An ancient viral epidemic involving host coronavirus interacting genes more than 20,000 years ago in East Asia

Abstract

14 The current SARS-CoV-2 pandemic has emphasized the vulnerability of human 15 populations to novel viral pressures, despite the vast array of epidemiological and 16 biomedical tools now available. Notably, modern human genomes contain evolutionary 17 information tracing back tens of thousands of years, which may help identify the viruses 18 that have impacted our ancestors – pointing to which viruses have future pandemic 19 potential. Here, we apply evolutionary analyses to human genomic datasets to recover 20 selection events involving tens of human genes that interact with coronaviruses, 21 including SARS-CoV-2, that likely started more than 20,000 years ago. These adaptive 22 events were limited to the population ancestral to East Asian populations. Multiple lines 23 of functional evidence support an ancient viral selective pressure, and East Asia is the 24 geographical origin of several modern coronavirus epidemics. An arms race with an 25 ancient coronavirus, or with a different virus that happened to use similar interactions as 26 coronaviruses with human hosts, may thus have taken place in ancestral East Asian 27 populations. By learning more about our ancient viral foes, our study highlights the 28 promise of evolutionary information to better predict the pandemics of the future. 29 Importantly, adaptation to ancient viral epidemics in specific human populations does 30 not necessarily imply any difference in genetic susceptibility between different human 31 populations, and the current evidence points toward an overwhelming impact of 32 socioeconomic factors in the case of COVID-19. 33 34