Pangenome-Wide Association Study in the Family Reveals Key Evolutionary Aspects of Their Relationship with Their Hosts.

The are a family of obligate intracellular bacteria known for their unique biphasic developmental cycle. are associated with various host organisms, including humans, and have been proposed as emerging pathogens. Genomic studies have significantly enhanced our understanding of biology, host adaptation, and evolutionary processes. In this study, we conducted a complete pangenome association analysis (pan-GWAS) using 101 genomes from the family to identify differentially represented genes in and , revealing their distinct evolutionary strategies for interacting with eukaryotic hosts. Our analysis identified 289 genes with differential abundance between the two clades: 129 showed a strong association with and 160 with . Most genes in were related to the type III secretion system, while genes corresponded to various functional categories, including translation, replication, transport, and metabolism. These findings suggest that has developed a high dependence on mammalian cells for replication, facilitated by a complex T3SS for intracellular manipulation. In contrast, the metabolic and functional diversity in allows it to colonize a broad range of hosts, such as birds, reptiles, amphibians, and mammals, making it a less specialized clade.