The Diverse Applications of Ancient DNA Research

For many, the idea of ancient DNA (aDNA) can invoke images from the iconic movie scene with a mosquito trapped in amber, or perhaps one of the real discoveries involving a woolly mammoth perfectly preserved in ice¹. However, this field is much more than unearthing prehistoric animals or a real project working to resurrect them². The study of aDNA is vital for interpreting the past and making sense of the present. For example, Swedish geneticist Svante Pääbo won the Nobel Prize in 2022 for his research involving DNA from Neanderthals³. Interestingly, the specific work that won him the award revealed how a genomic segment inherited from Neanderthals is an important genetic risk factor for severe symptoms post-SARS-CoV-2 infection⁴.

Broad Applications
While Pääbo’s research is a renowned example, the study of aDNA encompasses a range of thrilling discoveries spanning numerous fields. “I think ancient DNA has applications in understanding human disease, how we adapt to pathogens, how we adapt to culture, and how humans adapt to different ecologies,” explained John Lindo, J.D., Ph.D., Assistant Professor at Emory University. His lab is one of the leading groups in the aDNA field, and they’ve excelled in both the wet lab and computational side of this complex process.

Lindo’s work also captures the broad scope of aDNA research by uncovering important information about human culture, adaptations to diverse environments, and the impacts of historical interactions. Lindo shared that his group’s research has three overarching themes:

1. Understanding the evolutionary histories of the people of the Americas, which includes ancient migration routes, discovering ancestral lineages, and understanding how they adapted to the many ecologies and cultures of the Americas.

2. Reconnecting Latine populations in the United States with their Indigenous ancestries, before European contact, via local ancient DNA studies throughout Meso and South America.

3. Understanding the biological effects of European colonization on the Indigenous people of the Americas.

Some of Lindo's recent collaborations have helped to reshape our understanding of Indigenous genetic history in South America⁵, offering insights beyond what traditional archaeological methods could achieve. Another study Lindo contributed to revealed a unique ancient lineage of the Blackfoot people in North America⁶. A surge in aDNA research has been crucial in tracing the history of our ancestors across Europe⁷, Africa⁸, or the Americas⁹, spanning hundreds to thousands of years.

Other unique aDNA studies have illustrated the diversity of social and health conditions in historical contexts, such as during the Black Death era¹⁰. Reconstructed oral microbiomes of human populations post-plague highlighted the health and dietary habits of those who lived through one of history's most devastating pandemics¹¹.

This research significantly contributes to filling the historical gaps in our knowledge of humanity, and can also lead to unexpected discoveries as Lindo pointed out. “I’m always surprised by the results of genomic scans that look for positive selection in an ancient population,” he stated. “For example, when we scanned an ancient population from a high-altitude Andean archeological site, we were expecting the strongest signals to be related to adaptation to hypoxia. Instead, the strongest signal was related to starch digestion and could correlate with the local agriculture in the region that focused on starchy plant foods, which included the domestication of the potato.”

Ecosystems and Beyond
Outside of human research, aDNA studies have given significant insights into the landscape of ancient environments, some dating back over two million years¹². These approaches have been pivotal in various animal studies. For instance, it has played an important role in establishing timelines for the domestication of animals¹³, which is a key aspect of understanding human-animal relationships throughout history. Investigations involving the aDNA of animals such as North American bison show ancient bison migration patterns, their evolutionary history, and the ecological impact on North America's prehistoric landscape and biodiversity¹⁴. Moreover, research focused on ancient chickens was instrumental in uncovering the origins of a troubling pathogens' virulence¹⁵.

Similarly in plants, this type of work has been equally important by giving researchers a snapshot of the various plant communities and how they’ve changed over time¹⁶. Even ancient plant DNA taken from a 2,900-year-old clay brick can tell us about ancient biodiversity and how much of this biodiversity was lost over the years¹⁷.

These innovative studies underscore the diverse impact of aDNA research in both human history and the natural world.

Challenges and Innovations
As one can imagine, the process of extracting and analyzing DNA from centuries-old remains is no easy task, yet Lindo emphasized a more significant hurdle. “The first key challenge is the ethical treatment of the samples and the recognition of stakeholders, which is not always obvious,” he stated. The complexity of this issue has led many in the field to create guidelines¹⁸ and maintain ongoing conversations¹⁹ that focus on ethical conduct and respect in aDNA research. This involves considering stakeholder engagement, informed consent, and cultural sensitivity, especially when studying DNA from Indigenous and ancestral groups.

The second, more obvious challenge in aDNA research is technical. Lindo noted that “most samples are highly degraded and carry little endogenous DNA. This is especially a concern when a precious few samples exist from important archeological sites.” In recent years, several developments have greatly assisted with this process. Particularly, new DNA extraction strategies have emerged that boost recovery rates and minimize damage to irreplaceable samples²⁰. Contemporary approaches for the analyses also help overcome the challenges of analyzing small DNA fragments and identifying environmental contamination²¹.

In addition to these advancements, Lindo shared that next-generation sequencing (NGS) has revolutionized the field. “Before this advancement, ancient DNA was mostly dominated by mitochondrial DNA demographic studies,” he added. It’s no coincidence that shortly after next-generation sequencers came onto the market, the first ancient human genome was produced²². The introduction of NGS has also led to an explosion in publications centered on aDNA discoveries. This progression of sequencing technologies and analysis methods will continually improve the depth and accuracy of aDNA research.

“I think ancient DNA is still in its infancy, with most of the work being done on European populations,” shared Lindo. “There is much about human prehistory that is poorly understood, and I think ancient DNA can help us build a comprehensive picture of our ancestors, in terms of understanding our own evolutionary histories.” As more diverse populations are studied, the potential for this research to shed light on previously unexplored aspects of human history is immense.


References

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