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Concerted Evolution in the Repeats of an Immunomodulating Cell Surface Protein, SOWgp, of the Human Pathogenic Fungi Coccidioides immitis and C. posadasii

机译:人类致病性真菌球虫免疫和C. posadasii的免疫调节细胞表面蛋白SOWgp重复序列中的协调进化。

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摘要

Genome dynamics that allow pathogens to escape host immune responses are fundamental to our understanding of host-pathogen interactions. Here we present the first population-based study of the process of concerted evolution in the repetitive domain of a protein-coding gene. This gene, SOWgp, encodes the immunodominant protein in the parasitic phase of the human pathogenic fungi Coccidioides immitis and C. posadasii. We sequenced the entire gene from strains representing the geographic ranges of the two Coccidioides species. By using phylogenetic and genetic distance analyses we discovered that the repetitive part of SOWgp evolves by concerted evolution, predominantly by the mechanism of unequal crossing over. We implemented a mathematical model originally developed for multigene families to estimate the rate of homogenization and recombination of the repetitive array, and the results indicate that the pattern of concerted evolution is a result of homogenization of repeat units proceeding at a rate close to the nucleotide point mutation rate. The release of the SOWgp molecules by the pathogen during proliferation may mislead the host: we speculate that the pathogen benefits from concerted evolution of repeated domains in SOWgp by an enhanced ability to misdirect the host's immune system.
机译:允许病原体逃脱宿主免疫反应的基因组动态是我们对宿主-病原体相互作用的理解的基础。在这里,我们介绍蛋白质编码基因的重复域中协调进化过程的第一个基于人群的研究。该基因SOWgp编码人致病性真菌球虫(Coccidioides immitis)和波氏梭菌(C. posadasii)寄生期的免疫优势蛋白。我们从代表两个球虫物种地理范围的菌株中测序了整个基因。通过系统发育和遗传距离分析,我们发现SOWgp的重复部分通过协调进化而进化,主要是通过不平等交叉的机制。我们实施了最初为多基因家族开发的数学模型,以估计重复阵列的均质化和重组率,结果表明,协同进化的模式是重复单元均质化的结果,均以接近核苷酸点的速率进行突变率。病原体在增殖过程中释放SOWgp分子可能会误导宿主:我们推测病原体受益于SOWgp中重复域协调一致的进化,这归因于错误定向宿主免疫系统的能力增强。

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