A High-Resolution View of Genome-Wide Pneumococcal Transformation

Transformation is an important mechanism of microbial evolution through which bacteria have been observed to rapidly adapt in response to clinical interventions; examples include facilitating vaccine evasion and the development of penicillin resistance in the major respiratory pathogen Streptococcus pneumoniae. To characterise the process in detail, the genomes of 124 S. pneumoniae isolates produced through in vitro transformation were sequenced and recombination events detected. Those recombinations importing the selected marker were independent of unselected events elsewhere in the genome, the positions of which were not significantly affected by local sequence similarity between donor and recipient or mismatch repair processes. However, both types of recombinations were sometimes mosaic, with multiple non-contiguous segments originating from the same molecule of donor DNA. The lengths of the unselected events were exponentially distributed with a mean of 2.3 kb, implying that recombinations are stochastically resolved with a fixed per base probability of 4.4×10−4 bp−1. This distribution of recombination sizes, coupled with an observed under representation of large insertions within transferred sequence, suggests transformation has the potential to reduce the size of bacterial genomes, and is unlikely to act as an efficient mechanism for the uptake of accessory genomic loci.

转化（Transformation）是微生物进化的重要机制，已有研究观察到细菌可通过该机制快速适应临床干预，例如帮助主要呼吸道病原体肺炎链球菌（Streptococcus pneumoniae）实现疫苗逃逸以及获得青霉素抗性。为详细解析该过程，研究人员对124株经体外转化（in vitro transformation）获得的肺炎链球菌分离株进行了基因组测序，并检测了重组事件。携带筛选标记的重组事件与基因组其他区域的非筛选重组事件相互独立，后者的位置并未因供体与受体间的局部序列同源性或错配修复过程而受到显著影响。不过，两类重组事件有时均呈嵌合状，即存在多个源自同一供体DNA分子的不连续片段。非筛选重组事件的长度呈指数分布，平均长度为2.3 kb，这表明重组事件以固定的每碱基概率4.4×10⁻⁴ bp⁻¹随机完成修复。这种重组长度分布，结合观察到的转移序列中大插入片段占比偏低的现象，表明转化机制有可能缩小细菌基因组规模，且不太可能成为获取附属基因组位点的高效途径。