Tyrolean Iceman's Genome Unveils Surprising Ancestry and Baldness Clue

A collaborative team of scientists has reanalyzed the genome of “Ötzi”, one of the oldest human glacier mummies. Their data, published in Cell Genomics, reveals new, “surprising” insights into Ötzi’s ancestry and physical characteristics, including the fact he was likely experiencing male-pattern baldness and had a “healthy” lifestyle.

Meet Ötzi, the “Ice Man”

Ötzi’s remains were uncovered in the Ötzal Alps, a mountain range in the Central Eastern Alps, in 1991. Using radiocarbon dating, scientists determined that he lived in the Italian portion of the Alps approximately 3350–3210 years BCE.

Over the last decade, advances in DNA extraction tools and next-generation sequencing technologies have enabled scientists across the globe to sequence DNA extracted from ancient specimens. This process faces numerous challenges; ancient DNA is often heavily degraded, making it difficult to “piece together” individual chunks to achieve a full genome. Modern-day human or environmental DNA can also contaminate the specimen through handling and processing, potentially skewing the results.

In 2012, a team led by Professor Andreas Keller, chair for clinical bioinformatics at Saarland University in Germany, sequenced Ötzi’s genome. While their data revealed interesting insights into the iceman’s history – suggesting he was closely related to Steppe Herders – the genome had relatively low coverage. What’s more, at the time of the study, there was less human genome data than exists today to compare Ötzi’s DNA against his contemporaries.

“In 2012 there were different sequencing platforms available and the sequencing depth (number or DNA reads) was much lower than today,” says anthropologist Professor Albert Zink, head of the Institute for Mummy Studies at Eurac Research in Bolzano, Italy.

Professor Johannes Krause of the Max Planck Institute for Evolutionary Anthropology in Leipzig, and colleagues – in collaboration with Zink – saw an opportunity to reanalyze Ötzi’s genome. “For the new study we used a sequencing platform that has become the standard for ancient DNA studies. It allows us to generate high-coverage genomes and thereby much better data and a more accurate data analysis,” Zink describes.

Ötzi’s ancestors arrived directly from Anatolia

Contemporary European populations possess a genetic composition formed through the blending of three fundamental ancestral groups. We owe this knowledge to the analysis of ancient genomes, Zink emphasizes: “It helps to understand the different migration patterns that have shaped the genetic composition of modern populations. For example, we know now that the Neolithic farmers arrived in Europe around 8000 years ago and replaced the previous hunter-gatherers by admixture. Later, at around 5000 years ago, people from Eurasia (Steppe) arrived in Europe and mixed with the farmers.” 

In conflict with the 2012 analysis, the researchers found no evidence of Steppe-related ancestry in Ötzi’s genome. “We were very surprised to find no traces of Eastern European Steppe Herders in the most recent analysis of the Iceman genome; the proportion of hunter-gatherer genes in Ötzi’s genome is also very low,” says Krause. The team believes that the inaccuracy stems from modern DNA contamination in the study by Keller et al: “Contamination estimates showed that the high-coverage genome is almost free of contamination, in contrast to the previous genome showing around 7% of human DNA contamination,” they write.

Comparing Ötzi’s genome to that of his prehistoric European contemporaries revealed that the largest proportion of his DNA comes from early Neolithic Anatolia farmer-related ancestry. This finding implies that these individuals were isolated from other Europeans who mixed more with ancient European hunter-gatherers, perhaps due to the remote location of the Alps. “Genetically, his ancestors seem to have arrived directly from Anatolia without mixing with hunter-gatherer groups,” Krause says. Today, Anatolia constitutes a large portion of Turkey.   

Ötzi had dark skin, was potentially bald and ate a Mediterranean diet

Beyond his genetic ancestry, Krause and colleagues were able to piece together a picture of Ötzi’s phenotype – what he looked like, his lifestyle and whether he was at risk – genetically – for human diseases.

Ötzi’s skin type had been previously determined as Mediterranean-European, but the high-quality genome suggests his skin color may have been darker. “Skin color is genetically determined by a high number of genetic regions. This allows a fairly accurate determination of the skin color in ancient human remains. Our analysis has shown that his skin color was very dark, darker than today’s South Europeans, such as in Sicily or Andalusia, but less dark than in Sub-Saharan Africans,” Zink explains. It had been assumed that Ötzi’s darker skin color – clearly visible in images of the mummified ice man – was a result of the preservation processes that occurred while he was frozen in ice. The genetic data contradicts this, suggesting that the skin color we see in images of Ötzi today is his original skin color.

The Tyrolean Iceman is known as one of the oldest human glacier mummies CREDIT Südtiroler Archäologiemuseum EURAC Marco Samadelli-Gregor Staschitz. Credit: Südtiroler Archäologiemuseum/EURAC/Marco Samadelli-Gregor Staschitz.

Ötzi’s genome also suggests he was predisposed to male-pattern baldness, which may explain why almost no hair was found on his remains. From a disease standpoint, genetic variants associated with a higher risk of diabetes were uncovered, but the researchers believe his “healthy lifestyle” – Ötzi carried gene variants associated with consumption of a Mediterranean diet – may have offset this risk. “We know that Ötzi had a ‘healthy’ lifestyle, at least according to modern standards, as he was very active (we can see on his body that he was walking a lot and had a well-trained body), he was not overweight, he wasn’t smoking (although may have inhaled some campfire smoke) and had a well-balanced diet,” says Zink. “The latter was proven by stable isotope analysis and our analysis of his stomach contents.”

Ongoing studies compare Ötzi’s genome to local contemporaries

The work by Krause and team adds to a growing body of ancient DNA analysis literature, a field that Zink views as highly beneficial for modern-day humans. Beyond reconstructing our history, ancient DNA “helps us to detect infectious diseases, such as tuberculosis, leprosy, plague, etc., and thereby learn about their occurrence, transmission and evolution,” he says. Equipped with this knowledge, we might be able to find better ways to treat and prevent these diseases today.

Ötzi’s time in the limelight is far from over. The research team are analyzing skeletal findings from South Tyrol and Trentino, two regions in the North of Italy, to gain a broader understanding of the populations present at that time. They want to know whether Ötzi – who is just one individual after all – is representative of his contemporaries. “The analyses are not yet finished, but should be ready within the next year,” Zink hints.

Professor Albert Zink was speaking to Molly Campbell, Senior Science Writer for Technology Networks.

Reference: Wang K, Prufer K, Krause-Kyora B, et al. High-coverage genome of the Tyrolean Iceman reveals unusually high Anatolian farmer ancestry. Cell Press. 2023. doi: 10.1016/j.xgen.2023.100377