Leprosy affected indigenous peoples across the Americas long before the first Europeans arrived. New genetic research reveals that leprosy was present millennia before Christopher Columbus crossed the Atlantic.
When the first Europeans arrived in the Americas, they brought many new diseases with them – including Mycobacterium leprae, the most well-known cause of leprosy.
But now, new research shows that another bacterium, Mycobacterium lepromatosis, had also ravaged the Americas for millennia – and still lurks in humans today. Without treatment, leprosy can cause chronic sores, numbness and severe nerve and tissue damage, and in the worst cases lead to amputation and social exclusion.
Historically, people with leprosy were often isolated from society, and the disease has been surrounded by fear and stigma for thousands of years.
“Today, there are still cases of leprosy caused by M. lepromatosis in the Americas, especially in Mexico. Our findings shed new light on how this bacterium spread across the Americas and Europe – and how it still lingers today in both humans and animals,” says Maria Lopopolo, a postdoctoral researcher from the Institut Pasteur in Paris, France.
Although leprosy is almost forgotten today, it still affects more than 200,000 people every year – especially in India, Brazil and Indonesia – and there are around 2,000 cases in the Americas alone.
The study has been published in Science.
Mysterious bacterium changes the known history of leprosy
For many years, it was believed that only M. leprae could cause leprosy. That changed in 2008, when M. lepromatosis was identified for the first time in Mexico.
Since then, several more cases have been found, but only now have researchers conducted the most comprehensive mapping of M. lepromatosis ever: the entire genome and comparing both modern and very old findings.
They discovered that M. lepromatosis has hardly changed over time and has very little genetic material – just like M. leprae.
This shows that both bacteria are extremely well adapted to their hosts and therefore difficult to eradicate.
“Until now, we have only had genomic data from three modern human-infecting strains and less than 10 animal-infecting strains of M. lepromatosis, which is a very limited dataset for such an organism,” explains Maria Lopopolo.
Traces of leprosy in 1,000-year-old skeletons
To determine the origins of M. lepromatosis, the researchers analysed hundreds of samples from both living people and Native American Ancestors’ archaeological material.
They found it in ancestors from Canada and Argentina, dated between 860 and 1,310 years ago, and used advanced ancient DNA techniques – methods for extracting and reading old DNA – to reconstruct its genetic material.
They then combined the ancient findings with modern samples to track the evolution of M. lepromatosis over millennia and draw a detailed genetic family tree showing the relationship between different samples and how it spread across the Americas.
The researchers used ancient DNA sequencing and contamination control, reconstructed entire genomes (the total genetic material of organisms)and compared them with existing databases for M. leprae and related mycobacteria.
A genetic timeline of a forgotten disease
The combination of ancient DNA and modern data provided, for the first time, a broad genetic overview of M. lepromatosis across time and geography, enabling researchers to construct a phylogeny – a genetic family tree showing how the bacteria are related and evolved from common ancestors.
The modern samples were collected and processed over a period of four years with the help of leprosy experts and clinicians at hospitals in the Americas, including the Caribbean, and the historical samples were collected with the help of local researchers and indigenous people from different parts of the Americas, from the southernmost part of Patagonia in Argentina to the northernmost part of British Columbia in Canada.
Based on the results, the researchers drew up a complete family tree for M. lepromatosis and placed old finds from the Americas in it.
“This research could not have been carried out without the help of local indigenous peoples throughout the Americas and leading experts in the field. With this study, we are mapping M. lepromatosis leprosy in the Americas before European ships arrived,” says Maria Lopopolo.
Spread throughout the Americas long before the Europeans arrived
So what does the mapping of the M. lepromatosis genome show?
M. lepromatosis leprosy was present from Argentina in the south to Canada in the north before Europeans sailed across the Atlantic more than 1,000 years ago.
Nevertheless, the related bacterium M. leprae, which arrived on European ships in the 16th century, later became the most widespread cause of leprosy in the Americas.
The researchers found five genetic lineages of M. lepromatosis.
One lineage originated nearly 10,000 years ago and is still found in humans today, especially in North America – suggesting that M. lepromatosis was once more diverse than previously thought and that unknown variants may still exist.
Further, ancient bacteria from both North and South America are surprisingly closely related, even though they had lived thousands of kilometres apart.
The findings suggest that M. lepromatosis spread rapidly across the Americas – perhaps within just a few centuries.
From the Americas to red squirrels in Europe
One bacterial lineage was previously found in red squirrels in the United Kingdom and Ireland by Dr Charlotte Avanzi in 2016 and co-author of this new study.
Genetic analyses show that it most likely originated from an ancestor that lived in the Americas more than 3,500 years ago when there were no contacts between the Americas and Europe and was probably brought to Europe in the 1800s.
The researchers used molecular clock analysis – a method that uses genetic mutations as a biological timekeeper to calculate when species evolved from a common ancestor – and revised the timeline for when M. leprae and M. lepromatosis diverged from a common ancestor.
The researchers showed that M. lepromatosis and M. leprae are much more closely related than previously thought.
Leprosy older than humans – but still not eradicated
The two bacteria are now thought to have diverged from a common ancestor between about 2 million and 700,000 years ago, close to the time when humans originated.
“This discovery changes understanding of disease dynamics in the Americas. The story of epidemics in the wake of colonisation is not wrong – many disease-causing bacteria were indeed introduced after 1492, including leprosy, but the history of leprosy begins earlier than previously thought,” says Maria Lopopolo.
“The fact that M. lepromatosis was endemic in both North and South America before Europeans arrived means that indigenous populations were already living with chronic mycobacterial disease, which had potential social and demographic consequences.”
The World Health Organization continues to work to eradicate leprosy, but it survives mainly among the world’s poorest and most marginalised populations, in which lack of treatment can lead to chronic wounds, numbness, severe nerve and tissue damage and, in the worst cases, amputation and social exclusion.
The new discovery provides researchers with important knowledge about how leprosy has survived in small pockets for millennia – and how it can still be kept in check and perhaps one day eradicated completely.
