Genomic analysis of ancient remains has shed light on the origins of the black death and offers insights into the coevolution of humans and diseases.

What the DNA of Ancient Humans Reveals About Pandemics

GEORGES GOBET

As an earth scientist specializing in ancient remains, Christopher Hunt is used to making unusual trips in the name of archaeology. But one of his most memorable has to be the time he traveled back from Iraq with a Neanderthal in the plane seat next to him.

“She was packed carefully away in a large suitcase, but checking her into the hold seemed far too risky—so I bought her a passenger ticket,” he says by way of explanation. Shanidar Z, as the Neanderthal was named, is the latest ancient skeleton to be excavated from Shanidar Cave in the Kurdish region of northern Iraq, where Hunt and a small team of local and international researchers have been working since 2014.

Shanidar is a significant archaeology site first made famous by the discovery of 10 Neanderthal remains around 60 years ago. Back then, archaeologists relied on carbon-dating methods to analyze findings, which required several jars’ worth of material to be sampled and took up to six months to get a result. These days, much of the team’s research centers around genomic sequencing—the processing of tiny samples of ancient DNA, typically from a piece of fossilized bone. The process can be used to map out the whole genomes (or at least parts of them) of ancient humans or their Neanderthal neighbors.

Ancient genomics may not typically make for glamorous headlines—modern human health advances are far more likely to dominate mainstream media—but interest in the field is growing. Increasingly, ancient DNA studies are revealing as much about the world we live in now as the one experts imagine existed several thousand years ago.

Take our understanding of infectious diseases. This summer, ancient DNA taken from bubonic plague victims buried in Central Asia has helped to pinpoint an area of northern Kyrgyzstan as ground zero for the black death. By using genomics to reconstruct the genes of ancient plague bacteria responsible for tens of millions of deaths in the 14th century, bio-historians have discovered that these pathogens have genetic links to most of the plague strains still in existence today.

The lesson here, according to the study’s coauthor Johannes Krause, director of the Max Planck Institute for Evolutionary Anthropology in Germany, is that “we should not underestimate the potential of pathogens to spread around the world from rather remote locations, likely due to a zoonotic event.” That is to say, infectious diseases jumping from animals to people—as is suspected to have happened with Covid-19—and then spreading far and wide is a problem that dates back centuries.

Until recently, many scientists had been skeptical about the value of attempting to sequence ancient DNA: Samples are often so old that the DNA strands have become degraded and fragile or else contaminated; the process is much more laborious and costly as a result.

Many early studies of ancient DNA were therefore done with mitochondrial DNA. This genetic material—housed in the mitochondria, the power plants of our cells, and passed from mother to child—offered more reliable data. But advances in sequencing technology means more recent studies have also been able to use Y-chromosome (male) DNA, which is typically more repetitive and difficult to read. The result is a more accurate overview of genetic changes over time, and it is this approach that Shanidar Z should benefit from.

After Hunt’s unusual flight home, Shanidar Z made it safely to the University of Cambridge for digital scanning and will eventually be transferred back to northern Iraq to feature as the centerpiece of a new museum. The skeleton could be up to 90,000 years old, but its DNA will be used to further understanding of modern human history—by analyzing and statistically comparing the ancient DNA against the genomes of modern populations, “to demonstrate when different population groups parted company,” Hunt says.

Once a population splits into two or more reproductively isolated groups, the genes in each new population will evolve gradually in new directions as a result of random gene mutations as well as exposure to various environmental factors that prevent successful reproduction—coming into contact with new diseases, for instance.

It’s through work like this that scientists have been able to chart the migration of different populations of humans and Neanderthal groups around the planet over the last 70,000 years, and also bust some myths about their habits and migration patterns. We now know that humans and Neanderthals interbred quite commonly, and that Neanderthal communities were likely more caring and intelligent than we’ve previously given them credit for. According to Hunt, evidence of burial rituals at the Shanidar Cave “suggests memory, and that they looked after their injured and sick members.”

Separately, analysis of ancient DNA against the modern human genome has revealed that we still carry some genetic sequences that were present in people living millennia ago. Such analysis even helped to identify a new subspecies of humans 12 years ago—this discovery of Denisovans, believed to have existed across Asia around 400,000 years ago, demonstrates how much is still unknown about our human origins.

At the Francis Crick Institute in London, a major project is underway to create a reliable biobank of ancient human DNA to help build on such discoveries. Population geneticist Pontus Skoglund is leading the £1.7 million ($2.1 million) project, which will sequence 1,000 ancient British genomes by gathering data from skeletal samples from the past 5,000 years, with help from around 100 other UK institutions. From the database he hopes to determine how human genetics have changed over millennia in response to factors such as infectious diseases and changes in climate, diet, and migration.

“Part of that is looking for genetic traits that may have been advantageous for past humans during earlier epidemics,” he says. “There is no doubt we can learn something from this in our understanding of how we manage contemporary disease and other outbreaks.”

Skoglund’s team sources their samples from archaeological digs around the country or from museums with existing collections. His favorite bones to sequence are the ones found in our inner ear: “These are particularly good at preserving DNA, since they are the least susceptible to microbial invasion and other factors that could cause DNA to deteriorate,” he explains.

The bones are ground down to be run through a sequencing machine in much the same way as any DNA sample. But the ancient DNA requires “specialist protocols—modern DNA has very long fragments that are basically intact, whereas with ancient DNA we only get on average around 35 percent of the total base pairs.”

The team are also working with new ways to mitigate contamination in ancient samples—opening up a whole new avenue of more reliable data analysis. This is particularly useful when looking at the existence of diseases in ancient humans. Some disease-causing microbes that infected ancient humans will have left lesions on their bones—and within those lesions, the genetic material of some of those pathogens will have survived. In searching for ancient pathogens that don’t leave these distinctive lesions, researchers will often look into the dental pulp inside teeth. “Often the best approach to detecting them is to sequence all the DNA we can get from our sample—which will often contain microbial DNA from the soil and present-day contamination,” explains Pooja Swali, a PhD researcher in Skoglund’s lab.

When the researchers have their “soup” of DNA, they use metagenomics—genomic analysis of microorganisms in the sample—to identify all the ingredients. If they detect something that causes disease, the finding then goes through authentication checks to make sure it’s genuinely ancient, Swali explains. “We can then enrich these samples by using specially designed baits to fish out the pathogen DNA out of our soup.”

Isolating the pathogen DNA in this way allows researchers to reconstruct its genome—and identify how it differs genetically from pathogens today. The project is already producing promising results: a preprint paper currently under review reveals the discovery of what is believed to be the oldest plague in Britain, dating back almost 3,000 years before the black death.

It’s Skoglund’s hope that such deep genomic analysis will help to build a more accurate version of human history, and also offer some lessons on past mistakes, particularly when it comes to incidents like pandemics. “It might even shed new light into immune biology from an evolutionary perspective,” he says. For example, with bubonic plague, “we can see that some genetic variants involved in immunity changed frequency and allowed humans to respond better to these threats.” In essence, his team’s analysis paints a picture of how diseases can impact human evolution.

“Ancient genomics can offer some really exciting clues into disease control,” Skoglund says. “It’s going to be a vital tool in our understanding of who we are and our survival as a species.”

Rachael Pells is the author of Genomics: How Genome Sequencing Will Change Our Lives. Find out more and order your copy of the book.

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