Ancient Pathogen Genomics

Ancient pathogen genomics recovers the genomes of microbes from skeletal and other remains, revealing the identity, antiquity, and evolution of past epidemics such as plague, tuberculosis, and leprosy.

Definition

The recovery and analysis of pathogen genomes from archaeological remains, used to identify past infections, date their emergence, and reconstruct the evolutionary history and spread of infectious diseases.

Scope

This topic covers the detection and reconstruction of pathogen genomes from archaeological human remains: enriching and sequencing microbial DNA, confirming diagnoses suspected from bone lesions, dating the emergence of diseases, and reconstructing the phylogeny and spread of pathogens such as Yersinia pestis. It bridges paleopathology, archaeogenetics, and the history of infectious disease.

Core questions

• How are pathogen genomes detected and reconstructed from ancient remains?
• How does genomic evidence confirm or revise paleopathological diagnoses?
• When did major human pathogens emerge and how did they spread?
• What does ancient pathogen evolution reveal about virulence and host adaptation?

Key theories

Genomic confirmation of historical epidemics

The reconstruction of pathogen genomes from victims—such as Yersinia pestis from Black Death burials—provides direct molecular confirmation of the causative agent of past epidemics and anchors their phylogeny.

Deep-time phylogenetics of disease

Using dated ancient genomes as calibration points to reconstruct when pathogens emerged, diversified, and spread, refining molecular clocks and the evolutionary history of infectious disease.

History

Early molecular detection of pathogens such as tuberculosis used targeted PCR, but the field was transformed by genome-scale work from around 2011, beginning with the reconstruction of a Black Death plague genome. Subsequent studies reconstructed ancient genomes of plague, leprosy, tuberculosis, and other pathogens, as reviewed by Spyrou and colleagues.

Debates

Reliability and interpretation of ancient pathogen identifications

How to guard against false-positive pathogen detection from environmental microbes, and how to interpret the absence of expected pathogen DNA, given uneven preservation and the limits of metagenomic screening.

Key figures

• Kirsten I. Bos
• Maria A. Spyrou
• Johannes Krause
• Christina Warinner

Seminal works

• bosetal2011
• spyrouetal2019
• orlandoetal2021

Frequently asked questions

How can a microbe from centuries ago be sequenced?

Pathogen DNA can survive in the teeth and bones of infected individuals, and by enriching and sequencing this material researchers can reconstruct microbial genomes, as was done for the Black Death plague bacterium.

What does ancient pathogen DNA add to paleopathology?

It can confirm which microbe caused lesions seen on bone, detect infections that leave no skeletal trace, and reveal how diseases evolved and spread over time.