Deep evolutionary history of bacterial pathogens (360G-Wellcome-202792_Z_16_Z)

How old are bacterial pathogens, and what evolutionary steps have they undergone? Comparative genomics can accurately resolve recent demography and genealogy of bacterial pathogens. Some historical pathogenic lineages have also been reconstructed by taking advantage of ancient genomes (aDNA), including the causes of plague, cholera, tuberculosis and leprosy. Although ground-breaking, these lineages were relatively easy to analyse using conventional tools due to limited genetic diversity and little recombination, and prior studies on existing genomic diversity. Generating a historical framework for most bacterial pathogens that currently threaten human health, and our food supply, is much more challenging because historical records do not provide unambiguous bacterial identification. Furthermore, the long-term population structure and genealogies of most bacteria are not well defined due to high levels of genetic diversity and frequent recombination, including Salmonella enterica. We will reconstruct the long-term evolutionary history of bacterial pathogens using both metagenomic data from ancient samples and population genetic data from present-day bacteria. We will use the latest developments in aDNA sequencing, develop new bioinformatic approaches for metagenomic analyses, and create a big-data overview of modern genetic diversity. This strategy will be implemented for S. enterica, and then applied to other pathogens.