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

Wu, B.; Zhu, W.; Wang, Y.; Wang, Q.; Zhou, L.; Liu, Z. W.; Bi, L.; Barun, M.; Kreiswirth, B. N.; Chen, L.; Chen, S.; Wang, X.; Wang, W.

doi:10.1101/2020.11.07.372573

bioRxiv · 10.1101/2020.11.07.372573

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

Wu, B.·Zhu, W.·Wang, Y.·Wang, Q.·Zhou, L.·Liu, Z. W.·Bi, L.·Barun, M.·Kreiswirth, B. N.·Chen, L.·Chen, S.·Wang, X.·Wang, W.

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Abstract

The causative agent of tuberculosis (TB) comprises seven human-adapted lineages. Human movements and host genetics are crucial to TB dissemination. We analyzed whole-genome sequencing data for a countrywide collection of 1154 isolates and a provincial collection of 1296 isolates, constructed the best-scoring maximum likelihood phylogenetic tree, conducted Bayesian evolutionary analysis to compute the most recent common ancestors of lineages 2 and 4, and assessed the antigenic diversity in human T cell epitopes by calculating pairwise dN/dS ratios. Of the 1296 Zhejiang isolates, 964 (74.38%) belonged to lineage 2 and 332 (25.62%) belonged to lineage 4. L2.2 is the most ancient sub-lineage in Zhejiang, first appearing approximately 6897 years ago (95% 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 revealed that the epitope and non-epitope regions of lineage 2 strains were significantly (P<0.001) more conserved than those of lineage 4. An increase in the frequency of lineage 4 may reflect its successful transmission over the last 20 years. The recent common ancestors and transmission routes of the sub-lineages are related to the entry of humans into China and Zhejiang Province.

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Wu, B., Zhu, W., Wang, Y., Wang, Q., Zhou, L., Liu, Z. W., Bi, L., Barun, M., Kreiswirth, B. N., Chen, L., Chen, S., Wang, X., Wang, W.. 2020-11-08. Genetic composition and evolution of the prevalent Mycobacterium tuberculosis lineages 2 and 4 in the Chinese and Zhejiang Province populations. https://doi.org/10.1101/2020.11.07.372573

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