Ancient DNA Reveals Evolution of Fever-causing Bacteria with Ties to Lyme Disease

By Michelle Taylor

Ancient DNA Reveals Evolution of Fever-causing Bacteria with Ties to Lyme Disease

Richard Madgwick (left), Jack Randell (middle) and Jessica Peto (right) in the Bone Idle Chamber of Fishmongers Swallet. Credit: Adelle Bricking

Ancient DNA samples from as long as 2,300 years ago are revealing evolutionary secrets about Borrelia recurrentis, a type of bacteria that causes relapsing fever and is a distant cousin of the bacteria that causes modern Lyme disease.

Only three known species of bacteria, including B. recurrentis, have transitioned from being carried primarily by ticks to lice, changing the potential severity of the disease. It was unknown when B. recurrentis made the jump from ticks to lice and what impact this had on disease transmission and severity -- until now.

In a new study published in Science, researchers from the Francis Crick Institute and University of College London sequenced the whole genome from four samples of B. recurrentis extracted from the teeth, jawbone and skeleton of four infected, deceased people. Ranging from 2,300 to 600 years old, the samples include the oldest B. recurrentis genome to date.

Historical records in Britain have referred to periods of a "sweating sickness" or "epidemic fever," which may have been caused by B. recurrentis. However, data is limited so the specific cause remains unknown, even given the results of this newest study.

For the study, the research team examined differences in the ancient genomes and modern-day B. recurrentis to map how the bacteria has changed over time, finding that the species likely diverged from its nearest tick-borne cousin -- B. duttonii -- about 6,000 to 4,000 years ago.

Comparing the B. recurrentis genomes with B. duttonii, the team discovered that much of the original genome was lost during the tick-to-lice transition. However, new genes were also gained over time. These genetic changes affected the bacteria's ability to hide from the immune system and also share DNA with neighboring bacteria, suggesting B. recurrentis had specialized to survive within the human lice.

"Lice-borne relapsing fever is a neglected disease with limited modern genomes, making it difficult to study its diversity. Adding four ancient B. recurrentis genomes to the mix has allowed us to create an evolutionary time series and shed light on how the genetics of the bacteria have changed over time," said first author of the study Pooja Swali, research fellow at UCL and former Crick PhD student.

Given the observed genomic differences and timeline, the divergence from the B. recurrentis' tick-borne ancestor happened during the transition from the Neolithic period (10000 BCE) to the Early Bronze Age (3300 BCE). Societally, this was a time of immense change in human lifestyles, as people began to domesticate animals and live in more dense settlements. This newfound closeness may have helped B. recurrentis spread from person to person more easily. Even the domestication of animals could have played a role in transmission as sheep farming for wool became prominent around this time -- and wool has favorable conditions for lice to lay eggs.

"Understanding how bacteria such as B. recurrentis became more severe in the past may help us understand how diseases could change in the future," said co-senior author Pontus Skoglund, group leader of the Ancient Genomics Laboratory at the Crick. "The time points we've identified suggest that changes in human societies may have allowed B. recurrentis to jump vectors and become more lethal, an example of how pathogens and humans have co-evolved."

The research team will continue their work with more samples, which they say will help narrow down the events that led to the tick-to-lice transition and the genetic mechanisms that helped the bacteria thrive with each vector.

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