Analysis of the Borreliaceae Pangenome Reveals a Conserved Genomic Archictecture Across Phylogenetic Scales

The Family Borreliaceae contains arthropod-borne spirochetes that cause two widespread human diseases, Lyme disease (LD) and relapsing fever (RF). LD is a subacute, progressive illness with variable stage and tissue manifestations. RF is an acute febrile illness with prominent bacteremia that may recur and disseminate, particularly to the nervous system. Clinical heterogeneity is a hallmark of both diseases. While human clinical manifestations are influenced by a wide variety of factors, including immune status and host genetic susceptibility, there is evidence that Borreliaceae microbial factors influence the clinical manifestations of human disease caused by this Family of spirochetes. Despite these associations, the spirochete genes that influence the severity and manifestations of human disease are, for the most part, unknown. Recent work has identified lineage-specific expansions of lipoproteome-rich accessory genome elements in virulent clones of B. burgdorferi. Using publicly available genome assemblies, I show here that all Borreliaceae lineages for which sufficient sequence data is available harbor a similar pattern of strongly structured, lineage-specific expansions in their accessory genome, particularly among lipoproteins, and that this pattern holds across phylogenetic scales including genera, species, and genotypes. The relationships among pangenome elements suggest that infrequent episodes of marked genomic change followed by clonal expansion in geographically and enzootically structured populations may account for the unique lineage structure of Borreliaceae. This analysis informs future genotype-phenotype studies among Borreliaceae and lays a foundation for studies of individual gene function guided by phylogenetic patterns of conservation, diversification, gain, and/or loss.