Johannesson Hanna, Townsend Jeffrey P, Hung Chiung-Yu, Cole Garry T, Taylor John W
Department of Evolution, Genomics and Systematics, Evolutionary Biology Centre, Uppsala University, Sweden.
Genetics. 2005 Sep;171(1):109-17. doi: 10.1534/genetics.105.040923. Epub 2005 Jun 18.
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.
使病原体能够逃避宿主免疫反应的基因组动态变化，对于我们理解宿主与病原体之间的相互作用至关重要。在此，我们首次开展了一项基于群体的研究，聚焦于蛋白质编码基因重复结构域的协同进化过程。该基因SOWgp编码人类致病真菌球孢子菌和波萨达斯球孢子菌寄生阶段的免疫显性蛋白。我们对代表这两种球孢子菌地理分布范围的菌株的整个基因进行了测序。通过系统发育和遗传距离分析，我们发现SOWgp的重复部分通过协同进化而演变，主要是通过不等交换机制。我们应用了最初为多基因家族开发的数学模型，来估计重复序列阵列的同质化和重组率，结果表明，协同进化模式是重复单元以接近核苷酸点突变率的速度进行同质化的结果。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，病原体通过增强误导宿主免疫系统的能力，从SOWgp重复结构域的协同进化中获益。
