Summary
The current 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 COVID-19.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
We revised the title; WE addressed more directly multiple misconceptions about the results that arose on social media; We corrected a mis-specified parameter when using CLUES (the time cutoff tCutOff, pushed from 1,000 to 1,500 generations) to allow inference of older non-zero allele frequencies and Figure 3 has been revised accordingly; We added the frequency trajectories estimated by CLUES in the Yoruba and in the British populations; We added a supplemental table with the current frequencies of the selected alleles in Africa, Europe and East Asia, together with the corresponding SNP IDs; We added justifications about why we use the UK Biobank COVID-19 GWAS instead of other alternatives to avoid population stratification issues as much as possible.
