Evolution of transcriptional control of antigenic variation and virulence in human and ape malaria parasites.
Evolution of transcriptional control of antigenic variation and virulence in human and ape malaria parasites.
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DOI：
10.1186/s12862-021-01872-z
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发表时间：
2021-07-08
影响因子：
2.2
通讯作者：
Deitsch KW
中科院分区：
文献类型：
--
作者：
Gross MR;Hsu R;Deitsch KW
最严重的人类疟疾是由原生动物寄生虫恶性疟原虫引起的。这种单细胞生物是感染猿类的疟原虫亚属的成员，恶性疟原虫是唯一感染人类的成员。该物种对人类的特殊毒力很大程度上归因于寄生虫将一系列变异表面抗原置于受感染红细胞表面，介导对血管内皮的粘附。这些蛋白质由一个名为 var 的大型多拷贝基因家族编码，每个 var 基因编码不同形式的蛋白质。通过改变 var 基因的表达，寄生虫可以避免免疫识别，这一过程称为抗原变异，是疟疾感染慢性本质的基础。在这里，我们表明，包括人类寄生虫在内的 Laverania 谱系分支的共同祖先在与 var 基因家族显示的复杂转录调控相关的元件的组织和结构方面经历了显着的变化。与 Laverania 的其他成员不同，产生恶性疟原虫的进化枝进化出了不同的 var 基因子集，这些子集可通过不同的上游转录调控区来区分，这些转录调控区与不同的表达谱和毒力特性相关。此外，两个独特保守的 var 基因被认为在协调转录转换中发挥作用，同样在该进化枝中独特出现。我们假设这些变化起源于非洲大陆气候剧烈变化的时期，预计这将导致传播动态发生重大变化，从而选择抗原变异模式，从而实现更长时间、更慢性的感染。这些观察结果表明，传播动力学的变化选择了介导包括恶性疟原虫在内的寄生虫谱系中抗原变异的转录调节机制的显着改变。这些变化可能是这些感染的慢性性质及其异常毒力的基础。在线版本包含可在 10.1186/s12862-021-01872-z 获取的补充材料。
The most severe form of human malaria is caused by the protozoan parasite Plasmodium falciparum. This unicellular organism is a member of a subgenus of Plasmodium called the Laverania that infects apes, with P. falciparum being the only member that infects humans. The exceptional virulence of this species to humans can be largely attributed to a family of variant surface antigens placed by the parasites onto the surface of infected red blood cells that mediate adherence to the vascular endothelium. These proteins are encoded by a large, multicopy gene family called var, with each var gene encoding a different form of the protein. By changing which var gene is expressed, parasites avoid immune recognition, a process called antigenic variation that underlies the chronic nature of malaria infections. Here we show that the common ancestor of the branch of the Laverania lineage that includes the human parasite underwent a remarkable change in the organization and structure of elements linked to the complex transcriptional regulation displayed by the var gene family. Unlike the other members of the Laverania, the clade that gave rise to P. falciparum evolved distinct subsets of var genes distinguishable by different upstream transcriptional regulatory regions that have been associated with different expression profiles and virulence properties. In addition, two uniquely conserved var genes that have been proposed to play a role in coordinating transcriptional switching similarly arose uniquely within this clade. We hypothesize that these changes originated at a time of dramatic climatic change on the African continent that is predicted to have led to significant changes in transmission dynamics, thus selecting for patterns of antigenic variation that enabled lengthier, more chronic infections. These observations suggest that changes in transmission dynamics selected for significant alterations in the transcriptional regulatory mechanisms that mediate antigenic variation in the parasite lineage that includes P. falciparum. These changes likely underlie the chronic nature of these infections as well as their exceptional virulence. The online version contains supplementary material available at 10.1186/s12862-021-01872-z.
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影响因子：
4.8
作者：
Calderwood, MS;Gannoun-Zaki, L;Deitsch, KW
通讯作者：
Deitsch, KW
影响因子：
6.7
作者：
Barry AE;Leliwa-Sytek A;Tavul L;Imrie H;Migot-Nabias F;Brown SM;McVean GA;Day KP
通讯作者：
Day KP
影响因子：
6.4
作者：
Bryant JM;Regnault C;Scheidig-Benatar C;Baumgarten S;Guizetti J;Scherf A
通讯作者：
Scherf A
影响因子：
2.4
作者：
Kaur, Chhaminder;Kumar, Mayank;Patankar, Swati
通讯作者：
Patankar, Swati
影响因子：
64.8
作者：
Deitsch, KW;Calderwood, MS;Wellems, TE
通讯作者：
Wellems, TE