| Summary: | <br xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions"><strong>Background: </strong>The predominant model for bacterial pandemics is the emergence of a virulent variant that diversifies as it spreads in human populations. We investigated a 40-year meningococcal disease pandemic caused by the hyper-invasive ET-5/ST-32 complex.</br><br xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions"><strong>Methods: </strong>A global collection of Neisseria meningitidis isolates dating from 1969 to 2008 was whole genome sequenced (WGS) and analysed using a gene-by-gene approach at http://pubmlst.org/neisseria.</br><br xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions"><strong>Findings: </strong>Analysis of WGS data identified a ‘Lineage 5 pan genome’ of 1940 genes, 1752 (92%) of which were present in all isolates (Lineage 5 ‘core genome’). Genetic diversity, which was mostly generated by horizontal gene transfer, was unevenly distributed in the genome; however, genealogical analysis of diverse and conserved core genes, accessory genes, and antigen encoding genes, robustly identified a star phylogeny with a number of sub-lineages. Most European and American isolates belonged to one of two closely related sub-lineages, which had diversified before the identification of the pandemic in the 1970s. A third, genetically more diverse sub-lineage, was associated with Asian isolates. Several isolates had acquired DNA from the related gonococcus.</br><br xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions"><strong>Interpretation: </strong>These data were inconsistent with a single point of origin followed by pandemic spread, rather suggesting that the sub-lineages had diversified and spread by asymptomatic transmission, with multiple distinct strains causing localised hyperendemic outbreaks.</br>
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