Smallpox left an unmistakable mark on human history, killing at least 300 million people in the 20th century alone. Despite its notoriety, the origin of the virus remains unclear.
Now a team of scientists in Italy has pushed back our best estimate of how smallpox came about by nearly 2,000 years more to check historical sources that indicate the disease has plagued human societies since ancient times, when pharaohs ruled.
Advances in genetic sequencing techniques have allowed researchers in recent years to analyze fragments of ancient viral DNA in ever greater detail, bringing them closer to understanding where and when smallpox originated.
And thanks to a lucky find in Lithuania in 2016, scientists traced smallpox back to the 15th century using viral DNA taken from the remains of a young child. And in 2020, viral DNA from Viking Age skeletons pushed back the genetic evidence for the last appearance of smallpox by a few more years, to 1050 AD.
However, historical records suggest that something like smallpox struck ancient societies even earlier. Descriptions of symptoms similar to those associated with this disease can be found in texts from fourth-century China, and Egyptian mummies with pustular scars indicate that smallpox became widespread about 3,000–4,000 years ago.
But it has been difficult to find definitive genetic evidence – like the molecular fingerprints of a virus – to support this theory.
Scientists can still draw many conclusions about the past of the virus and its evolutionary history once they have enough samples to compare. They can see how the virus has changed over time and see how quickly or slowly the virus picks up genetic mutations. From there, scientists can turn back the “molecular clock” to estimate when copies of the virus’ ancestors might have existed.
In the case of smallpox, the illness is caused by the variola virus, or VARV. In this new study, bioinformatics scientist Diego Forni from the Research Institute for Research, Hospitalization and Health (IRCCS) in Italy led a team to take another look at the genetic sequences of 54 VARV samples extracted from previously published work or from a study. database.
This includes four ancient VARV genomes from the Viking Age and two historical VARV genomes from the 17th and 18th centuries, as well as 48 modern VARV sequences prior to smallpox eradication in 1980.
Using this collection of viral sequences, the researchers reconstructed the evolutionary history of the smallpox virus, showing how it diverged from one common ancestor to various strains that either spread around the world or became extinct.
In their models, they modified the method to show that the rate of viral evolution slows down over longer periods of time and accelerates over shorter periods of time. They found that the most recent common ancestor of all VARV genomes dates back to about 3,800 years ago or earlier.
When comparing the sequences of VARV with two related orthopoxviruses, tatherapox and camelpox, the analysis also showed that the ancestor of the smallpox virus diverged from its relatives about 7,700 years ago.
The researchers say this still leaves a very wide window for smallpox to spread among humans, somewhere between 8,000 and 4,000 years ago. However, this adds to the evidence that smallpox has been around for thousands of years longer than previous analyzes of viral DNA samples suggested.
“The variola virus may be much older than we thought,” says Forney. “This is important because it confirms the historical hypothesis that smallpox was present in ancient societies.”
While these new estimates place smallpox in a suitable time frame to match historical descriptions of Egyptian pharaohs suffering from smallpox scars, there is still some uncertainty as to whether the disease was widespread at the time, as contemporary written documents contain little mention of smallpox-like symptoms. . . .
The study was published in the journal Microbial Genomics.
Source: Science Alert
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