Differential accumulation of mutations localized in particular domains of the mucin genes expressed in the vertebrate host stage of Trypanosoma cruzi

Differential accumulation of mutations localized in particular domains of the mucin genes expressed in the vertebrate host stage of Trypanosoma cruzi
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DOI:
10.1016/j.molbiopara.2003.09.006
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发表时间:
2004-01-01
影响因子:
1.5
通讯作者:
Frasch, ACC
Frasch, ACC
中科院分区:
医学4区
文献类型:
--
作者:
Campo, V;Di Noia, JM;Frasch, ACC

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克氏锥虫的表面覆盖着与寄生虫保护、附着和免疫逃避有关的粘蛋白型糖蛋白。脊椎动物寄生虫表达的粘蛋白基因家族TcMUC由数百个成员组成,具有很高的变异性。在昆虫寄生阶段表达的粘蛋白编码基因属于一个同源性更高的家族,称为TcSMUG。在这里,我们讨论了物理连接的T ruzi粘蛋白基因的组织和进化,方法是对包含这些基因的大染色体片段进行测序。突变的特定积累被限制在TcMUC基因的特定区域,表明这些区域已经或曾经有过加速的进化速度。通过对几个TcMUC基因的序列分析,可以确定TcMUC I和TcMUC 11的共同特征,从而证明一组基因是由另一组基因产生的。TcMUC和TcSMUG家族高度保守的基因间隔区都含有富含甘油三酯的微卫星,这些微卫星在粘粒中的无关基因中不存在,这表明同源重组在T CRUZI粘蛋白基因的改组和/或扩增中发挥了作用。TcMUC II基因的同源序列比较表明,它们的中心可变区是保守的。这种保守性在DNA水平上总是更高,这表明在TcMUC 11基因的这些特定区域进行了正选择。(C)2003爱思唯尔B.V.保留所有权利。
The surface of Trypanosoma cruzi is covered by mucin-type glycoproteins involved in parasite protection, attachment and immunoevasion. The gene family coding for the mucins expressed by the parasite in the vertebrate host, named TcMUC, is composed of several hundred members and presents high variability. The genes encoding mucins expressed in the insect-dwelling parasite stages are part of a much more homogeneous family, named TcSMUG. Here, we addressed the organization and evolution of physically linked T cruzi mucin genes by sequencing large chromosomal fragments containing these genes. Specific accumulation of mutations was restricted to particular domains of TcMUC genes, showing that these regions have, or have had, an accelerated evolution rate. Sequence analysis of several TcMUC genes allowed for the identification of members sharing features of TcMUC I and 11, thus evidencing that one group of genes was generated from the other. The highly conserved intergenic regions of both TcMUC and TcSMUG families contained TG-rich microsatellites that were not present in unrelated genes in the cosmids, suggesting a role for homologous recombination in shuffling and/or amplification of T cruzi mucin genes. The comparison of putative homologous TcMUC II genes from different strains of T cruzi showed that their central variable domains are conserved. This conservation was always higher at the DNA level suggesting positive selection in these particular regions of TcMUC 11 genes. (C) 2003 Elsevier B.V. All rights reserved.