Introduction
Lyme borreliosis (LB), also termed Lyme disease, is the most common vector-borne disease in the Northern hemisphere (Stanek et al., 2011; Steere, Coburn, & Glickstein, 2004), caused by certain genospecies ofBorrelia bacteria (Kurtenbach et al., 2006; Gabriele Margos, Fingerle, & Reynolds, 2019; Stanek et al., 2011). These spirochete bacteria are maintained naturally in obligatory transmission cycles between tick vectors and specific vertebrate reservoir hosts (Kurtenbach et al., 2006). In North America human LB is predominantly caused byBorrelia burgdorferi sensu stricto (Bb ss) while three additional genospecies act as causative agents across Eurasia (Borrelia afzelii , Borrelia bavariensis , Borrelia garinii ) (Kurtenbach et al., 2006; Gabriele Margos et al., 2019; Stanek et al., 2011). Genomic analyses have already shown a complex ancestral spread of Bb ss across North America (Walter, Carpi, Caccone, & Diuk-Wasser, 2017) which is also observed in specific Eurasian genospecies (Becker et al., 2020; Ana Cláudia Norte et al., 2020). The Eurasian genospecies offer a unique opportunity to understand the geographic expansion of Borrelia spirochetes using comparative genomics. However, no study has integrated genomic data from the different genospecies. In particular, no study at the population-level of Asian B. afzelii has been published to date.
Borrelia genospecies cannot transmit successfully through all tick species (Eisen, 2020; Gabriele Margos et al., 2019) and can only infect specific vertebrate classes (i.e. rodents, passerines, sea-birds, etc.) while being easily cleared by the immune systems of others (Kurtenbach et al., 2006; Kurtenbach, Sewell, Ogden, Randolph, & Nuttall, 1998; Gabriele Margos et al., 2019). Eurasian Borreliagenospecies currently exist in separate transmission cycles vectored predominately by two generalist tick species in Asia (Ixodes persulcatus ) and Europe (Ixodes ricinus ) (Kurtenbach et al., 2006) (Figure 1). This suggests that each genospecies successfully invaded a novel tick vector resulting in the expansion into a new continental transmission cycle. However, how and in which order this expansion occurred is still unknown (Figure 1). For B. bavariensis, an Asian origin was already hypothesized as the Asian population displays a higher genetic diversity compared to the almost clonal European population (Becker et al., 2020; Gatzmann et al., 2015; Gabriele Margos et al., 2019). European B. bavariensis is thought to have undergone a selective bottleneck while colonizing the European tick vector, I. ricinus , resulting in the observed clonal structure (Becker et al., 2020; Gatzmann et al., 2015; Gabriele Margos et al., 2019). Whether or not the other genospecies also underwent this bottleneck has never been studied so far. Both B. afzelii andB. bavariensis utilize rodents as reservoir hosts (Pär Comstedt, Jakobsson, & Bergström, 2011; Kurtenbach et al., 2006; Gabriele Margos et al., 2009) (Figure 1). In comparison, B. garinii is adapted to avian host species (Pär Comstedt et al., 2009, 2011), which includes interconnected terrestrial and marine transmission cycles (Figure 1). This association in B. garinii is thought to allow for migration between the European and Asian populations which is not accessible to rodent adapted genospecies. (Figure 1).
Each of these genospecies has successfully established into multiple transmission cycles and offers an opportunity to study howBorrelia expanded across Eurasia through comparative genomics. Although, no study to date has integrated genomic data from all three Eurasian-distributed genospecies. Here we report the reconstructed evolutionary history of 142 B. afzelii , B. garinii , andB. bavariensis Eurasian isolates based on full genome sequences including the first Japanese B. afzelii genomes sequenced. Our results highlight that these genospecies share an Asian origin with support for migration from an ancestral Asian population vectored byI. persulcatus into a novel European vector, I. ricinus . Post-colonization gene flow appears to be associated with the dispersal range of the respective reservoir host species. Our results provide new information on the ability of three Borrelia genospecies to colonize new environments and how this could relate to the further expansion of human LB.