Ancient DNA traces tuberculosis origins and what that means for emerging diseases

When ancient bones tell us where the next epidemic might start

Tuberculosis has shadowed human populations for thousands of years, and the genetic record it left behind is proving to be one of the most instructive archives we have for anticipating how infectious diseases emerge, travel, and reshape themselves. Anne Stone, a Regents Professor at Arizona State University's School of Human Evolution and Social Change, is bringing that archive to bear on questions about modern disease risk - presenting at the American Association for the Advancement of Science Annual Meeting in Phoenix.

Her presentation, titled "(Re)Emerging Pathogens: Ancient Spillovers Teach Us About Modern Plagues," draws on decades of ancient DNA analysis to trace how TB moved between animal species and human populations across continents. The patterns she has documented are not merely historical curiosities. They describe mechanisms - zoonotic spillover, sustained transmission, strain replacement - that continue to drive infectious disease today.

Seals, sailors, and strain displacement

The pre-Columbian history of tuberculosis in the Americas offers one of the clearest case studies in how disease crosses species lines and then spreads through human contact networks. Genetic evidence from ancient specimens shows that TB entered the Americas through multiple separate spillovers from pinnipeds - primarily seals - before establishing sustained human-to-human transmission. From coastal entry points, those strains moved inland and northward over generations.

Then European contact changed everything. TB lineages originating in Eurasia arrived with colonizers and, within a historically brief span, displaced the strains that had been circulating in the Americas for centuries. This was not a gradual blending of populations - it was a near-complete replacement of existing TB diversity, driven by the introduction of new strains into populations with different histories of exposure.

"Ancient genomes allow us to study infectious disease over much longer timescales than modern data alone," Stone said. "By looking at how pathogens emerged and adapted in the past, we can identify recurring patterns in the ecological and social conditions that make widespread transmission possible."

Where earlier scientists had to infer disease dynamics from skeletal lesions alone, ancient genomics now allows reconstruction of actual pathogen lineages - which strains existed, how they were related, when they diverged, and how they moved across geography.

What drives a pathogen across species lines

Stone's research sits at the intersection of several fields: ancient DNA analysis, evolutionary biology, epidemiology, and the study of human-animal interfaces. TB remains among the top ten causes of death worldwide, causing approximately 1.25 million deaths per year as of recent WHO estimates, making the evolutionary history of the pathogen directly relevant to ongoing treatment and prevention strategy.

The conditions that enabled TB to spill from seals to coastal human populations thousands of years ago are not fundamentally different from the conditions enabling zoonotic spillovers today. Dense human-animal contact, shifts in ecology, changes in social structure and population density - these factors recur across historical and contemporary disease emergence events. Understanding the specific sequence of genomic and ecological changes in past spillovers provides a template for recognizing when modern systems are entering similar configurations.

Stone also examines how human populations have responded to disease pressure over time, including genetic changes that influence susceptibility and resistance. Some populations carry genetic variants that appear to confer partial protection against certain TB lineages - variants that likely increased in frequency because they conferred a survival advantage during historical disease pressure. Mapping where those variants are most common adds another layer to understanding both past disease dynamics and present vulnerability patterns.

The limits and promises of ancient genomics

Ancient DNA analysis carries real constraints. The availability of ancient specimens is uneven - some populations and time periods are far better represented than others in the archaeological record. DNA preservation depends heavily on burial conditions, and many samples yield too little intact genetic material to sequence reliably. The geographic record skews toward regions where archaeological excavation has been extensive and where preservation conditions favor DNA survival.

Those gaps mean that conclusions about disease emergence patterns, while well-supported by available evidence, are drawn from an incomplete record. Stone's research group applies statistical modeling to account for sampling bias, but it remains a genuine limitation on how broadly any specific finding can be generalized.

What the approach does offer is the ability to test specific hypotheses about disease routes and timelines. The finding that pre-Columbian American TB strains descended from seal-associated lineages, rather than arriving overland from Asia, was controversial when first proposed. Subsequent genomic analysis from multiple independent research groups has supported the hypothesis, demonstrating how ancient DNA can resolve debates that no amount of modern clinical data could address.

From deep history to current risk

Stone directs ASU's Center for Evolution and Medicine, built on the premise that evolutionary frameworks are practical tools for understanding why disease happens when and where it does. The center brings together researchers across biology, medicine, anthropology, and public health to apply evolutionary reasoning to clinical and public health questions.

The ecological and social conditions that have historically favored spillover events continue to be present in many parts of the world. Ancient spillovers happened because humans and animals were in close contact under specific ecological conditions. Those conditions have analogs today, and the genomic signatures of past events provide a roadmap for recognizing when modern systems may be approaching similar thresholds.