A recent scientific breakthrough has provided crucial insights into a baffling ancient plague lineage, known as the Late Neolithic Bronze Age (LNBA) plague, which circulated across Eurasia for two millennia before its mysterious disappearance. The discovery of the pathogen's DNA in a 4,000-year-old sheep's tooth marks the first instance of this enigmatic plague being identified in an animal. This pivotal finding illuminates the intricate connections between domesticated animals and the ancient spread of a devastating disease, offering a fresh perspective on the pathogen's historical success in infecting human populations across vast distances and prolonged periods.

This research underscores the zoonotic nature of many human diseases, emphasizing how the close relationship between humans and animals, particularly through livestock domestication, has historically facilitated disease transmission. The LNBA plague, unlike its later counterparts, lacked key genetic components for flea transmission, making its spread a subject of scientific inquiry. The identification of this ancient plague in a sheep suggests a previously unknown wild reservoir, and points to the likelihood of spillover events from animals to humans, with pastoralist practices potentially increasing such risks. Unraveling these ancient pathways provides invaluable context for understanding current and future disease emergence and evolution.

Tracing the Origins of an Ancient Scourge

For millennia, a cryptic form of plague, identified as the Late Neolithic Bronze Age (LNBA) lineage, silently moved across the Eurasian continent, baffling scientists with its origins and eventual disappearance around 2,000 years after its first appearance. Until now, this ancient disease was only discernible through its genetic traces found in human remains, leaving researchers to speculate about its initial animal hosts and modes of transmission. A groundbreaking investigation has finally unraveled part of this puzzle, pinpointing the LNBA plague in the remains of a domesticated sheep dating back 4,000 years, discovered at the pastoralist settlement of Arkaim in the Western Eurasian Steppe. This monumental find represents the first clear evidence of this plague in an animal, fundamentally altering our understanding of its ecological history. The evidence suggests a shared source of infection for both humans and sheep—an as yet unidentified wild animal reservoir—with the expansive sheep herding practices during the Bronze Age potentially bringing these nomadic communities into more frequent contact with this hidden source. This study profoundly deepens our knowledge of the critical role played by domesticated animals in the dispersion of one of history’s most formidable bacteria, shedding light on the mechanisms that allowed it to infect populations across thousands of kilometers for thousands of years.

The vast majority of human infectious diseases known today have their roots in zoonotic events, meaning they originated in animal populations before making the leap to humans, a process referred to as spillover. A growing body of scientific data indicates that many significant infectious illnesses emerged within the last 10,000 years, a period coinciding with the domestication of various animals, including livestock and pets. This historical overlap strongly suggests that our increasingly intimate interactions with these animals were primary drivers in the genesis of human diseases. The innovative application of ancient DNA methodologies to study pathogens in ancient animal remains presents an unparalleled opportunity to meticulously investigate the historical emergence and evolution of human infectious diseases, an area that has, until recently, remained largely unexplored. The plague stands as one of the deadliest zoonotic diseases ever recorded, infamously responsible for countless deaths throughout history, most notably during the 14th-century Black Death which decimated over a third of Europe's population. However, prior to these major historical pandemics, a genetically distinct, prehistoric variant of the plague circulated across Eurasia, originating approximately 5,000 years ago. This ancient variant, known as the LNBA lineage, continued to infect human populations for nearly 3,000 years before seemingly becoming extinct. Intriguingly, the LNBA lineage lacked the specific genetic machinery necessary for flea-mediated transmission, a characteristic present in both historical and modern plague strains, thus rendering its mode of spread a persistent enigma. This critical absence implied that other animal vectors must have played a crucial role in its dissemination, prompting the fundamental question: which animals were involved? As noted by lead researcher Ian Light-Maka, a PhD candidate specializing in the long-term evolution of pathogens, a crucial initial step in comprehending disease propagation and evolution involves identifying its hidden reservoirs. Despite an extensive collection of over 200 ancient Y. pestis genomes derived from human remains, humans are not natural hosts for the plague, underscoring the necessity of exploring non-human sources.

The Critical Role of Livestock in Plague Dissemination

In an effort to unravel the mystery of how the LNBA plague persisted and spread across Eurasia for millennia, an international consortium of researchers embarked on an ambitious project. Their investigation focused on the bones and teeth of Bronze Age livestock from the pastoralist site of Arkaim, located in Russia within the Eurasian Steppe, a region historically associated with the Sintashta-Petrovka culture, renowned for its advancements in cattle, sheep, and horse husbandry. It was here that they made a pivotal discovery: a 4,000-year-old sheep infected with the identical LNBA lineage of Yersinia pestis that was simultaneously afflicting human populations. As Dr. Taylor Hermes, Assistant Professor of Anthropology at the University of Arkansas and a co-author of the study, remarked, Arkaim presented an ideal location to search for clues regarding the plague's spread. The Sintashta-Petrovka culture represented early pastoralist societies that lacked the grain storage systems typically conducive to attracting rats and their flea populations, yet previous evidence indicated Y. pestis infections among Sintashta individuals. This suggested a strong possibility that livestock could be the crucial missing link in the transmission chain.

A detailed comparison of the newly sequenced ancient Y. pestis genome from the sheep with existing ancient and contemporary genomes revealed a remarkable similarity to a strain that had infected a human at a nearby archaeological site around the same period. Dr. Christina Warinner, Landon T. Clay Professor of Scientific Archaeology at Harvard University and a group leader at the Max Planck Institute for Evolutionary Anthropology (MPI-EVA), highlighted the striking resemblance: "If we didn't know it was from a sheep, everyone would have assumed it was just another human infection—it's almost indistinguishable." This profound genetic congruence indicates that both humans and their animals were contracting infections from the same circulating population of Y. pestis, prompting the critical question of who infected whom. Insights gleaned from archaeological findings and comparative analyses offer some answers. In regions where Y. pestis remains endemic today, it is well-established that sheep can contract the infection through direct exposure to the carcasses of infected wild animals, such as rodents, which serve as the natural reservoir for the pathogen. Such infections in livestock can subsequently trigger localized plague outbreaks in human communities, particularly if proper butchering or cooking practices are not observed. A similar scenario could plausibly explain the wide dissemination of the LNBA plague during prehistory, creating a direct link between animal and human infections. Dr. Warinner further elaborated on the Bronze Age context, noting that the Sintashta-Petrovka culture was celebrated for their extensive herding across vast pasturelands, facilitated by innovative horse technologies. This widespread grazing provided ample opportunities for their livestock to encounter wild animals harboring Y. pestis, creating a short, direct pathway for the pathogen's leap into human populations. The analysis of the new sheep Y. pestis genome, in conjunction with existing human-derived genomes, allowed for a more comprehensive reconstruction of the evolutionary dynamics of this ancient, and presumed extinct, plague lineage. Contrary to modern Y. pestis lineages, which exhibit considerable geographical variability and distinct genetic characteristics, the ancient LNBA lineage displayed remarkable genetic uniformity across its vast range of nearly 6,000 kilometers at any given time. This widespread homogeneity, despite such immense distances, suggests unique evolutionary pressures or transmission mechanisms. While differences in life cycle and natural selection could certainly have played a role, given that in many well-understood pathogens, like SARS-CoV-2 (the virus responsible for COVID-19), new variants emerge and rapidly spread if they enhance infection or transmission efficiency, the study unexpectedly found the opposite pattern. The ancient lineage appeared to be evolving under strong genetic constraints. Notably, a specific subset of genes exhibited repeated and independent mutations, but these parallel changes were observed exclusively in infections that did not produce direct evolutionary descendants. This intriguing pattern might represent a distinct genetic signature of past spillover events from an unknown, persistent reservoir. As Dr. Felix M. Key, senior author and head of the Evolutionary Pathogenomics Lab at the Max Planck Institute for Infection Biology (MPIIB), summarized, the ancient lineage evolved under elevated pressure, a stark contrast to the dynamics seen in contemporary Y. pestis strains. Furthermore, both the ancient sheep and human infections are likely isolated spillover incidents from an elusive wild reservoir that still remains undiscovered. Identifying this reservoir is considered the next crucial step in understanding the full scope of this ancient pathogen. Despite these profound new insights, significant questions continue to persist, particularly concerning how the pathogen managed to spread so widely and rapidly over short timeframes. It is improbable that sick humans or terrestrial animals like sheep were the sole or primary vectors for such extensive dissemination, especially given instances of nearly identical LNBA Y. pestis genomes found thousands of kilometers apart but from the same time period—distances far too great for an infected individual or animal to traverse. Fortunately, the exploration of ancient pathogens in animal remains is still in its nascent stages. Archaeological excavations routinely yield tens of thousands of animal bones, and countless samples from past digs are housed in storerooms, awaiting further scientific scrutiny. Dr. Key expressed optimism about the future of this research, stating that he anticipates a growing interest in analyzing these invaluable collections, as they offer unique insights that no human sample alone can provide into the deep history of infectious diseases."