Transmission dynamics and phylogeography of Mycobacterium tuberculosis in China based on whole-genome phylogenetic analysis

•The lineage-specific transmission and migration of Mycobacterium tuberculosis in China were revealed.•Lineage 2 is the most prevalent lineage, comprising the major sublineage 2.2.1.•L2.2.1 is highly transmissible and displays frequent cross-regional spread.•Developed regions with high internal migration levels promote tuberculosis transmission. This study aimed to describe the lineage-specific transmissibility and epidemiological migration of Mycobacterium tuberculosis in China. We curated a large set of whole-genome sequences from 3204 M. tuberculosis isolates, including thousands of newly sequenced genomes, and applied a series of metrics to compare the transmissibility of M. tuberculosis strains between lineages and sublineages. The countrywide transmission patterns of major lineages were explored. We found that lineage 2 (L2) was the most prevalent lineage in China (85.7%), with the major sublineage 2.2.1 (80.9%), followed by lineage 4 (L4) (13.8%), which comprises major sublineages 4.2 (1.5%), 4.4 (6.2%) and 4.5 (5.8%). We showed evidence for frequent cross-regional spread and large cluster formation of L2.2.1 strains, whereas L4 strains were relatively geographically restricted in China. Next, we applied a series of genomic indices to evaluate M. tuberculosis strain transmissibility and uncovered higher transmissibility of L2.2.1 compared with the L2.2.2 and L4 sublineages. Phylogeographic analysis showed that southern, eastern, and northern China were highly connected regions for countrywide L2.2.1 strain spread. The present study provides insights into the different transmission and migration patterns of the major M. tuberculosis lineages in China and highlights that transmissible L2.2.1 is a threat to tuberculosis control.