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Mutational spectra are associated with bacterial niche

Published version
Peer-reviewed

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Authors

Weimann, Aaron 
Tonkin-Hill, Gerry 
Pandurangan, Arun Prasad 
Matuszewska, Marta 

Abstract

jats:titleAbstract</jats:title>jats:pAs observed in cancers, individual mutagens and defects in DNA repair create distinctive mutational signatures that combine to form context-specific spectra within cells. We reasoned that similar processes must occur in bacterial lineages, potentially allowing decomposition analysis to detect both disruption of DNA repair processes and exposure to niche-specific mutagens. Here we reconstruct mutational spectra for 84 clades from 31 diverse bacterial species and find distinct mutational patterns. We extract signatures driven by specific DNA repair defects using hypermutator lineages, and further deconvolute the spectra into multiple signatures operating within different clades. We show that these signatures are explained by both bacterial phylogeny and replication niche. By comparing mutational spectra of clades from different environmental and biological locations, we identify niche-associated mutational signatures, and then employ these signatures to infer the predominant replication niches for several clades where this was previously obscure. Our results show that mutational spectra may be associated with sites of bacterial replication when mutagen exposures differ, and can be used in these cases to infer transmission routes for established and emergent human bacterial pathogens.</jats:p>

Description

Acknowledgements: We would like to thank all researchers who helped to obtain published datasets used in this study, including Uzma Basit Khan, Christopher Beaudoin, Sophie Belman, Stephen Bentley, Sebastian Bruchmann, Jessica Calland, Claire Chewapreecha, Jukka Corander, Dorota Jamrozy, Anna Kaarina Pöntinen, Noémie Lefrancq, Stephanie Lo, Neil MacAlasdair, Samuel Sheppard, Andries van Tonder and Lucy Weinert. Funding for this work was provided by The Wellcome Trust through Investigator awards 107032/Z/15/Z (R.A.F., C.R., A.W.) and 200814/Z/16/Z (T.L.B., A.P.P.), Fondation Botnar (Programme grant 6063; R.A.F., J.P., T.L.B., C.R., A.W.) and the UK CF Trust (Innovation Hub Award 001; Strategic Research Centre SRC010; C.R., A.W., T.L.B., R.A.F., J.P.).

Keywords

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723

Volume Title

14

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (Wellcome) (107032/Z/15/Z, 200814/Z/16/Z)
Fondation Botnar (Programme grant 6063)
Cystic Fibrosis Trust (CF) (Innovation Hub Award 001, Strategic Research Centre SRC010)