The genomes of multiple East Asian populations bear the signature of a viral epidemic that occurred approximately 900 generations, or 25,000 years (28 years per generation) ago, according to a new study published in the journal Current Biology.
Souilmi et al. 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. Image credit: Souilmi et al., doi: 10.1016/j.cub.2021.05.067.
Throughout the evolutionary history of Homo sapiens, positive natural selection has frequently targeted proteins that physically interact with viruses — e.g., those involved in immunity or used by viruses to hijack the host cellular machinery.
In the millions of years of human evolution, selection has led to the fixation of gene variants encoding virus-interacting proteins (VIPs) at three times the rate observed for other classes of genes.
Strong selection on VIPs has continued in human populations during the past 50,000 years, as evidenced by VIP genes being enriched for adaptive introgressed Neanderthal variants and also selective sweep signals (i.e., selection that drives a beneficial variant to substantial frequencies in a population), particularly around VIPs that interact with RNA viruses, a viral class that includes the coronaviruses.
The accumulated evidence suggests that ancient RNA virus epidemics have occurred frequently during human evolution. However, scientists currently do not know whether selection has made a substantial contribution to the evolution of human genes that interact more specifically with coronaviruses.
“The modern human genome contains evolutionary information tracing back tens of thousands of years, like studying the rings of a tree gives us insight into the conditions it experienced as it grew,” said Professor Kirill Alexandrov, a researcher at the CSIRO-QUT Synthetic Biology Alliance and the Centre for Genomics and Personalised Health at the Queensland University of Technology.
In the study, Professor Alexandrov and colleagues used data from the 1000 Genomes Project, which is the largest public catalogue of common human genetic variation.
They examined whether selection signals are enriched within a set of 420 VIPs that interact with coronaviruses (such as SARS-CoV-2) across 26 human populations.
These coronavirus VIPs comprise 332 SARS-CoV-2 proteins identified by high-throughput mass spectrometry and an additional 88 proteins that were manually curated from literature.
Their analysis revealed a strong enrichment in sweep signals at coronavirus VIPs across multiple East Asian populations, which is absent from other populations.
This suggests that an ancient coronavirus epidemic — or another virus using similar VIPs — drove an adaptive response in the ancestors of East Asians.
The researchers found that 42 coronavirus VIPs may have come under selection around 900 generations (25,000 years) ago and exhibit a coordinated adaptive response.
“We applied evolutionary analysis to the human genomic dataset to discover evidence that the ancestors of East Asian people experienced an epidemic of a coronavirus-induced disease similar to COVID-19,” Professor Alexandrov said.
“In the course of the epidemic, selection favored variants of pathogenesis-related human genes with adaptive changes presumably leading to a less severe disease.”
“By developing greater insights into the ancient viral foes, we gain understanding of how genomes of different human populations adapted to the viruses that have been recently recognized as a significant driver of human evolution.”
“Another important offshoot of this research is the ability to identify viruses that have caused epidemic in the distant past and may do so in the future.”
“This, in principle, enables us to compile a list of potentially dangerous viruses and then develop diagnostics, vaccines and drugs for the event of their return.”
Yassine Souilmi et al. An ancient viral epidemic involving host coronavirus interacting genes more than 20,000 years ago in East Asia. Current Biology, published online June 24, 2021; doi: 10.1016/j.cub.2021.05.067