Tracing the Millennia-Long Evolution of Betaherpesvirus 6A and 6B Through Ancient DNA Analysis

The exploration into the ancient DNA of Human Betaherpesviruses 6A and 6B is a journey through time, revealing the lasting impact of these viruses on human populations. Researchers have unearthed nine full and two partial ancient viral genomes spanning from the Italian Iron Age to medieval Europe, providing insights into the deep history of these pervasive viruses that have silently shadowed human migration for over two millennia.
The study spans a remarkable range of archaeological sites across Europe, each telling its own unique story of viral evolution and human history. Notably, an individual from Iron Age Italy, represented by the sample ORD001, marks the oldest genome discovered, dating back to at least the 8th century BCE. This young girl from the Ordona site represents one of the most ancient examples of HHV-6 integration in human populations.
Further discoveries at sites like Edix Hill in England and Sint-Truiden in Belgium offer unique glimpses into the lives of past populations, where each skeleton tells its own compelling story. EDI001, a teenage male from the Anglo-Saxon site of Edix Hill, is particularly fascinating as he lived during a period infamous for being a hotspot during the First Plague Pandemic, revealing co-infections with the deadly Yersinia pestis alongside HHV-6.
This comprehensive study showcases a remarkable spectrum of historical and cultural contexts spanning the entire European continent. From a medieval Estonian woman discovered on the island of Saaremaa to a child from 14th century Cambridge found at the medieval Hospital of St. John the Evangelist, each individual marks a crucial point on the human map of viral evolution and cultural exchange.
Sint-Truiden stands out as a particularly significant site with multiple infected individuals, emphasizing the historical propagation of these viruses in European communities. The sprawling medieval parish graveyard provided researchers with several carriers of ancient viruses, creating a patchwork of stories from medieval Europe's rich cultural fabric.
The research extends even further into remote regions, including discoveries in Russia's Komi Republic, where taiga hunter-fisher-gatherers carried these ancient viruses. This finding highlights the extraordinary broad reach of these viruses across diverse populations and lifestyles, from settled agricultural communities to nomadic hunter-gatherer societies.
These viruses are particularly fascinating due to their remarkable ability to integrate into the human genome, with potential transmission across generations like inherited heirlooms shaped by life's relentless ebb and flow. The research reveals that by the 14th century CE, large fractions of modern HHV-6 diversity were already firmly established in human populations.
The study demonstrates how archaeological and osteological elements provide crucial insights into the presence and effect of HHV genotypes throughout history. Viral sequences detected within dense bone structures, particularly petrous bones with their low remodelling potential, provided compelling evidence for the likelihood of inherited virus strains that have been passed down through countless generations.
Among the samples analyzed, the petrous bone of ORD001 provides invaluable clues about inherited viral traits spanning millennia. Typically utilized for its exceptionally high DNA yield, the petrous bone has proven to be a crucial tool in ancient viral research, enabling scientists to detect viral traces in ancient remains with remarkable reliability and precision.
This meticulous approach to bone analysis has revolutionized our understanding of how viruses integrated and evolved within human hosts, suggesting historical pathways through which these persistent viruses adapted and flourished alongside human populations across diverse geographical and cultural landscapes.
Each carefully extracted genome contributes to a broader, more comprehensive narrative of how these viruses evolved in human populations over the course of 2,500 years. Some samples, such as the remarkable ORD001, indicate a wide divergence from modern reference sequences, pointing to the dynamic, ever-shifting landscape of viral evolution throughout human history.
The analysis helps identify specific integration sites and establish that certain ancient clades have been present for millennia but are surprisingly less active today among contemporary European populations. This finding suggests significant shifts in viral activity and prevalence over historical timescales.
Through the lens of cutting-edge technology and scientific innovation, ancient DNA analysis has ventured far beyond just a glimpse into antiquity. By reconstructing complete genomes from skeletal remains, researchers have illustrated just how deeply rooted these viruses are within the very fabric of human history and evolution.
The science extends well beyond initial discovery into comprehensive analysis and interpretation. Intensive efforts have been meticulously focused on understanding the integration and evolution of these viruses within the human genome across vast temporal and geographical scales. By comparing ancient genomes with modern sequences, researchers have unveiled fascinating evolutionary patterns that trace human migrations and population shifts from early human history right up to contemporary times.
This genomic dance across centuries reveals the viruses' remarkable ability to shift and persist alongside humanity through major historical transitions, cultural changes, and population movements. The integration and evolution of these viruses within human hosts suggest complex historical pathways of adaptation and survival.
https://www.biorxiv.org/content/10.1101/2024.06.25.599715v1.full
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