COVID-19 Genetics: Australian Led Study Indicates That East Asians May Have Genetically Adapted To The Coronavirus Since 25,000 Years Ago

COVID19 Genetics: Scientists from the University of Adelaide-Australia, Australian National University and the University of Arizona-United States have in a new study found that that an ancient coronavirus-like epidemic drove the adaptation of East Asian people from 25,000 to 5,000 years ago.


 
The present 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, the study team applies evolutionary analyses to human genomic datasets to recover selection events involving tens of human genes that interact with coronaviruses, including SARS-CoV-2, that started 25,000 years ago. These adaptive events were limited to ancestral East Asian populations, the geographical origin of several modern coronavirus epidemics. An arms race with an ancient corona-like virus may thus have taken place in ancestral East Asian populations. By learning more about ancient viral foes, the study highlights the promise of evolutionary information to combat the pandemics of the future.
 
The study findings were published on a preprint server and have yet to be peer reviewed. https://www.biorxiv.org/content/10.1101/2020.11.16.385401v1
 
Just over the past twenty years, strains of coronaviruses created three major outbreaks with significant human impacts. The first outbreak, the severe acute respiratory syndrome (SARS), occurred in China in 2002. The epidemic infected over 8,000 people and claimed nearly 800 lives.
 
A few years later, the Middle East respiratory syndrome (MERS) affected about 2,400 people and caused over 850 deaths in Saudi Arabia.
 
However the most recent outbreak started in December 2019 in Wuhan City in China. Though less virulent and deadly, the coronavirus disease is far more contagious. The outbreak has caused over 56.2 million people and at least 1.35 million deaths.
 
As a result of the magnitude of the current pandemic, research efforts have been mounted to develop new vaccines and therapies to curb its impact. Some scientists have focused on determining the factors that underlie the infection's epidemiology.
 
Previous research and evidence suggests that ancient viral epidemics have occurred regularly in the history of the humanity. However, it remains unclear if this has made a marked contribution to population-level differences in SARS-CoV-2 responses today.
 
The study team investigated whether ancient coronavirus epidemics have generated genetic differences within and across modern human populations.
The team investigated if selection signals are enhanced within a set of VIPs (virus-interacting proteins) specific to the coronavirus. They scanned 26 diverse human populations from five continents to prove strong selection acting on proteins that interact with coronavirus strains (CoV-VIPs).
 
The researchers identified 42 CoV-VIPs manifesting a coordinated adaptive response th at emerged way back (around 25,000 years ago), equating to 900 generations.
 
The pattern seen was unique to the ancestors of East Asians. The team also noted that the selection pressure created a robust response across the 42 CoV-VIPs genes.
 
The study team explained that the adaptive response is probably the result of a multigenerational coronavirus epidemic.
 
The study analyses suggest that the 42 CoV-VIPs identified as putative targets of an ancient coronavirus (or related virus) epidemic might play a functional role in SARS-CoV-2 etiology in modern human populations. The team found that four of these genes (SMAD3, IMPDH2, PPIB, GPX1) are targets of eleven drugs being currently used or investigated in clinical trials to mitigate COVID-19 symptoms (STAR methods).
 
While this number is not higher than expected when compared to other CoV-VIPs (hypergeometric test P>0.05), the team notes that most of the 42 genes  identified here have yet to be the focus of clinical trials for SARS-CoV-2-related drugs. In addition to the four selected CoV-VIP genes targeted by coronavirus-specific drugs, five additional selected CoV-VIP genes are targeted by multiple drugs to treat a variety of non-coronavirus pathologies. This raises the possibility that such drugs could be repurposed for therapeutic use in the current SARS-CoV-2 pandemic. Indeed, an additional six of the 42 selected CoV-VIPs have been identified by as part of the “druggable genome.” https://pubmed.ncbi.nlm.nih.gov/28356508/
 
Interestingly one feature of the adaptive response seen is that selection appears to be continuously happening over 20,000 years. This means that coronavirus pandemics have been occurring throughout history. For instance, in recent years, coronavirus epidemics occurred approximately every decade, suggesting that the pattern may have occurred throughout history in East Asian peoples.
 
The researchers concluded that they could infer ancient viral epidemics affecting the ancestors of East Asian populations. This resulted in coordinated adaptive chances across at least 42 genes.
 
The study team explained, "The study findings highlight the utility of incorporating evolutionary genomic approaches into standard medical research protocols. Indeed, by revealing the identity of our ancient pathogenic foes, evolutionary genomic methods may ultimately improve our ability to predict and thus prevent the epidemics of the future.”
 
Importantly understanding how populations respond to the current pandemic can help scientists develop new therapies and vaccines to curb its spread.
 
By leveraging the evolutionary information contained in publicly available human genomic datasets, the study team was able to infer ancient viral epidemics impacting the ancestors of contemporary East Asian populations, which initially arose around 25,000 years ago, resulting in coordinated adaptive changes across at least 42 genes. Importantly, this evolutionary genomic analysis has identified several new candidate genes that might benefit current efforts to combat COVID 19, either by providing novel drug targets or by repurposing currently available drugs that target these candidate genes. More broadly, this findings highlight the utility of incorporating evolutionary genomic approaches into standard medical research protocols.  Indeed, by revealing the identity of our ancient pathogenic foes, evolutionary genomic methods may ultimately improve the ability to predict and thus prevent the epidemics of the future.

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