The pathogen landscape of the Neolithic and its influence on the human immune gene pool

Emerging and re-emerging diseases have increased rapidly and became a major problem in recent years. They are a burden on humanity, not only in terms of health but also financially. As pathogenic microorganisms evolve to evade their human hosts' immune systems, humans in turn selected for defense mechanisms against these harmful microbes, resulting in a reciprocal evolutionary arms-race. To gain a deeper understanding of this longstanding co-evolution, it is necessary to investigate the origins of the sedentary lifestyle and the advent of human-animal co-habitation – the Neolithic period. As such, the introduction of animal husbandry and the resulting close proximity of humans and their animals in a confined space is often seen as the prerequisite for an increased incidence of infectious diseases in the form of zoonoses. To determine when infectious diseases appeared, their prevalence, and links to transformations, 1,216 human and animal skeletal remains from prehistoric Europe were analysed for genetic traces of bacterial and viral agents. Immunogenetic profiles of the HLA region were generated for six prehistoric populations to study shifts in immune gene composition as indicators of pathogen-driven selection. Until the Late Neolithic (~4,000 BCE), Europe’s pathogen landscape was dominated by viral pathogens, reflected in low immunogenetic diversity favoring viral protection. From the Late Neolithic onward, bacterial infections increased slightly but were isolated zoonoses or infections from consuming infected animals, with little epidemic potential. Following the migration of Yamnaya steppe pastoralists into Europe, immunogenetic profiles showed increased HLA allele diversity, suggesting a more varied pathogen landscape. There is insufficient evidence to claim Neolithization directly triggered emerging infectious diseases, but the Neolithic period likely set the stage for later developments leading to large-scale outbreaks.

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