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Duplications drive diversity in Bordetella pertussis on an underestimated scale

Jonathan S. Abrahams, Michael R. Weigand, Natalie Ring, Iain MacArthur, Scott Peng, Margaret M. Williams, Barrett Bready, Anthony P. Catalano, Jennifer R. Davis, Michael D. Kaiser, John S. Oliver, Jay M. Sage, Stefan Bagby, M. Lucia Tondella, Andrew R. Gorringe, Andrew Preston
doi: https://doi.org/10.1101/2020.02.06.937284
Jonathan S. Abrahams
1Department of Biology and Biochemistry and Milner Centre for Evolution, University of Bath, Bath, U.K
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Michael R. Weigand
2Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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Natalie Ring
1Department of Biology and Biochemistry and Milner Centre for Evolution, University of Bath, Bath, U.K
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Iain MacArthur
1Department of Biology and Biochemistry and Milner Centre for Evolution, University of Bath, Bath, U.K
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Scott Peng
2Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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Margaret M. Williams
2Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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Barrett Bready
3Nabsys 2.0, Providence, RI 02809
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Anthony P. Catalano
3Nabsys 2.0, Providence, RI 02809
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Jennifer R. Davis
3Nabsys 2.0, Providence, RI 02809
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Michael D. Kaiser
3Nabsys 2.0, Providence, RI 02809
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John S. Oliver
3Nabsys 2.0, Providence, RI 02809
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Jay M. Sage
3Nabsys 2.0, Providence, RI 02809
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Stefan Bagby
1Department of Biology and Biochemistry and Milner Centre for Evolution, University of Bath, Bath, U.K
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M. Lucia Tondella
2Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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Andrew R. Gorringe
4Public Health England, Porton Down, Salisbury, UK
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Andrew Preston
1Department of Biology and Biochemistry and Milner Centre for Evolution, University of Bath, Bath, U.K
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  • For correspondence: a.preston@bath.ac.uk
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Abstract

Bacterial genetic diversity is often described using solely base pair changes despite a wide variety of other mutation types likely being major contributors. Tandem duplications of genomic loci are thought to be widespread among bacteria but due to their often intractable size and instability, comprehensive studies of the range and genome dynamics of these mutations are rare. We define a methodology to investigate duplications 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 duplications to occur. Analysis of genome sequence data for 2430 B. pertussis isolates identified 272 putative duplications, of which 94% were located at 11 hotspot loci. We demonstrate limited phylogenetic connection for the occurrence of duplications, suggesting unstable and sporadic characteristics. Genome instability was further described in-vitro using long read sequencing via the Nanopore platform. Clonally derived laboratory cultures produced heterogenous populations containing multiple structural variants. Short read data was used to predict 272 duplications, whilst long reads generated on the Nanopore platform enabled the in-depth study of the genome dynamics of tandem duplications in B. pertussis. Our work reveals the unrecognised and dynamic genetic diversity of B. pertussis and, as the complexity of the B. pertussis genome is not unique, highlights the need for a holistic and fundamental understanding of bacterial genetics.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 07, 2020.
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Duplications drive diversity in Bordetella pertussis on an underestimated scale
Jonathan S. Abrahams, Michael R. Weigand, Natalie Ring, Iain MacArthur, Scott Peng, Margaret M. Williams, Barrett Bready, Anthony P. Catalano, Jennifer R. Davis, Michael D. Kaiser, John S. Oliver, Jay M. Sage, Stefan Bagby, M. Lucia Tondella, Andrew R. Gorringe, Andrew Preston
bioRxiv 2020.02.06.937284; doi: https://doi.org/10.1101/2020.02.06.937284
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Duplications drive diversity in Bordetella pertussis on an underestimated scale
Jonathan S. Abrahams, Michael R. Weigand, Natalie Ring, Iain MacArthur, Scott Peng, Margaret M. Williams, Barrett Bready, Anthony P. Catalano, Jennifer R. Davis, Michael D. Kaiser, John S. Oliver, Jay M. Sage, Stefan Bagby, M. Lucia Tondella, Andrew R. Gorringe, Andrew Preston
bioRxiv 2020.02.06.937284; doi: https://doi.org/10.1101/2020.02.06.937284

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