Towards Comprehensive Understanding of Bacterial Genetic Diversity: Large Scale Amplifications in Bordetella pertussis and Mycobacterium tuberculosis.

Jonathan Abrahams, Michael Weigand, Natalie Ring, Iain MacArthur, Joss Etty, Scott Peng, Margaret Williams, Barrett Bready, Anthony Catalano, Jennifer Davis, Michael Kaiser, John Oliver, Jay Sage, Stefan Bagby, M Lucia Tondella, Andrew Gorringe, Andrew Preston

Research output: Contribution to journalArticlepeer-review


Bacterial genetic diversity is often described solely using base-pair changes despite a wide variety of other mutation types likely being major contributors. Tandem duplication/amplifications are thought to be widespread among bacteria but due to their often-intractable size and instability, comprehensive studies of these mutations are rare. We define a methodology to investigate amplifications in bacterial genomes based on read depth of genome sequence data as a proxy for copy number. We demonstrate the approach with Bordetella pertussis, whose insertion sequence element-rich genome provides extensive scope for amplifications to occur. Analysis of data for 2430 B. pertussis isolates identified 272 putative amplifications, of which 94% were located at 11 hotspot loci. We demonstrate limited phylogenetic connection for the occurrence of amplifications, suggesting unstable and sporadic characteristics. Genome instability was further described in vitro using long-read sequencing via the Nanopore platform, which revealed that clonally derived laboratory cultures produced heterogenous populations rapidly. We extended this research to analyse a population of 1000 isolates of another important pathogen, Mycobacterium tuberculosis. We found 590 amplifications in M. tuberculosis, and like B. pertussis, these occurred primarily at hotspots. Genes amplified in B. pertussis include those involved in motility and respiration, whilst in M. tuberuclosis, functions included intracellular growth and regulation of virulence. Using publicly available short-read data we predicted previously unrecognized, large amplifications in B. pertussis and M. tuberculosis. This reveals the unrecognized and dynamic genetic diversity of B. pertussis and M. tuberculosis, highlighting the need for a more holistic understanding of bacterial genetics.

Original languageEnglish
Article number000761
Pages (from-to)1-15
Number of pages15
JournalMicrobial Genomics
Issue number2
Early online date10 Feb 2022
Publication statusE-pub ahead of print - 10 Feb 2022


  • B. pertussis
  • amplifications
  • duplications
  • genetic diversity
  • genome structure

ASJC Scopus subject areas

  • Epidemiology
  • Microbiology
  • Molecular Biology
  • Genetics


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