Delving into the genetic past, a groundbreaking study published in Nature reveals that Northern Europeans’ heightened susceptibility to multiple sclerosis (MS) traces back 5,000 years, an evolutionary consequence of transitioning to sheep and cattle herding. By comparing ancient and modern genomes, scientists unveil the protective mutations that once shielded ancestors from pathogens but now contribute to autoimmune diseases. Though the research doesn’t prescribe new drugs, it underscores the need to recalibrate immune cells rather than suppressing them entirely, offering a novel perspective for treating MS and potentially other autoimmune conditions.
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Ancient DNA Could Be Hiding All Kinds of Health Secrets: Lisa Jarvis
By Lisa Jarvis
In a paper published this week in Nature, part of an impressive series of insights about ancient peoples, researchers compared thousands of ancient and modern genomes to unearth new information about multiple sclerosis. The findings help the scientists make the case that Northern Europeans’ elevated risk of MS is a 5,000-year-old relic of becoming sheep and cattle herders. It turns out that the mutations that make some people more vulnerable to the neurological condition once had a useful function, protecting their ancestors from pathogens.
In other words, in battling certain diseases, we’re up against thousands of years of evolution. No wonder finding good medicines is such a slog.
The work is an amazing technological feat, beautifully laying out a blueprint for how to use large sets of ancient genomes to probe the origins and spread of disease. And while that won’t directly lead to new medicines, insights from ancient ancestors can help shape our thinking about treatment. What new revelations about human health and disease might lie not in our own individual genomes, but in comparing our DNA to our ancient ancestors’ or even to those of other species?
By extracting genetic material from the bones and teeth of several hundred specimens borrowed from museums, and pooling that with genomic data on other ancient Europeans, the research team were able to trace back the introduction of genetic risk factors for multiple sclerosis. They found a distinct signal about 5,000 years ago, when steppe herders migrated into Northern Europe.
The data suggests that the introduction of farm animals into everyday life exposed people to new pathogens, which in turn led to the protective mutations that pepper the genomes of descendants from that population. But our lifestyle has radically changed in the past 200 years. Basic hygiene is vastly different — we aren’t loaded up with parasites, and the advent of antibiotics and vaccines has saved countless lives. Yet that also means our immune systems simply aren’t under the same kind of constant threat as in the past. And while “the threat is removed, our genome and our biology doesn’t move as fast,” explains Samira Asgari, a geneticist who studies infection and immunity at the Icahn School of Medicine at Mount Sinai.
The result? Those same variants that were meant to protect ancient farmers from infection “have today almost turned against us,” says Maanasa Raghavan, who studies ancient DNA at the University of Chicago.
The notion that autoimmune diseases are a relic of an ancient culture’s exposure to infections isn’t new. But this paper provides “the first and biggest empirical evidence to support the hypothesis,” Raghavan says.
Researchers trying to find better drugs for MS now have a better idea of what they’re up against when it comes to certain autoimmune diseases. As explained by Lars Fugger, a neurologist at the University of Oxford who was involved in the study, scientists are trying to undo 5,000 years of evolutionary honing.
Unfortunately, the research doesn’t offer a roadmap for how to design new and better drugs. But Lugger suggests that the work might at least point to a better way. Current MS therapies generally work by damping down the immune system, but given that these mutations arose to protect us, perhaps the better approach would be to recalibrate immune cells’ activity rather than shutting them down altogether.
Ideally, with these data in hand — and eventually made available to other researchers — an exploration other health conditions will unfold. The signal of risk won’t always be as clear and meaningful as with MS, but there are plenty of diseases where this type of data can be used to solidify hypotheses and illuminate biology.
As that work evolves, the field must do better a job of expanding the study of ancient (and modern) DNA beyond Europe and North America. Although all humans are genetically very similar, our evolutionary pasts might differ — and, as this MS paper nicely highlights, those histories can affect our understanding of current health issues.
Some of the focus on European ancestors is practical. Ancient DNA is better preserved in colder, drier climates, making it harder to extract useful genetic information from samples in, for example, the tropics. But researchers say funding for projects in less-represented populations has lagged significantly.
The problem is not limited to ancient DNA. Much of the work in modern genetics has been devoted to studying people outside of North America and Europe. Asgari points out that 80% of large genetic studies focus on populations of European ancestry, yet that group makes up just 18% of the global population.
While the field has become far better at acknowledging these knowledge and resource gaps, more needs to be done to close them. Each region has diseases that might be better understood by comparing ancient and modern DNA. Asgari points to sickle cell disease, which is believed to have arisen as a protection against malaria, or the high prevalence of diabetes in the Middle East, as areas that deserve the same kind of study.
There’s still so much to learn about the human genome. We’ll learn more, faster, if we cast a wider net.
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