DNA recovered from ancient human bones and teeth has revealed a remarkable evolutionary explanation for one of modern medicine’s mysteries. Genetic variants that today increase the risk of multiple sclerosis appear to have spread across Europe with Bronze Age herders around 5,000 years ago — possibly because those same genes once helped protect people against infectious disease.

Multiple sclerosis presents scientists with a puzzling geographical pattern.

The autoimmune disease, in which the immune system attacks the brain and spinal cord, is considerably more common in some populations than others.

Northern Europe has particularly high rates.

Why?

Part of the answer may lie not in modern Europe, but thousands of years in its past.

An international team involving scientists from the universities of Oxford, Cambridge, Copenhagen, Bristol and California, Berkeley analysed ancient human DNA to reconstruct how genetic variants associated with disease spread through European populations. Oxford University

Their findings revealed an extraordinary connection between prehistoric migration, infectious disease and multiple sclerosis.

DNA from Europe’s ancient inhabitants

The research was made possible by an enormous collection of ancient genetic material.

Scientists analysed DNA extracted from ancient bones and teeth preserved in museum collections across Europe and western Asia.

They then compared those ancient genomes with genetic information from modern populations, including the UK Biobank, which contains genetic and health information from around half a million participants. Oxford University

By doing so, researchers could effectively follow genetic variants through thousands of years of European history.

It is a form of genetic archaeology.

Instead of reconstructing migration only from pottery, weapons or burial sites, scientists can follow the movement of people through their DNA.

The Yamnaya arrive

One migration stood out.

Approximately 5,000 years ago, pastoralist herders associated with the Yamnaya culture moved westward from the Pontic Steppe — an enormous region covering parts of what are now Ukraine, southwestern Russia and western Kazakhstan.

They brought livestock.

They brought new cultural practices.

And they brought their genes.

The researchers found that Yamnaya ancestry contributed substantially to the genetic makeup of northern Europeans.

Crucially, the migrating population also carried genetic variants that today are associated with an increased risk of developing multiple sclerosis. Oxford University

Why would evolution preserve dangerous genes?

At first this creates another mystery.

If particular genetic variants increase the risk of a serious disease, why did natural selection not remove them?

The answer appears to depend on the environment.

The researchers argue that these variants probably provided an advantage to Bronze Age pastoralists.

Living closely with sheep, cattle and other domesticated animals exposed people to infectious diseases.

A more active immune system could therefore have been valuable.

Genetic variants capable of strengthening certain immune responses may have helped ancient populations survive infections. Oxford University

Thousands of years ago, that could have been an evolutionary advantage.

Today, the environment is very different.

The same immune system in a different world

Modern Europeans live with antibiotics, vaccines, improved sanitation and very different exposure to infectious diseases.

But our genomes still carry adaptations inherited from populations that lived under completely different conditions.

A genetic variant that once helped the immune system fight infection can therefore become problematic when that immune response is triggered in another context.

In multiple sclerosis, the immune system mistakenly attacks the body’s own nervous system.

Professor Lars Fugger of Oxford’s MRC Weatherall Institute of Molecular Medicine described the MS risk genes as effectively being “miscast” in the modern environment: their original biological role may once have been useful, while today’s circumstances are radically different. Oxford University

233 genetic risk variants

Multiple sclerosis does not have a single genetic cause.

Scientists have identified 233 genetic variants associated with MS risk.

The new research suggests that many of those variants may have been maintained because they historically provided protection against infectious diseases. Oxford University

That changes how scientists can think about the disease.

MS-associated genes are not necessarily genetic mistakes.

Some may instead be remnants of successful evolutionary adaptations.

The problem is that the environment in which those adaptations originally evolved no longer exists.

Evolution does not plan for the future

This illustrates an important principle of evolution.

Natural selection does not design organisms for conditions thousands of years in the future.

It favours characteristics that improve survival and reproduction under the conditions existing at the time.

A trait can therefore be beneficial in one environment and harmful in another.

The genes inherited from Bronze Age pastoralists demonstrate how strongly modern health can remain connected to ancient lifestyles.

Our immune systems did not originate in hospitals and modern cities.

They were shaped by migrations, animals, epidemics, food shortages and environments experienced by our ancestors over thousands of generations.

Four major prehistoric populations

The work formed part of a much larger effort to reconstruct the genetic history of western Eurasia.

The researchers used ancient genomes to investigate how major prehistoric populations contributed to present-day Europeans.

These included ancient hunter-gatherers, early farmers who migrated into Europe from Anatolia, and later steppe pastoralists such as the Yamnaya.

Different mixtures of these ancestral populations remain visible in European genomes today.

And those differences can influence susceptibility to disease.

The study therefore creates a bridge between archaeology and medicine.

Ancient migrations can help explain modern patterns of human health.

Ancient DNA becomes a medical tool

Ancient DNA research was once largely associated with questions such as:

Who were our ancestors?

Where did they migrate?

How were prehistoric populations related?

Those questions remain important.

But the technology is now beginning to answer another question:

Why do modern humans become ill?

By tracking disease-associated genes through time, researchers can investigate the evolutionary circumstances that caused particular variants to become common.

This could eventually help scientists understand not only multiple sclerosis but also other neurological, autoimmune and metabolic diseases.

The same research programme examined genetic influences associated with conditions including Alzheimer’s disease and type 2 diabetes. Oxford University

The past is still inside us

The Yamnaya migration occurred around five millennia ago.

Their settlements disappeared.

Their societies changed.

Their languages evolved.

But parts of their biology remain alive in millions of people.

That is perhaps the most striking lesson of the research.

Human evolution is not an abstract story confined to prehistory.

Its consequences are present inside our cells.

A genetic adaptation that may once have helped a Bronze Age herder survive exposure to pathogens carried by livestock can, thousands of years later, influence someone’s risk of developing an autoimmune disease.

Modern medicine is discovering that to understand the human body fully, sometimes we have to understand human history as well.

Source: Based on “Research into ancient DNA sheds new light on cause of Multiple Sclerosis and other neurodegenerative diseases,” published by the University of Oxford on 12 January 2024. The research involved scientists from Oxford, Cambridge, Copenhagen, Bristol and the University of California, Berkeley, and formed part of a series of studies published in Nature using a major ancient-DNA dataset.