Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Mol Phylogenet Evol. 2013 Apr;67(1):123-8. doi: 10.1016/j.ympev.2013.01.002. Epub 2013 Jan 19.
The kinetoplastids are an important group of protozoa from the Excavata supergroup, and cause numerous diseases with wide environmental, economic and ecological impact. Trypanosoma brucei, the causative agent of human African trypanosomiasis, expresses a dense variant surface glycoprotein (VSG) coat, facilitating immune evasion via rapid switching and antigenic variation. Coupled to VSG switching is efficient clathrin-mediated endocytosis (CME), which removes anti-VSG antibody from the parasite surface. While the precise molecular basis for an extreme CME flux is unknown, genes encoding the AP2 complex, central to CME in most organisms, are absent from T. brucei, suggesting a mechanistic divergence in trypanosome CME. Here we identify the AP complex gene cohorts of all available kinetoplastid genomes and a new Trypanosoma grayi genome. We find multiple secondary losses of AP complexes, but that loss of AP2 is restricted to T. brucei and closest relatives. Further, loss of AP2 correlates precisely with the presence of VSG genes, supporting a model whereby these two adaptations may function synergistically in immune evasion.
动基体生物是原生动物的一个重要类群，属于外质体超群，会引起许多疾病，对环境、经济和生态都有广泛影响。导致人类非洲锥虫病的布氏锥虫表达密集的变异表面糖蛋白（VSG）衣壳，通过快速转换和抗原变异来促进免疫逃避。与 VSG 转换相关的是有效的网格蛋白介导的内吞作用（CME），该作用将抗 VSG 抗体从寄生虫表面去除。虽然对于极端 CME 通量的确切分子基础尚不清楚，但编码 AP2 复合物的基因是大多数生物体中 CME 的核心，在布氏锥虫中缺失，表明锥虫 CME 的机制发生了分歧。在这里，我们鉴定了所有可用的动基体生物基因组和一个新的格氏锥虫基因组中的 AP 复合物基因群。我们发现了多个 AP 复合物的次生性缺失，但 AP2 的缺失仅限于布氏锥虫及其最亲近的亲缘关系。此外，AP2 的缺失与 VSG 基因的存在精确相关，支持了这两种适应性可能在免疫逃避中协同作用的模型。
