Genetic composition and evolution of the prevalent Mycobacterium tuberculosis lineages 2 and 4 in the Chinese and Zhejiang Province populations

Beibei Wu,Lijun Bi,Barry N Kreiswirth,Liang Chen,Mathema Barun,Weibing Wang,Songhua Chen,Xiaomeng Wang,Yue Wang,Qi Wang,Lin Zhou,Zhengwei Liu,Wenlong Zhu

doi:10.1186/s13578-021-00673-7

Abstract

BackgroundThere are seven human-adaptation lineages of Mycobacterium tuberculosis (Mtb). Tuberculosis (TB) dissemination is strongly influenced by human movements and host genetics. The detailed lineage distribution evolution of Mtb in Zhejiang Province is unknown. We aim to determine how different sub-lineages are transmitted and distributed within China and Zhejiang Province.MethodsWe analysed whole-genome sequencing data for a worldwide collection of 1154 isolates and a provincial collection of 1296 isolates, constructed the best-scoring maximum likelihood phylogenetic tree. Bayesian evolutionary analysis was used to calculate the latest common ancestor of lineages 2 and 4. The antigenic diversity of human T cell epitopes was evaluated by calculating the pairwise dN/dS ratios.ResultsOf the Zhejiang isolates, 964 (74.38%) belonged to lineage 2 and 332 (25.62%) belonged to lineage 4. The distributions of the sub-lineages varied across the geographic regions of Zhejiang Province. L2.2 is the most ancient sub-lineage in Zhejiang, first appearing approximately 6897 years ago (95% highest posterior density interval (HDI): 6513–7298). L4.4 is the most modern sub-lineage, first appearing approximately 2217 years ago (95% HDI: 1864–2581). The dN/dS ratios showed that the epitope and non-epitope regions of lineage 2 strains were significantly (P < 0.001) more conserved than those of lineage 4.ConclusionsAn increase in the frequency of lineage 4 may reflect its successful transmission over the last 20 years. The recent common ancestors of the sub-lineages and their transmission routes are relevant to the entry of humans into China and Zhejiang Province. Diversity in T cell epitopes may prevent Mycobacterium tuberculosis from being recognized by the immune system.

Highlights

There are seven human-adaptation lineages of Mycobacterium tuberculosis (Mtb)
We examine the SNPs shared by the predominant lineages in China as a means to explore the common genetic characteristics that have contributed to its wide transmission
Phylogenetic characteristics of the lineage 2 and lineage 4 strains whole-genome sequencing (WGS) data consisted of the data of the 1296 Mtb isolates from Zhejiang Province (Additional file 1: Table S1) and the data of the 1154 previously studied isolates from around the world (Additional file 2: Table S2)

Summary

Introduction

There are seven human-adaptation lineages of Mycobacterium tuberculosis (Mtb). The detailed lineage distribution evolution of Mtb in Zhejiang Province is unknown. We aim to determine how different sub-lineages are transmitted and distributed within China and Zhejiang Province. The causative agent of tuberculosis (TB), Mycobacterium tuberculosis (Mtb), is an obligate pathogen that comprises seven human-adapted lineages [1]. Mtb is one of the most successful human pathogens, having killed an estimated 1 billion people over the last 200 years [2]. Accumulating evidence indicates that human migrations and activities influence the population structure of Mtb [7]. Human-adapted Mtb lineages have shown a strong phylogeographic population structure in which different lineages are associated with distinct geographic regions [8,9,10].

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