Recombination-driven generation of the largest pathogen repository of antigen variants in the protozoan Trypanosoma cruzi

BMC Genomics

Research Article

Rick L. Tarleton¹  Duo Peng¹  D. Brent Weatherly² 

[1] Center for Tropical and Emerging Global Diseases, Institute of Bioinformatics and Department of Cellular Biology, University of Georgia, 30602, Athens, GA, USA;Center for Tropical and Emerging Global Diseases, Institute of Bioinformatics and Department of Cellular Biology, University of Georgia, 30602, Athens, GA, USA;Center for Complex Carbohydrate Research, University of Georgia, 30602, Athens, GA, USA;

关键词: Chagas disease;    Trans-sialidase;    Trypanosoma cruzi;    Immune evasion;    Recombination;    Antigen variants;   

DOI  :  10.1186/s12864-016-3037-z

 received in 2016-03-16, accepted in 2016-08-24,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe protozoan parasite Trypanosoma cruzi, causative agent of Chagas disease, depends upon a cell surface-expressed trans-sialidase (ts) to avoid activation of complement-mediated lysis and to enhance intracellular invasion. However these functions alone fail to account for the size of this gene family in T. cruzi, especially considering that most of these genes encode proteins lacking ts enzyme activity. Previous whole genome sequencing of the CL Brener clone of T. cruzi identified ~1400 ts variants, but left many partially assembled sequences unannotated.ResultsIn the current study we reevaluated the trans-sialidase-like sequences in this reference strain, identifying an additional 1779 full-length and partial ts genes with their important features annotated, and confirming the expression of previously annotated “pseudogenes” and newly annotated ts family members. Multiple EM for Motif Elicitation (MEME) analysis allowed us to generate a model T. cruzi ts (TcTS) based upon the most conserved motif patterns and demonstrated that a common motif order is highly conserved among ts family members. Using a newly developed pipeline for the analysis of recombination within large gene families, we further demonstrate that TcTS family members are undergoing frequent recombination, generating new variants from the thousands of functional and non-functional ts gene segments but retaining the overall structure of the core TcTS family members.ConclusionsThe number and variety as well as high recombination frequency of TcTS family members supports strong evolutionary pressure, probably exerted by immune selection, for continued variation in ts sequences in T. cruzi, and thus for a unique immune evasion mechanism for the large ts gene family.

【 授权许可】

CC BY   
© The Author(s). 2016