Evolution and comparative genomics of tick-associated Francisella endosymbionts: insights into metabolic pathways and historical biogeographic patterns

Ticks (Ixodida) are the second most important vectors of infectious diseases in vertebrates, after mosquitoes. They also maintain mutualistic relationships with bacteria, such as endosymbionts that provide essential B vitamins absent in their blood diet. The most studied endosymbionts belong to the genera Coxiella , Midichloria , and Francisella . Francisella includes endosymbionts (FE), pathogens (FP), putative intermediates (FI), and free-living (FL) strains, making them valuable for evolutionary and comparative genomics. In this study, total DNA from six adult female ticks of the genera Hyalomma and Amblyomma was sequenced to obtain new FE genomes. Additionally, two deep metagenomes from public data were assembled, resulting in a dataset of 22 Francisella strains. This dataset was used to reconstruct a phylogenomic framework and compare vitamin biosynthesis and virulence pathways. An MLST-based dense phylogeny was also built to explore biogeographic patterns. The resulting phylogenomic tree shows FE form a monophyletic group derived from FP, possibly due to historical biogeography or recent horizontal transfers. Comparative analyses reveal that FE retain key metabolic pathways while losing nonessential ones, reflecting a selective genome reduction. These results advance our understanding of symbiont evolution in a changing world, revealing molecular adaptations that underpin tick- symbiont relationships and offering genomic insights with potential applications for disease control.