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Lyme Disease History, Future Explored With North American Borrelia Genome Set

NEW YORK (GenomeWeb) – A new genomic analysis points to a long and complex evolutionary history for the Lyme disease-causing Borrelia burgdorferi sensu stricto bacteria in North America.

Investigators from Yale University, Johns Hopkins University, and Columbia University used hybrid capture and sequencing to characterize nearly 150 B. burgdorferi s.s. representatives from infected Ixodes scapularis nymph ticks collected in the US and Canada over almost three decades. Their analyses of these and other B. burgdorferi genomes suggested that the Lyme disease-causing bacteria has a history of widespread migration and mixing in North America, along with ancient diversity stretching back tens of thousands of years.

"The patterns of migration uncovered here suggest continued spread of diverse B. burgdorferi not only from the northeast across the reset of North America but also in several other directions, with gene flow occurring not only locally but also on a continental scale," corresponding author Katharine Walter, a researcher of microbial disease epidemiology at Yale University, and her co-authors wrote in Nature Ecology and Evolution. "This finding has important epidemiological consequences as it suggests that wide regions with established tick and vertebrate host populations are potential sites of B. burgdorferi invasion and future Lyme disease."

Using Illumina HiSeq 2500 instruments, collaborators at the Yale Center for Genomic Analysis did genome sequencing on 146 B. burgdorferi s.s. isolates collected with custom hybridization capture arrays from infected ticks from the Northeast and Midwest US and from southern Canada between 1984 and 2013.

Along with the bacterial genome sequences, the team was able to tap into bits of co-occurring sequences to learn more about tick vectors for B. burgdorferi and the other microbes they carry.

"Our genomic collection allowed us to simultaneously study DNA from B. burgdorferi, the tick vector, and a co-vectored parasite, Babesia microti," the authors explained.

When they analyzed the new genomes alongside the B. burgdorferi reference sequence and other genomes published previously, the researchers uncovered nearly 19 million SNPs spanning the microbe's linear chromosome and another 1,034 SNPs peppered across two of it plasmids. From there, they used phylogenetic analyses, substitution patterns, and other features to explore population structure and retrace the history of B. burgdorferi in North America.

Although Lyme disease has only been documented on the continent since the 1970s, they estimated that the B. burgdorferi isolates considered shared a common ancestor stretching back some 60,000 years, with a population boost occurring roughly 20,000 years ago.

"Our finding of ancient B. burgdorferi diversification suggests that the recent Lyme disease epidemic does not reflect evolutionary processes but rather was driven by the ecological change in North America beginning in the colonial period [approximately] 700 years ago," the authors proposed. "Deforestation and intensive hunting during the colonial period followed by population explosion of white-tailed deer and climate change in the past century probably enable dramatic range expansion of Ixodes spp. ticks."

The team did not find evidence for co-evolution between B. burgdorferi and the ticks that transmit the bug, though the Lyme disease culprit appears to have been capable of widespread movement and mixing.

"The complex phylogenetic structure of B. burgdorferi together with the migration rate analyses suggest previously undocumented levels of gene flow across North America," the authors wrote. "As Ixodes ticks move little, B. burgdorferi spreads through the movement of its vertebrate hosts, small mammals and birds."