重要信息。
