Parasite contingency loci and the evolution of host specificity: Simple sequence repeats mediate Bartonella adaptation to a wild rodent host

Parasites can adapt to better exploit their hosts on many timescales, ranging from within a single infection to across serial infections of multiple hosts. However, little is known about how the genomes of parasites in natural communities evolve when they face diverse hosts. We investigated how Bartonella bacteria that circulate in rodent communities in the dunes of the Negev Desert in Israel adapt to different hosts. We propagated 15 Bartonella populations through infections of either a single rodent species (Gerbillus andersoni or Gerbillus pyramidum) or alternating between the two. After 20 rodent passages, strains with de novo mutations outcompeted the ancestor in most lines. Mutations in two mononucleotide simple sequence repeats (SSRs) dominated the evolutionary dynamics and caused frameshifts in the same adhesin gene. These mutations appeared exclusively in populations that encountered G. andersoni, and they improved the ability to exploit this host. Similar SSRs in other genes are conserved and exhibit ON/OFF variation in Bartonella isolates from the Negev Desert dunes. Our results suggest that SSR-based contingency loci are important not only for rapidly and reversibly generating antigenic variation to escape immune responses but may also play a prominent role in the evolution of host specificity. ### Competing Interest Statement The authors have declared no competing interest.