The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction.

The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction.
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DOI:
10.1093/nar/gku322
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发表时间:
2014-06
影响因子:
14.9
通讯作者:
Pain A
Pain A
中科院分区:
生物学2区
文献类型:
--
作者:
Jackson AP;Otto TD;Darby A;Ramaprasad A;Xia D;Echaide IE;Farber M;Gahlot S;Gamble J;Gupta D;Gupta Y;Jackson L;Malandrin L;Malas TB;Moussa E;Nair M;Reid AJ;Sanders M;Sharma J;Tracey A;Quail MA;Weir W;Wastling JM;Hall N;Willadsen P;Lingelbach K;Shiels B;Tait A;Berriman M;Allred DR;Pain A

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巴贝斯虫属是蜱传红细胞内血液寄生虫,通过对受感染红细胞表面表达的寄生虫衍生的变异红细胞表面抗原 (VESA) 进行连续修饰,利用抗原变异来抵抗宿主免疫。我们通过三个巴贝虫物种(B. bigemina、B. divergens 和 B. bovis)内部和之间的比较分析,确定了驱动编码 VESA (ves1) 的基因抗原多样性的基因组过程。 Ves1 结构在物种形成后迅速分化,特别是通过从规范 ves1 基因 5' 端进化出缩短形式 (ves2)。系统发育分析表明,ves1 基因通常在基因座之间转位,而 ves2 基因则不然。同样,序列嵌合分析表明,重组驱动了 ves1 序列的变异,但 ves2 序列的变异较少,表明这两个家族采用了不同的变异机制。 B. bigemina PR 分离株的蛋白质组学分析表明,两种主要的 VESA1 蛋白在群体中表达,而许多 VESA2 蛋白是共表达的,这与每个家族的差异转录调控一致。因此,VESA2 蛋白是巴贝虫生物学中丰富且以前未被识别的元素,其进化动力学始终与 VESA1 不同,表明它们的功能是不同的。
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.
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