Capturing the variant surface glycoprotein repertoire (the VSGnome) of Trypanosoma brucei Lister 427

被引:134
作者
Cross, George A. M. [1 ]
Kim, Hee-Sook [1 ]
Wickstead, Bill [2 ]
机构
[1] Rockefeller Univ, Mol Parasitol Lab, New York, NY 10065 USA
[2] Univ Nottingham, Queens Med Ctr, Sch Med, Nottingham NG7 2UH, England
基金
英国生物技术与生命科学研究理事会; 美国国家卫生研究院;
关键词
Antigenic variation; Variant surface glycoprotein; Codon-usage bias; Minichromosome; Expression site; Metacyclic expression site; VSG EXPRESSION SITE; AFRICAN TRYPANOSOMES; ANTIGENIC VARIATION; MEGABASE CHROMOSOMES; GEL-ELECTROPHORESIS; SEQUENCE DIVERGENCE; MOLECULAR KARYOTYPE; GENE CONVERSION; POINT MUTATIONS; METACYCLIC VSG;
D O I
10.1016/j.molbiopara.2014.06.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Trypanosoma brucei evades the adaptive immune response through the expression of antigenically distinct Variant Surface Glycoprotein (VSG) coats. To understand the progression and mechanisms of VSG switching, and to identify the VSGs expressed in populations of trypanosomes, it is desirable to predetermine the available repertoire of VSG genes (the 'VSGnome'). To date, the catalog of VSG genes present in any strain is far from complete and the majority of current information regarding VSGs is derived from the TREU927 strain that is not commonly used as an experimental model. We have assembled, annotated and analyzed 2563 distinct and previously unsequenced genes encoding complete and partial VSGs of the widely used Lister 427 strain of T. brucei. Around 80% of the VsGnome consists of incomplete genes or pseudogenes. Read-depth analysis demonstrated that most VSGs exist as single copies, but 360 exist as two or more indistinguishable copies. The assembled regions include five functional metacyclic VSG expression sites. One third of minichromosome sub-telomeres contain a VSG (64-67 VSGs on similar to 96 minichromosomes), of which 85% appear to be functionally competent. The minichromosomal repertoire is very dynamic, differing among clones of the same strain. Few VSGs are unique along their entire length: frequent recombination events are likely to have shaped (and to continue to shape) the repertoire. In spite of their low sequence conservation and short window of expression, VSGs show evidence of purifying selection, with similar to 40% of non-synonymous mutations being removed from the population. VSGs show a strong codon-usage bias that is distinct from that of any other group of trypanosome genes. VSG sequences are generally very divergent between Lister 427 and TREU927 strains of T. brucei, but those that are highly similar are not found in 'protected' genomic environments, but may reflect genetic exchange among populations. (C) 2014 The Authors. Published by Elsevier B.V.
引用
收藏
页码:59 / 73
页数:15
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