1887

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Volume 8, Issue 6

A critical evaluation of pangenomics, with reference to its utility in outbreak investigation Open Access

Abstract

The increased accessibility of next generation sequencing has allowed enough genomes from a given bacterial species to be sequenced to describe the distribution of genes in the pangenome, without limiting analyses to genes present in reference strains. Although some taxa have thousands of whole genome sequences available on public databases, most genomes were sequenced with short read technology, resulting in incomplete assemblies. Studying pangenomes could lead to important insights into adaptation, pathogenicity, or molecular epidemiology, however given the known information loss inherent in analyzing contig-level assemblies, these inferences may be biased or inaccurate. In this study we describe the pangenome of a clonally evolving pathogen, , and examine the utility of gene content variation in outbreak investigation. We constructed the pangenome using 1463 assembled genomes. We tested the assumption of strict clonal evolution by studying evidence of recombination in core genes and analyzing the distribution of accessory genes among core monophyletic groups. To determine if gene content variation could be utilized in outbreak investigation, we carefully examined accessory genes detected in a well described outbreak in Minnesota. We found significant errors in accessory gene classification. After accounting for these errors, we show that has a much smaller accessory genome than previously described and provide evidence supporting ongoing clonal evolution and a closed pangenome, with little gene content variation generated over outbreaks. We also identified frameshift mutations in multiple genes, including a mutation in , which has recently been associated with antibiotic tolerance in . A pangenomic approach enables a more comprehensive analysis of genome dynamics than is possible with reference-based approaches; however, without critical evaluation of accessory gene content, inferences of transmission patterns employing these loci could be misguided.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): molecular epidemiology , Mycobacterium tuberculosis complex and pangenomics
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-06-28
2024-04-26
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A critical evaluation of Mycobacterium bovis pangenomics, with reference to its utility in outbreak investigation
M Gen 8, 000839 (2022); https://doi.org/10.1099/mgen.0.000839
/content/journal/mgen/10.1099/mgen.0.000839
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