Ancient Borrelia genomes document the evolutionary history of louse-borne relapsing fever

Abstract

Several bacterial pathogens have transitioned from tick-borne to louse-borne transmission, which often involves genome reduction and increasing virulence. However, the timing of such transitions remains unclear. We sequenced four ancient Borrelia recurrentis genomes, the agent of louse-borne relapsing fever, dating from 2300 to 600 years ago. We estimated the divergence from its closest tick-borne relative to 6000 to 4000 years ago, which suggests an emergence coinciding with human lifestyle changes such as the advent of wool-based textiles. Pan-genome analysis indicated that much of the evolution characteristic of B. recurrentis had occurred by ~2300 years ago, though further gene turnover, particularly in plasmid partitioning, persisted until ~1000 years ago. Our findings provide a direct genomic chronology of the evolution of this specialized vector-borne pathogen.

Figure 1. Overview of ancient genomes.

A. Geographic location of the four ancient B. recurrentis genomes sequenced in this study together with OSL9 previously published by Guellil and colleagues(18). B. Circos plot with the coverage of ancient genomes across the B. recurrentis chromosome and plasmids when aligned to the B. recurrentis A1 reference genome (GCF_000019705.1). A window size of 100bp for the chromosome and 10bp for the plasmids was used to provide the normalised coverage per window plotted. To allow for visualisation, the coverage for each genome was scaled by the maximum coverage per genome (C10416 Wetwang Slack, 70; C13361 Fishmonger’s, 20; C11907 Canterbury, 10; C10976 Poulton, 170; OSL9, 40).

Figure 2. Temporal evolution of Borrelia recurrentis.

A. Bayesian tip-calibrated maximum clade credibility time tree from Beast2, providing the best supported model following path-sampling. The 95% highest posterior density is indicated with purple boxes and within brackets. The placement of Fishmonger’s is indicative following a relaxed tip-calibration analysis. Ancient samples are highlighted by coloured tips. Key gene acquisition and loss events described in the text are highlighted at the relevant phylogenetic nodes. B. Timeline providing the estimated age and X-fold coverage (on a log10-scale) of B. recurrentis observations recovered from ancient DNA in this and other studies.

Figure 3. Gene losses/gains across variable major proteins (vmp), B. duttonii Ly and B. recurrentis A1 plasmids.

Ancient and modern genomes were aligned to single reference B. recurrentis (green) or B. duttonii (orange) (23). Regions of interest highlighted in the text are outlined with a black box. Cladogram provides the relationship between different genomes based on a SNP phylogeny. A) Normalised breadth of coverage across the variable major proteins on the B. recurrentis A1 chromosome and plasmids (pl) (Table S8), using BEDTools v2.29.2. Coordinates of the vmp genes and whether they are classified as genes (yellow) or pseudogenes (purple) were provided in Guellil et al. (18) using previously annotated genomes from the NCBI database. B) Breadth of coverage for B. duttonii Ly plasmids using SAMTools v1.3.1 with a mapping quality of Q1. C) Breadth of coverage for B. recurrentis A1 plasmids using SAMTools v1.3.1 with a mapping quality of Q1.