Yimer Solomon A, Namouchi Amine, Zegeye Ephrem Debebe, Holm-Hansen Carol, Norheim Gunnstein, Abebe Markos, Aseffa Abraham, Tønjum Tone
Department of Microbiology, Oslo University Hospital, PO Box 4950, NO-0424, Oslo, Nydalen, Norway.
Faculty of Medicine, University of Oslo, PO Box 1171, Blindern, 0318, Oslo, Norway.
BMC Evol Biol. 2016 Jun 30;16(1):146. doi: 10.1186/s12862-016-0715-z.
A deeply rooted phylogenetic lineage of Mycobacterium tuberculosis (M. tuberculosis) termed lineage 7 was discovered in Ethiopia. Whole genome sequencing of 30 lineage 7 strains from patients in Ethiopia was performed. Intra-lineage genome variation was defined and unique characteristics identified with a focus on genes involved in DNA repair, recombination and replication (3R genes).
More than 800 mutations specific to M. tuberculosis lineage 7 strains were identified. The proportion of non-synonymous single nucleotide polymorphisms (nsSNPs) in 3R genes was higher after the recent expansion of M. tuberculosis lineage 7 strain started. The proportion of nsSNPs in genes involved in inorganic ion transport and metabolism was significantly higher before the expansion began. A total of 22346 bp deletions were observed. Lineage 7 strains also exhibited a high number of mutations in genes involved in carbohydrate transport and metabolism, transcription, energy production and conversion.
We have identified unique genomic signatures of the lineage 7 strains. The high frequency of nsSNP in 3R genes after the phylogenetic expansion may have contributed to recent variability and adaptation. The abundance of mutations in genes involved in inorganic ion transport and metabolism before the expansion period may indicate an adaptive response of lineage 7 strains to enable survival, potentially under environmental stress exposure. As lineage 7 strains originally were phylogenetically deeply rooted, this may indicate fundamental adaptive genomic pathways affecting the fitness of M. tuberculosis as a species.
在埃塞俄比亚发现了一种结核分枝杆菌（M. tuberculosis）的深度进化分支，称为分支7。对来自埃塞俄比亚患者的30株分支7菌株进行了全基因组测序。定义了分支内基因组变异，并鉴定了独特特征，重点关注参与DNA修复、重组和复制的基因（3R基因）。
鉴定出800多个结核分枝杆菌分支7菌株特有的突变。在结核分枝杆菌分支7菌株最近开始扩张后，3R基因中非同义单核苷酸多态性（nsSNP）的比例更高。在扩张开始前，参与无机离子转运和代谢的基因中nsSNP的比例显著更高。共观察到22346bp的缺失。分支7菌株在参与碳水化合物转运和代谢、转录、能量产生和转换的基因中也表现出大量突变。
我们已经鉴定出分支7菌株独特的基因组特征。系统发育扩张后3R基因中nsSNP的高频率可能导致了近期的变异性和适应性。扩张期前参与无机离子转运和代谢的基因中大量突变可能表明分支7菌株为了生存而产生的适应性反应，可能是在环境压力暴露下。由于分支7菌株最初在系统发育上根深蒂固，这可能表明存在影响结核分枝杆菌作为一个物种适应性的基本适应性基因组途径。
