Intraspecies characterization of bacteria via evolutionary modeling of protein domains

Abstract The characterization of bacterial communities that colonize a biological ecosystem is crucial for both the monitoring of infections and epidemics and the study of the health of organisms that live in a symbiotic relationship with bacteria. This is the case of humans, for which the connection between health and microbiota is now well established. To this aim, a commonly used technique is the sequencing of the 16S rRNA gene DNA derived from the sample of interest. This is usually followed by the pairwise comparison of the measured sequences, and by their association to human-made labels through taxonomic classification. Here, we propose a new approach to define the phylogenetic distance between bacteria based on protein domains: the evolving units of proteins. We analyse 3368 bacterial genomes. We derive their protein domain composition and, using an ecological modeling approach in which protein domains are considered as species that populate the genome, we derive a new measurement of phylogenetic distance. We show that our model-based distance is capable of detecting differences between bacteria in cases in which the 16S rRNA-based method fails, providing a possibly complementary approach particularly promising for the analysis of bacterial populations measured by shotgun sequencing.