Ancient DNA sheds light on evolution of relapsing fever bacteria

Researchers at the Francis Crick Institute and UCL have analyzed ancient DNA from Borrelia recurrentis, a type of bacteria that causes relapsing fever, pinpointing when it evolved to spread through lice rather than ticks, and how it gained and lost genes in the process.

This transition may have coincided with changes in human lifestyles, like living closer together and the beginning of the wool trade.

Borrelia recurrentis bacteria cause relapsing fever, an illness with many recurring episodes of fever, which is typically found today in areas with poor sanitation or overcrowding, such as refugee camps. It is a distant cousin of the bacteria that today cause Lyme disease.

Historical records in Britain have referred to periods of a 'sweating sickness' or 'epidemic fever' which may have been caused by B. recurrentis, but limited data means the likely cause of these outbreaks remains unknown.

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. Until now it was unknown when B. recurrentis made the jump from ticks to lice and what impact this had on disease transmission and severity in humans. 

In research published today in Science, the scientists sequenced the whole genome from four samples of B. recurrentis. Ranging from 2,300 to 600 years ago, their samples include the oldest B. recurrentis genome to date. These ancient samples were obtained from the skeletons of people who were infected hundreds of years ago. The DNA is a shadow of the bacteria that once circulated in their blood and has been captured in bones and teeth.

The individuals' teeth contained traces of B. recurrentis DNA. Two samples had relatively high amounts of the pathogen, suggesting these individuals may have died from a severe, acute infection, or that the DNA was particularly well preserved.

Becoming adapted to the human louse

The researchers looked at 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.

They compared the B. recurrentis genomes with B. duttonii, finding that much of the genome was lost during the tick-to-louse transition but that 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 neighbouring bacteria, suggesting B. recurrentis had specialised to survive within the human louse.

The perfect conditions

Based on these ancient and modern genomes, the divergence from the bacteria's tick-borne ancestor happened during the transition from the Neolithic period to the Early Bronze Age. This was a time of change in human lifestyles, as people began to domesticate animals and live in more dense settlements. This may have helped B. recurrentis spread from person to person more easily.

The researchers also raise the possibility that the development of sheep farming for wool at this time may have given an advantage to louse-borne pathogens, as wool has better conditions for lice to lay eggs.

They conclude that the evolution of B. recurrentis highlights that a combination of genetic and environmental changes can help pathogens spread and infect populations more easily.

Louse-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. Although there's a trend towards genome decay as it adapted to the human louse vector, we've shown that the evolution of B. recurrentis was dynamic until about 1,000 years ago, when it looks similar to present-day genomes."

Pooja Swali, Research Fellow at UCL, former Crick PhD student and first author

Pontus Skoglund, Group Leader of the Ancient Genomics Laboratory at the Crick, and co-senior author, said: "Ancient DNA can enhance our understanding of significant but understudied diseases like relapsing fever. Understanding how bacteria such as ​​B. recurrentis​ became more ​severe​​ in the past may help us understand how diseases could change in the future. The time points we've identified suggest that ​​changes in human societies​ such as new clothing material or living in larger groups​ may have allowed B. recurrentis to jump vectors and become more lethal, an example of how pathogens and humans have co-evolved." 

Lucy van Dorp, Group Leader at UCL, and co-senior author, said: "Genetic analysis of these infections in ancient humans has allowed us to directly track how B. recurrentis has juggled loss and gain of genes during its evolution. Its ability to spread and cause disease appears to be context-dependent, with ancient DNA allowing us to speculate on the important role of past human interactions and behaviour in creating conditions conducive to disease spread. More samples will help us to narrow down the events which led to this tick-to-louse transition and the genetic mechanisms which have helped the bacteria thrive using either vector."