Ancient DNA Helps Us Understand Pathogens of the Past

Herpes simplex virus, the microbe that causes pesky cold sores, has been around for centuries. More than 2,500 years ago, the ancient Greek philosopher first used the word “herpes,” a term derived from the ancient Greek word meaning “to creep” or “crawl,” to describe the painful and easily spread blisters. Herpes is difficult to cure because the virus can hide away in a person’s nerve cells for a long time without causing any symptoms. Environmental and physiological triggers can cause the virus to reactivate and infect cells. The fact that humans have learned to simply coexist with the virus raises an interesting question – just how old is herpesvirus?

A team of researchers recently isolated and sequenced the genetic material of ancient herpesvirus from the teeth of humans who lived during the Bronze age, which suggests that virus existed as early as 5,000 years ago. Changes in cultural practices, such as the emergence of romantic kissing, contributed to the explosion of herpesvirus infections at the time. This study is just one of many examples of how paleomicrobiology, the study of microbes in ancient remains, provides surprising insights into the origins and evolution of infectious diseases.

Although the world is now facing the new coronavirus disease 2019 (COVID-19) pandemic, major disease outbreaks have wreaked havoc on humans for thousands of years. Infectious diseases such as black plague, cholera and flu wiped out entire communities, leaving an indelible mark on human history. In both the past and present, the emergence of infectious diseases has also been a driving force behind advances in medicine and public health. Therefore, studying the evolutionary history of human pathogens can shape global surveillance efforts to better protect human health and wellbeing.

Studying ancient pathogens has proven to be difficult for several reasons. However, the biggest obstacle is finding enough intact microbial genetic material, usually DNA, that can be isolated from ancient human remains. Ancient remains can include skeleton parts (bones and teeth), mummified soft tissue, hair, or human-associated trace fossils, the latter of which includes fecal samples or the sediment and dirt near the remains. DNA from pathogens has been successfully isolated from almost all these biological samples but often makes up a miniscule fraction of a specimen’s total DNA – sometimes less than 0.5%. To overcome this obstacle, researchers use analytical tools, such polymerase chain reaction (PCR) to amplify small quantities DNA and match the sequences to those of known pathogens. New genomic techniques such as next generation sequencing make it possible to detect DNA from both known and novel pathogens which gives us more insight into ancient human populations and the pathogens that existed in the past.

Advances in ancient DNA analysis has proven to be a powerful tool in understanding the history of infectious diseases such as Yersinia pestis, the bacteria that causes the Black Death. There have been three separate plague pandemics that originated in different geographical areas and spread across Eurasia using different routes. The first pandemic, known as the Justinian plague of 1541, originated in central Africa, and spread east to the Mediterranean region. The second and most well-known pandemic, known simply as the Black Death of 1347, spread throughout Eurasia, and is estimated to have killed approximately 25 million people in Europe alone. The third pandemic started in 1894 in Yunnan, China and spread throughout the rest of Asia and the world.

Until recently, researchers were not sure when and where the second pandemic started. To answer this question, a team of researchers exhumed the remains from a burial site located in modern-day Kyrgyzstan believed to house victims of the fourteenth-century epidemic. The researchers sequenced the DNA that they isolated and were able to reconstruct the Yersinia pestis genome from the samples. This data provided a new geographical origin for the second plague pandemic. Discoveries like this will help steer future archaeological expeditions in the quest to trace the origins and spread of the plague.

The Yersinia pestis that exists today is not the same as it was during the past pandemics, as the pathogen has evolved over time. For example, the 700-year-old Yersinia pestis strain responsible for the Black Death pandemic is part of a lineage of Yersinia pestis strains that likely emerged 7,000 years ago. Fifty-six Yersinia pestis strains, some of which are now extinct, have been isolated over a 50-year span in present-day Kyrgyzstan alone, highlighting the complex evolutionary history of the bacteria. Evolution is an important part of pathogen biology. It is the driving force through which microbes accumulate genetic changes that help them escape the host immune response and become more effective at infecting humans. Paleomicrobiology provides a window into the past for us to understand how microbes have evolved over time and predict how they might change in the future. This information will help us be better prepared for future infectious disease outbreaks.

Paleomicrobiology is a collaborative field that combines the efforts of archaeologists, historians, and scientists to understand humans’ complex history of and relationship with infectious diseases. In the future, it will also be important to study non-infectious microbes that co-evolve with us; although these microbes typically have a positive impact on human health, they can evolve and become opportunistic pathogens under certain circumstances. Therefore, studying the evolution of seemingly harmless microbes can help predict disease emergence. As the field continues to develop, paleomicrobiology will help us better understand how microbes have and continue to impact our lives.