Jackson Andrew P, Otto Thomas D, Darby Alistair, Ramaprasad Abhinay, Xia Dong, Echaide Ignacio Eduardo, Farber Marisa, Gahlot Sunayna, Gamble John, Gupta Dinesh, Gupta Yask, Jackson Louise, Malandrin Laurence, Malas Tareq B, Moussa Ehab, Nair Mridul, Reid Adam J, Sanders Mandy, Sharma Jyotsna, Tracey Alan, Quail Mike A, Weir William, Wastling Jonathan M, Hall Neil, Willadsen Peter, Lingelbach Klaus, Shiels Brian, Tait Andy, Berriman Matt, Allred David R, Pain Arnab
Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park Ic2, 146 Brownlow Hill, Liverpool L3 5RF, UK
Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Nucleic Acids Res. 2014 Jun;42(11):7113-31. doi: 10.1093/nar/gku322. Epub 2014 May 5.
Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5' ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct.
巴贝斯虫属是蜱传播的红细胞内血寄生虫，通过对感染红细胞表面表达的源自寄生虫的变异红细胞表面抗原（VESA）进行顺序修饰，利用抗原变异来抵抗宿主免疫。我们通过对三种巴贝斯虫（双芽巴贝斯虫、分歧巴贝斯虫和牛巴贝斯虫）内部及之间的比较分析，确定了驱动VESA编码基因（ves1）抗原多样性的基因组过程。Ves1结构在物种形成后迅速分化，特别是通过从典型ves1基因的5'端进化出缩短形式（ves2）。系统发育分析表明，ves1基因经常在基因座之间转座，而ves2基因则不然。同样，序列镶嵌分析表明，重组驱动ves1序列的变异，但对ves2的驱动作用较小，这表明两个家族采用了不同的变异机制。对双芽巴贝斯虫PR分离株的蛋白质组分析表明，群体中表达两种主要的VESA1蛋白，而大量VESA2蛋白共表达，这与每个家族的差异转录调控一致。因此，VESA2蛋白是巴贝斯虫生物学中丰富且以前未被认识的成分，其进化动态与VESA1始终不同，表明它们的功能不同。
