Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese

Significance Mycobacterium tuberculosis Beijing family is a group of globally emerging bacterial strains that are responsible for more than a quarter of the global tuberculosis epidemic. Here, we combine whole-genome sequencing and large-scale genotyping to map the temporal and spatial changes of the genetic diversity within this strain family. We reveal a southern East Asia origin and a parallel evolution of this bacterial genotype with modern humans in East Asia during the last 30,000 years. The recently globally emerged Beijing strains mainly belong to a hypervirulent subtype that most likely has initially been selected for adaption to increased population densities during the agricultural transition in northern China. The Beijing family is the most successful genotype of Mycobacterium tuberculosis and responsible for more than a quarter of the global tuberculosis epidemic. As the predominant genotype in East Asia, the Beijing family has been emerging in various areas of the world and is often associated with disease outbreaks and antibiotic resistance. Revealing the origin and historical dissemination of this strain family is important for understanding its current global success. Here we characterized the global diversity of this family based on whole-genome sequences of 358 Beijing strains. We show that the Beijing strains endemic in East Asia are genetically diverse, whereas the globally emerging strains mostly belong to a more homogenous subtype known as “modern” Beijing. Phylogeographic and coalescent analyses indicate that the Beijing family most likely emerged around 30,000 y ago in southern East Asia, and accompanied the early colonization by modern humans in this area. By combining the genomic data and genotyping result of 1,793 strains from across China, we found the “modern” Beijing sublineage experienced massive expansions in northern China during the Neolithic era and subsequently spread to other regions following the migration of Han Chinese. Our results support a parallel evolution of the Beijing family and modern humans in East Asia. The dominance of the “modern” Beijing sublineage in East Asia and its recent global emergence are most likely driven by its hypervirulence, which might reflect adaption to increased human population densities linked to the agricultural transition in northern China.