School of Biosciences, The University of Melbourne, Parkville, VIC 3052, Australia;
Department of Microbiology, New York University, New York, NY 10016.
Proc Natl Acad Sci U S A. 2017 May 16;114(20):E4103-E4111. doi: 10.1073/pnas.1613018114. Epub 2017 May 1.
Existing theory on competition for hosts between pathogen strains has proposed that immune selection can lead to the maintenance of strain structure consisting of discrete, weakly overlapping antigenic repertoires. This prediction of strain theory has conceptual overlap with fundamental ideas in ecology on niche partitioning and limiting similarity between coexisting species in an ecosystem, which oppose the hypothesis of neutral coexistence. For , strain theory has been specifically proposed in relation to the major surface antigen of the blood stage, known as EMP1 and encoded by the multicopy multigene family known as the genes. Deep sampling of the DBLα domain of genes in the local population of Bakoumba, West Africa, was completed to define whether patterns of repertoire overlap support a role of immune selection under the opposing force of high outcrossing, a characteristic of areas of intense malaria transmission. Using a 454 high-throughput sequencing protocol, we report extremely high diversity of the DBLα domain and a large parasite population with DBLα repertoires structured into nonrandom patterns of overlap. Such population structure, significant for the high diversity of genes that compose it at a local level, supports the existence of "strains" characterized by distinct gene repertoires. Nonneutral, frequency-dependent competition would be at play and could underlie these patterns. With a computational experiment that simulates an intervention similar to mass drug administration, we argue that the observed repertoire structure matters for the antigenic diversity of the parasite population remaining after intervention.
现有的病原体菌株间宿主竞争理论提出,免疫选择可导致由离散的、弱重叠抗原库组成的菌株结构得以维持。该菌株理论的预测与生态学中关于生态系统中生态位分割和共存物种间限制相似性的基本理念存在概念上的重叠,而这些理念与中性共存假说相矛盾。具体而言,菌株理论是针对血阶段的主要表面抗原提出的,这种抗原被称为 EMP1,由称为“”基因的多拷贝多基因家族编码。在西非 Bakoumba 当地人群中,对“”基因的 DBLα 结构域进行了深度采样,以确定在高杂交(疟疾传播活跃地区的特征)的反向作用力下,库重叠模式是否支持免疫选择的作用。我们使用 454 高通量测序方案,报告了 DBLα 结构域的极高多样性,以及具有 DBLα 库的大型寄生虫种群,其库结构呈现出非随机的重叠模式。这种种群结构对于构成其的“”基因的高度多样性具有重要意义,支持了具有独特“”基因库的“菌株”的存在。非中性、频率依赖的竞争将发挥作用,并可能是这些模式的基础。通过模拟类似于大规模药物干预的计算实验,我们认为观察到的库结构对于干预后寄生虫种群的抗原多样性很重要。