Ancient DNA Reveals Origins and History of "Sweating Fever" Bacterium

Throughout history, infectious diseases have profoundly affected human populations, yet key questions about their origins and evolutionary patterns remain unanswered.

Borrelia recurrentis (B. recurrentis) is a type of bacteria that can cause louse-born relapsing fever, or LBRF.

Throughout history this bacterium has been linked to major outbreaks: the 6^th century “Yellow Plague”, epidemics in England, Scotland and Ireland during the 19^th century and two pandemics in Africa during the 20^th century. Today, LBRF typically occurs in areas where sanitation is poor and there are issues with overcrowding.

B. recurrentis is one of three known bacteria transmitted by lice that were once transmitted by ticks. When this transition occurred and how it affected the transmission and severity of LBRF has been challenging to study – LBRF is a neglected disease, and accessing modern B. recurrentis genomes is not easy.

This is where ancient DNA analysis – the study of genomes from ancient samples – can offer a helping hand.

Scientists in the Ancient Genomics Laboratory at The Francis Crick Institute in London recently embarked on a study to explore what pathogens might be lurking in the remains of ancient samples across Britain.

Led by Research Fellow and former Crick PhD student Dr. Pooja Swali, they began by screening a wide range of ancient DNA samples and identified four individuals from ancient Britain that had been infected by B. recurrentis. The samples had been originally obtained across archaeological sites including:

• Wetwang Slack, an Iron Age cemetery in East Yorkshire.
• A medieval chapel in Poulton.
• Fishmonger’s Swallet, an Iron Age cave located in South Gloucestershire.
• An Augustinian cemetery in late medieval Canterbury.

Their research, published in Science, provides a new understanding of the origins and history of B. recurrentis. Swali recently joined Technology Networks to talk about the research project, the technologies enabling ancient DNA analysis work and how ancient DNA can cast a spotlight on understudied pathogens.

Molly Coddington (MC): Why did you decide to focus your study on B. recurrentis?

Pooja Swali (PS): We used a metagenomic approach to screen over a thousand archaeological remains from across Britain, spanning the last 5,000 years, in search of pathogens capable of causing systemic infection that may be present in the dental chambers of the teeth.

B. recurrentis was identified in our metagenomic screen in a handful of individuals – it’s a pathogen of particular interest due to its notable evolutionary shift in transmission dynamics from tick to louse.

However, a lack of modern genomes limits our understanding of this process. This challenge prompted us to adopt a pangenome approach, allowing us to explore the diversity among all relapsing fever-causing Borrelia species and gain deeper insight into this transition.

MC: What advancements in next-generation sequencing – or other tools – enabled this research?

PS: The use of shotgun whole-genome sequencing has enabled us to sequence all the DNA present in our samples, allowing the application of a metagenomic approach. As sequencing becomes more affordable and methods continue to improve – such as the adoption of single-stranded library preparation to recover shorter ancient DNA fragments and computational tools to detect authentic pathogens – it allows us to find the “needle in a haystack”.

MC: What would you describe as the most impactful finding from this study?

PS: B. recurrentis (spread by the human body louse) is largely understudied and neglected, yet when left untreated it is associated with high mortality rates. Today, it predominantly affects areas with overcrowding and poor sanitation, such as refugee camps. The limited number of available genomes makes it challenging to understand the diversity of the pathogen’s genome and to gain insights into its evolutionary processes – processes that have resulted in a more virulent form of relapsing fever compared to its tick-borne relatives.

By sequencing four ancient individuals from Britain, we have created an evolutionary time series to investigate the dynamic evolution of B. recurrentis as it shifted from tick- to louse-borne transmission – a transition associated with increased virulence (higher mortality) and genome reduction.

Our findings indicate that this divergence occurred ~5,000 years ago, a period linked to the trade of secondary animal products such as wool, which is particularly well-suited to harboring louse eggs. This study sheds light on which genes may have been crucial for the changing transmission dynamics and how human behavior may have facilitated the pathogen’s specialization to the louse vector.

Importantly, our results show that this specialization and genome reduction was not a straightforward process. By analyzing ancient DNA, we have been able to identify and date some of the genetic changes involved – both those that may have played a role in the shift to louse specialization and those integral to the pathogen’s need to replicate, such as genes involved in plasmid partitioning. Notably, we found that rapid genome reduction had mostly occurred by 2,300 BP, suggesting that by this point it may have already been louse-borne.

Credit: Pooja Swali, adapted from Swali, P. (2025), Science.

MC: What implications do the findings of this study carry?

PS: This study not only highlights the complexity of vector specialization, but also significantly increases the number of high-quality genomes available to address key questions regarding the evolution of this pathogen. Previously, only seven modern isolates from East Africa had been sequenced, underscoring the limited representation of the pathogen’s diversity. Our work, in conjunction with findings from others (Guellil et al. 2018; Sikora et al. 2023^*) and evidence from historical texts, demonstrates that relapsing fever was once widespread across Europe.

By accessing and analyzing these genetically diverse genomes, we are now able to reconstruct the evolutionary history that has led to the emergence of this unique and specialized pathogen.

Crucially, our research demonstrates how ancient DNA can be invaluable in uncovering both the lost diversity of B. recurrentis and its impact on past populations. Importantly, our work shines a spotlight on neglected and understudied pathogens such as B. recurrentis, which continue to pose significant health risks today.

By expanding our understanding of its evolution and historical prevalence, we hope to encourage greater recognition and prioritization of such pathogens that are often neglected.

MC: Do you have plans to expand this research project?

PS: These ancient genomes have highlighted the complex evolution of B. recurrentis, with only four ancient genomes identified from Britain. As technology and methods continue to advance and become more affordable, enabling deeper sequencing of archaeological remains, it is likely that more B. recurrentis genomes will be discovered. Genomes from outside Britain provide a broader perspective on how significant this disease was during the Iron Age and Medieval period. We also hope that our work will encourage further studies on this bacterium, given that it is often overlooked in global health agendas.

Reference: Swali P, Booth T, Tan CCS, et al. Ancient Borrelia genomes document the evolutionary history of louse-borne relapsing fever. Science. 2025.388(6749):eadr2147. doi: 10.1126/science.adr2147

About the interviewee

Dr. Pooja Swali is a research fellow at University College London, where her research focuses on using ancient DNA techniques in the retrieval, detection and analysis of pathogen genomes from historical samples to trace their evolutionary journey across time. Through the combined analysis of ancient and contemporary genomes, her work strives to understand the fundamental evolutionary processes that have influenced the genomes and geographical distribution of these species today.

Credit: Dr. Pooja Swali.

*This article is based on research findings that are yet to be peer-reviewed. Results are therefore regarded as preliminary and should be interpreted as such. Find out about the role of the peer review process in research here. For further information, please contact the cited source.