Evolution of Chlamydia trachomatis diversity occurs by widespread interstrain recombination involving hotspots
Evolution of Chlamydia trachomatis diversity occurs by widespread interstrain recombination involving hotspots
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DOI：
10.1101/gr.5674706
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发表时间：
2007-01-01
期刊：
影响因子：
7
通讯作者：
Dean, Deborah
中科院分区：
文献类型：
--
作者：
Gomes, Joao P.;Bruno, William J.;Dean, Deborah
沙眼衣原体是一种具有重大公共卫生意义的专性细胞内细菌，感染了世界上超过十分之一的人口，并导致数百万人失明和不育。越来越多的证据支持重组是自由生活细菌间遗传多样性的关键来源。先前的研究表明，衣原体等细胞内细菌也可能发生重组，但这是否在进化中起重要作用尚未确定。在此，我们检测了分布在整个染色体上的多个基因座，通过系统发育重建、相容性矩阵以及基于统计学的重组程序，确定了19个实验室参考菌株以及10个当代眼部和泌尿生殖道临床分离株之间重组的程度和意义。重组现象很普遍；所有临床分离株在多个基因座上都是重组的，没有两个属于同一克隆谱系。几个参考菌株在不同基因座上显示出不一致的系统发育关系；一个菌株被明确鉴定为是由其他参考菌株谱系重组而来。频繁的重组与低水平的点突变形成对比；相对于参考菌株，每千个碱基中出现的新突变少于一个。在编码主要外膜蛋白的ompA基因下游确定了重组热点。这种对于细胞内细菌来说出乎意料的广泛重组，解释了为什么使用一两个基因（如ompA）进行菌株分型与临床表型不相关。我们的研究结果没有指出导致不同致病性的具体事件，而是提出了一种剖析临床菌株病理遗传基础的新方法，这对进化、宿主细胞适应以及新的衣原体疾病的出现具有启示意义。
Chlamydia trachomatis is an obligate intracellular bacterium of major public health significance, infecting over one-tenth of the world's population and causing blindness and infertility in millions. Mounting evidence supports recombination as a key source of genetic diversity among free-living bacteria. Previous research shows that intracellular bacteria such as Chlamydiaceae may also undergo recombination but whether this plays a significant evolutionary role has not been determined. Here, we examine multiple loci dispersed throughout the chromosome to determine the extent and significance of recombination among 19 laboratory reference strains and 10 present-day ocular and urogenital clinical isolates using phylogenetic reconstructions, compatibility matrices, and statistically based recombination programs. Recombination is widespread; all clinical isolates are recombinant at multiple loci with no two belonging to the same clonal lineage. Several reference strains show nonconcordant phylogenies across loci; one strain is unambiguously identified as recombinantly derived from other reference strain lineages. Frequent recombination contrasts with a low level of point substitution; novel substitutions relative to reference strains occur less than one per kilobase. Hotspots for recombination are identified downstream from ompA, which encodes the major outer membrane protein. This widespread recombination, unexpected for an intracellular bacterium, explains why strain-typing using one or two genes, such as ompA, does not correlate with clinical phenotypes. Our results do not point to specific events that are responsible for different pathogenicities but, instead, suggest a new approach to dissect the genetic basis for clinical strain pathology with implications for evolution, host cell adaptation, and emergence of new chlamydial diseases.