中国结核分枝杆菌谱系2群体遗传学研究

目的 研究中国流行的结核分枝杆菌谱系2的遗传结构和地理分布,为制定结核病防控策略提供科学依据。方法 采用标准15位点分枝杆菌散在重复单位-数目可变串联重复序列（variable number tandem repeats,VNTR）技术对来自全国31省市抽样调查的2 900株结核分枝杆菌谱系2进行基因分型。基于上述菌株15-VNTR数据,采用贝叶斯聚类法STRUCTURE进行群体遗传结构分析;构建邻接（Neighbor-Joining,NJ）树和最小生成树（Minimum Spanning Trees,MST）进行群体遗传分化分析。运用主成分分析（principal component analysis,PCA）验证。结果 STRUCTURE分析显示谱系2可分为4个亚群;MST拓扑结构提示亚群2位于奠基者位置,较古老;其他亚群（亚群1、3、4）位于分枝位置,较现代。亚群2主要分布于西南地区和东北三省;亚群1,3,4主要分布于我国东中部地区,推测由于人口的迁徙,造成菌株间遗传距离较近,由东北地区向东中部地区传播。主成分分析显示4群菌株分化不明显。结论 结核分枝杆菌谱系2可分为4个亚群,各亚群的遗传地理分布不同,上述结果对制定我国精准结核病防控策略将产生积极影响。

Population genetics study of Mycobacterium tuberculosis lineage 2 in China

Objective Studying the genetic structure and geographic distribution of Mycobacterium tuberculosis lineage 2 circulating in China will provide a scientific basis for formulating tuberculosis prevention and control strategies.Methods The standard 15-site mycobacterial scattered repeat unit-variable number tandem repeats(VNTR)technique was used to genotype 2900 strains of Mycobacterium tuberculosis lineage 2 from a sample survey of 31 provinces and cities across the country.Based on the above-mentioned strain 15-VNTR data,Bayesian clustering method STRUCTURE was used to analyze the population genetic structure;Neighbor-Joining(N-J)trees and Minimum Spanning Trees(MST)were constructed for population genetic differentiation analysis.Principal component analysis(PCA)was used to verify.Results STRUCTURE analysis showed that pedigree 2 could be divided into 4 clades;the MST topology suggested that clade 2 was located at the founder’s position and was older;the other clades(clade 1,3,4)were located at the branch position,which were more modern.Clade 2 is mainly distributed in the southwestern region and the three northeastern provinces;Clade 1,3,and 4 are mainly distributed in the eastern and central regions of my country.It was speculated that due to population migration,the genetic distance between the strains was relatively close,and the strains spread from northeast to central China.Principal component analysis showed that the differentiation of the four strains was not obvious.Conclusion The Mycobacterium tuberculosis lineage 2 can be divided into 4 subgroups,and the genetic geographic distribution of each subgroup is different.The above results will have a positive impact on the formulation of precision tuberculosis prevention and control strategies in my country.