A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome

Poonam Chitale, Alexander D. Lemenze, Emily C. Fogarty, Avi Shah, Courtney Grady, Aubrey R. Odom-Mabey, W. Evan Johnson, Jason H. Yang, A. Murat Eren, Roland Brosch, Pradeep Kumar and David Alland ()
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Poonam Chitale: Rutgers University – New Jersey Medical School
Alexander D. Lemenze: Rutgers—The State University of New Jersey
Emily C. Fogarty: University of Chicago
Avi Shah: Rutgers University – New Jersey Medical School
Courtney Grady: Rutgers University – New Jersey Medical School
Aubrey R. Odom-Mabey: Boston University School of Medicine and Bioinformatics Program, Boston University
W. Evan Johnson: Rutgers University – New Jersey Medical School
Jason H. Yang: Rutgers University – New Jersey Medical School
A. Murat Eren: Helmholtz Institute for Functional Marine Biodiversity (HIFMB)
Roland Brosch: Université Paris Cité, Unit for Integrated Mycobacterial Pathogenomics
Pradeep Kumar: Rutgers University – New Jersey Medical School
David Alland: Rutgers University – New Jersey Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract H37Rv is the most widely used Mycobacterium tuberculosis strain, and its genome is globally used as the M. tuberculosis reference sequence. Here, we present Bact-Builder, a pipeline that uses consensus building to generate complete and accurate bacterial genome sequences and apply it to three independently cultured and sequenced H37Rv aliquots of a single laboratory stock. Two of the 4,417,942 base-pair long H37Rv assemblies are 100% identical, with the third differing by a single nucleotide. Compared to the existing H37Rv reference, the new sequence contains ~6.4 kb additional base pairs, encoding ten new regions that include insertions in PE/PPE genes and new paralogs of esxN and esxJ, which are differentially expressed compared to the reference genes. New sequencing and de novo assemblies with Bact-Builder confirm that all 10 regions, plus small additional polymorphisms, are also present in the commonly used H37Rv strains NR123, TMC102, and H37Rv1998. Thus, Bact-Builder shows promise as an improved method to perform accurate and reproducible de novo assemblies of bacterial genomes, and our work provides important updates to the primary M. tuberculosis reference genome.

Date: 2022
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DOI: 10.1038/s41467-022-34853-x

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