Using Pan-Genomes to Include Functional Data in Ancient Pathogen Studies

Abstract

Ancient DNA analyses are reliant on reference genomes to authenticate and identify endogenous genomes. While this has lead to many successful studies involving proboscidians, hominids, and ancient pathogens such as Yersinia pestis, our reliance on at most a small number of genomes greatly limits our ability to functionally describe the genome of interest. Further, given the existence of open bacterial genomes and horizontal gene transfers it is likely that reference biases have been incorporated and cited in following studies as representative of past gene diversity. By implementing and standardizing the use of bacterial pan-genomes the effect of these biases are greatly diminished while also revealing the relative capabilities of the target genome compared to the modern diversity. Describing an ancient strain by both its phylogenetic and functional similarities to modern strains allows for a more nuanced analysis of the species evolutionary history. Incongruencies between the phylogeny and genetic function are ripe for deeper analyses and the implications of its findings resonate beyond the characterization of an ancient genome. A pan-genome centric approach to ancient bacterial studies offers significant improvements compared to the current paradigm.