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Negative frequency-dependent selection and asymmetrical transformation stabilise multi-strain bacterial population structures

By Gabrielle L. Harrow, John Lees, William Hanage, Marc Lipsitch, Jukka Corander, Caroline Colijn, Nicholas J Croucher

Posted 06 Jun 2020
bioRxiv DOI: 10.1101/2020.06.05.118836

Streptococcus pneumoniae can be split into multiple strains, each with a characteristic combination of core and accessory genome variation, able to co-circulate and compete within the same hosts. Previous analyses of epidemiological datasets suggested the short-term vaccine-associated dynamics of S. pneumoniae strains may be mediated through multi-locus negative frequency-dependent selection (NFDS), acting to maintain accessory loci at equilibrium frequencies. To test whether this model could explain how such multi-strain populations were generated, it was modified to incorporate recombination. The outputs of simulations featuring symmetrical recombination were compared with genomic data on locus frequencies and distributions between genotypes, pairwise genetic distances and tree shape. These demonstrated NFDS prevented the loss of variation through neutral drift, but generated unstructured populations of diverse isolates. Making recombination asymmetrical, favouring deletion of accessory loci over insertion, alongside multi-locus NFDS significantly improved the fit to genomic data. In a population at equilibrium, structuring into multiple strains was stable due to outbreeding depression, resulting from recombinants with reduced accessory genomes having lower fitness than their parental genotypes. As many bacteria inhibit the integration of insertions into their chromosomes, this combination of asymmetrical recombination and multi-locus NFDS may underlie the co-existence of strains within a single ecological niche. ### Competing Interest Statement M.L. has consulted for Pfizer, Affinivax, and Merck and has received grant support not related to this paper from Pfizer and PATH Vaccine Solutions. W.P.H., M.L., and N.J.C. have consulted for Antigen Discovery Inc. NJC has received an investigator-initiated award from GlaxoSmithKline.

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