Evolutionary genomics of Borrelia burgdorferi sensu lato: Findings, hypotheses, and the rise of hybrids

Abstract

Borrelia burgdorferi sensu lato (B. burgdorferi s.l.), the group of bacterial species represented by Lyme Disease pathogens, has one of the most complex and variable genomic architectures among prokaryotes. Showing frequent recombination within and limited gene flow among geographic populations, the B. burgdorferi s.l. genomes provides an excellent window into the processes of bacterial evolution at both within- and between-population levels. Comparative analyses of B. burgdorferi s.l. genomes revealed a highly dynamic plasmid composition but a conservative gene repertoire. Gene duplication and loss as well as sequence variations at loci encoding surface-localized lipoproteins (e.g., the PF54 genes) are strongly associated with adaptive differences between species. There are a great many conserved intergenic spacer sequences that are candidates for cis-regulatory elements and non-coding RNAs. Recombination among coexisting strains occurs at a rate approximately three times the mutation rate. The coexistence of a large number of genomic groups within local B. burgdorferi s.l. populations may be driven by immune-mediated diversifying selection targeting major antigen loci as well as by adaptation to multiple host species. Questions remain regarding the ecological causes (e.g., climate change, host movements, or new adaptations) of the ongoing range expansion of B. burgdorferi s.l. and on the genomic variations associated with its ecological and clinical variability. Anticipating an explosive growth of the number of B. burgdorferi s.l. genomes sampled from both within and among species, we propose genome-based methods to test adaptive mechanisms and to identify molecular bases of phenotypic variations. Genome sequencing is also necessary to monitor the ongoing genetic admixture of previously isolated species and populations in North America and elsewhere.

Whole Genome Sequence and Comparative Genomics of the Novel Lyme Borreliosis Causing Pathogen, Borrelia mayonii

“…mayonii strains belong to the same allele group, termed here OspC type Bmayo1. Phylogenetic analysis of a ~6.5 kbp region of cp26, shown previously to be relatively free from recombination in Bbsl genospecies [22], is shown in Fig 4. The two B .…”

“…Phylogenetic analysis of a ~6.5 kbp region of cp26 from Bbsl genospecies was performed using MEGA6 [36]. Briefly, DNA sequences were aligned using MUSCLE, maximum likelihood trees generated using 4 discrete gamma categories and rooted at the midpoint based on Qiu et al 2014 [22], followed by 1000 bootstrap replicates. Sequences included in the phylogenetic analysis were retrieved from GenBank.…”

“…Because of the similar sizes and highly paralogous nature of Bbsl plasmid sequences, next generation sequencing platforms have often yielded unfinished genome assemblies of Bbsl genospecies [22]. Short read platforms are typically unable to span the large number of repetitive regions present in Borrelia strains which in turn means the origin of the read cannot be precisely determined.…”

Division of the genus Borrelia into two genera (corresponding to Lyme disease and relapsing fever groups) reflects their genetic and phenotypic distinctiveness and will lead to a better understanding of these two groups of microbes (Margos et al. (2016) There is inadequate evidence to support the division of the genus Borrelia. Int. J. Syst. Evol. Microbiol. doi: 10.1099/ijsem.0.001717)

“…Extensive work on these sequence-based characteristic markers on other groups of prokaryotes have shown that these markers possess a high degree of predictive ability to be identified in other group members, for which no sequence information may be available at the time (reviewed in [76,77]). With the more explicit division of the Borreliaceae species into two genus-level groups, attention can be focused on unique genetic and molecular characteristics that differentiate the two groups of microbes [78]; the described characteristics in other groups of bacteria have been found to play important and generally essential roles [79]. For Borreliaceae species, some of the CSIs that distinguish between the RF and LD groups are in proteins, such as the flagellar motor switch protein FliM, chemotaxis proteins CheY and CheW, and cell shape-determining protein MreB [4], that Margos et al [7] write that 'splitting the genus does not provide any assistance as far as clinical evaluation is concerned' and further that '[it] does not help end user communities including in clinical medical practice, public health, or those studying the ecology of the bacteria'.…”

Similarities in murine infection and immune response to Borrelia bissettii and Borrelia burgdorferi sensu stricto

“…One Borrelia species, Borrelia bissettii, is found overlapping the distribution of B. burgdorferi ss in the US and in areas of Europe (Margos et al, 2012). The B. bissettii spirochaete is phylogenetically closely related to the human pathogenic B. burgdorferi ss species (Qiu & Martin, 2014). To date, three studies have demonstrated molecular detection of B. bissettii (Girard et al, 2011;Rudenko et al, 2008Rudenko et al, , 2009 in human clinical samples.…”