Abstract
The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has emphasized the vulnerability of human populations to novel viral pressures, despite the vast array of epidemiological and biomedical tools now available. Notably, modern human genomes contain evolutionary information tracing back tens of thousands of years, which may help identify the viruses that have impacted our ancestors—pointing to which viruses have future pandemic potential. Here, we apply evolutionary analyses to human genomic datasets to recover selection events involving tens of human genes that interact with coronaviruses, including SARS-CoV-2, that likely started more than 20,000 years ago. These adaptive events were limited to the population ancestral to East Asian populations. Multiple lines of functional evidence support an ancient viral selective pressure, and East Asia is the geographical origin of several modern coronavirus epidemics. An arms race with an ancient coronavirus, or with a different virus that happened to use similar interactions as coronaviruses with human hosts, may thus have taken place in ancestral East Asian populations. By learning more about our ancient viral foes, our study highlights the promise of evolutionary information to better predict the pandemics of the future. Importantly, adaptation to ancient viral epidemics in specific human populations does not necessarily imply any difference in genetic susceptibility between different human populations, and the current evidence points toward an overwhelming impact of socioeconomic factors in the case of coronavirus disease 2019 (COVID-19).
Highlights
Coronaviruses have been behind three major zoonotic outbreaks.[1]
Here, we investigate whether ancient coronavirus epidemics have driven past adaptation in modern human populations, by examining whether selection signals are enriched within a set of 420 virus-interacting proteins (VIPs) that interact with coronaviruses across 26 human populations from the 1000 Genomes Project.[18]
The significance of the whole enrichment curve is calculated using a genome block-randomization approach that accounts for the genomic clustering of neighboring CoV-VIPs and provides an unbiased false-positive risk (FPR) for the whole enrichment curve[28] by re-running the entire enrichment analysis pipeline on block-randomized genomes (STAR Methods).[17]
Summary
Coronaviruses have been behind three major zoonotic outbreaks.[1] The first outbreak, known as SARS-CoV (severe acute respiratory syndrome coronavirus), originated in China in 2002 and infected more than 8,000 and killed more than 800 people.[2] Four years later, MERS-CoV (Middle East respiratory syndrome coronavirus) affected >2,400 and killed over 850 people (https:// www.who.int). The most recent outbreak began in late 2019 when SARS-CoV-2 emerged in China, triggering an ongoing pandemic (coronavirus disease 2019 [COVID-19]).[3]. The research on SARS-CoV-2 epidemiology has revealed that socioeconomic (e.g., access to healthcare, testing, and exposure at work), demographic, and personal health factors all play a major role in SARS-CoV-2 epidemiology.[4,5,6] several genetic loci that mediate SARS-CoV-2 susceptibility and severity have been found in contemporary European populations,[7,8,9,10] one of which contains a genetic variant that increases SARS-CoV-2 susceptibility that likely increased in frequency in the ancestors of modern Europeans after interbreeding with Neanderthals.[11]
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