Strain-specific genome evolution in Trypanosoma cruzi, the agent of Chagas disease.
Strain-specific genome evolution in Trypanosoma cruzi, the agent of Chagas disease.
复制标题
DOI：
10.1371/journal.ppat.1009254
复制
发表时间：
2021-01
期刊：
影响因子：
6.7
通讯作者：
Tarleton RL
中科院分区：
文献类型：
--
作者：
Wang W;Peng D;Baptista RP;Li Y;Kissinger JC;Tarleton RL
The protozoan Trypanosoma cruzi almost invariably establishes life-long infections in humans and other mammals, despite the development of potent host immune responses that constrain parasite numbers. The consistent, decades-long persistence of T. cruzi in human hosts arises at least in part from the remarkable level of genetic diversity in multiple families of genes encoding the primary target antigens of anti-parasite immune responses. However, the highly repetitive nature of the genome–largely a result of these same extensive families of genes–have prevented a full understanding of the extent of gene diversity and its maintenance in T. cruzi. In this study, we have combined long-read sequencing and proximity ligation mapping to generate very high-quality assemblies of two T. cruzi strains representing the apparent ancestral lineages of the species. These assemblies reveal not only the full repertoire of the members of large gene families in the two strains, demonstrating extreme diversity within and between isolates, but also provide evidence of the processes that generate and maintain that diversity, including extensive gene amplification, dispersion of copies throughout the genome and diversification via recombination and in situ mutations. Gene amplification events also yield significant copy number variations in a substantial number of genes presumably not required for or involved in immune evasion, thus forming a second level of strain-dependent variation in this species. The extreme genome flexibility evident in T. cruzi also appears to create unique challenges with respect to preserving core genome functions and gene expression that sets this species apart from related kinetoplastids. Many pathogens vary their surface antigenic profile in order to establish and maintain infections in the face of host immune responses. Although antigenic variation has been extensively documented in extracellular pathogens and is crucial in these cases to pathogen evasion of host antibody responses, there is scant understanding of the role that antigenic variation plays in immunity to intracellular pathogens, where cell-mediated immune responses are key to infection control and where a low frequency of switching from one predominant surface antigen to a new variant would be expected to have little impact on immune recognition. Herein we use comparative genome analysis to reveal the details of and mechanisms behind how the intracellular parasite Trypanosoma cruzi, agent of human Chagas disease, maintains a vast and varying array of antigens that are the targets of host immune responses. The process of diversification is so efficient that two isolates share not a single identical gene among the thousands of antigenic variants in their genomes, thus making the likelihood of generating protective vaccines, low. This genome flexibility also ensnares genes whose products are not targets of immune responses, thus further driving the isolate-specific biological diversity that characterizes this species.
登录
查看更多内容
影响因子：
4.6
作者：
Callejas-Hernández F;Rastrojo A;Poveda C;Gironès N;Fresno M
通讯作者：
Fresno M
影响因子：
--
作者：
Ekanayake, Dilrukshi;Sabatini, Robert
通讯作者：
Sabatini, Robert
影响因子：
3.9
作者：
Berna, Luisa;Rodriguez, Matias;Robello, Carlos
通讯作者：
Robello, Carlos
影响因子：
1.5
作者：
Branche, C;Ochaya, S;Andersson, B
通讯作者：
Andersson, B
影响因子：
3.8
作者：
Flores-López CA;Machado CA
通讯作者：
Machado CA