Ancient DNA (aDNA) is DNA that has been extracted from extremely old (560,000-780,000 year old [Orlando et al, 2021]) samples such as wood, bones, sediments, or paleofeces. While aDNA might bring to mind Jurassic Park-type science, many real-life scientists work with aDNA to understand the genetic diversity of prehistoric life and to elucidate how organisms that live today have evolved.
This post provides a general overview into the world of aDNA, what it is, how it is analyzed, and what it can tell us.
What is aDNA?
aDNA is obtained from ancient samples, meaning that these DNA molecules originate from organisms that lived up to 1.65 million years ago (van der Valk et al, 2021). Obtaining aDNA is a high stakes risk for researchers because they have to extract it from samples that are irreplaceable, meaning that sample extraction and preparation must be done with great care.
Common samples for aDNA extraction include materials such as wood, sediments, parchments, textiles, hair, bones, teeth, paleofeces, and even dental plaque. The latter two types are particularly interesting because they allow researchers to obtain information about what the ancient intestinal and oral microbiome may have looked like (Orlando et al, 2021). This is discussed in further detail later.
How is aDNA analyzed?
Because of the unique nature of the samples that contain aDNA, researchers have to consider both ethical and scientific questions when deciding how/if to proceed with DNA extraction. If a sample is cleared to be processed, the aDNA that is obtained from it is usually highly degraded and contaminated with DNA present from the surrounding environment. Further, because the DNA is coming from a sample of a long-dead organism, there are different types of chemical changes that have occurred to the molecule which researchers have to ‘remove’ or correct for.
All of these factors make the following steps in a research workflow tricky. The steps that ‘correct’ the chemical changes made to the molecules make the actual sequencing of the aDNA more efficient and less prone to errors. However, by making these corrections, scientists also run the risk of biasing their sequencing results and therefore their conclusions. If you want to know more, the steps of this correction are outlined in a Nature review paper published in 2021 by Orlando et al.
After this optional correction step, aDNA is then prepared into what is called a DNA library. This is a collection of prepared (extracted, corrected, cleaned) DNA molecules that have all of the necessary components for sequencing and downstream computational analysis. Different methods can be used to generate DNA libraries depending on the goal of the research study.
After the library preparation step, the library is sequenced using a next generation sequencing technology (e.g., Illumina, Pacbio). Once the sequencing step is completed, the generated data are computationally analyzed.
What can aDNA tell us?
The information held within aDNA is considered invaluable as it can help answer critical evolutionary questions and provide key insights into ancient pathogens and host-associated microbiomes.
For example, using the methods described above, researchers have gained access to the genetic information of strains of historically important pathogens such as the 1918 influenza virus and Yersinia pestis (commonly known as plague). Some of these pathogens (e.g., the flu virus) are still actively circulating, but luckily the historical strains that caused pandemics are no longer around.
...aDNA has provided researchers with important information about these pathogens such as how they were able to spread so quickly and their long-term biological impacts.
This also means that these strains were not preserved in a laboratory so researchers have little insights into why these microbes were so deadly. However, aDNA has provided researchers with important information about these pathogens such as how they were able to spread so quickly and their long-term biological impacts (Patrono et al, 2022; Immel et al, 2021).
Comparison of the intestinal and oral microbiomes of ancient and modern day humans has also uncovered exciting information. For example, we know from paleofecal samples that the ancient intestinal microbiome was more diverse than the intestinal microbiome of humans alive today (Tito et al, 2008). Ancient dental plaque has also allowed researchers to gain important insights into how the development of agriculture impacted the host microbiome (Quagliariello et al, 2022). Taken together, these and similar studies are helping us understand how the communities of microbes living in our intestines and in our mouths have changed through time, and have helped us adapt to the world around us.
Conclusions
Whether or not aDNA will be the key to resurrecting the long extinct species of dinosaurs has yet to be seen. However, what is clear is that current research using aDNA can help researchers peek into the past by providing access to the historically important pathogens (Immel et al, 2021; Patrono et al, 2022), ancient host-associated microbes (Tito et al, 2008; Quagliariello et al, 2022), and even the ancient human genome (Orlando et al, 2021; Narasimhan et al, 2019).
This knowledge can help us understand how certain infectious diseases behave and make predictions on how emerging diseases might spread in the future. Further, aDNA can help us unravel how ancient humans lived and migrated, ultimately providing the foundations for who we are today.
Reference:
Orlando, L., Allaby, R., Skoglund, P. et al. Ancient DNA analysis. Nat Rev Methods Primers 1, 14 (2021). https://doi.org/10.1038/s43586-020-00011-0
Patrono, L.V., Vrancken, B., Budt, M. et al. Archival influenza virus genomes from Europe reveal genomic variability during the 1918 pandemic. Nat Commun 13, 2314 (2022). https://doi.org/10.1038/s41467-022-29614-9.
Immel, A., Key, F.M., Szolek, A., et al. Analysis of Genomic DNA from Medieval Plague Victims Suggests Long-Term Effect of Yersinia pestis on Human Immunity Genes. Mol Biol Evol. (2021). https://doi:10.1093/molbev/msab147.
Tito, R.Y., Macmil, S., Wiley, G. et al. Phylotyping and Functional Analysis of Two Ancient Human Microbiomes. PLOS One (2008). https://doi.org/10.1371/journal.pone.0003703
Quagliariello, A., Modi, A., Innocenti, G. et al. Ancient oral microbiomes support gradual Neolithic dietary shifts towards agriculture. Nat Commun 13, 6927 (2022). https://doi.org/10.1038/s41467-022-34416-0
Narasimhan, V.M., Patterson, N.; Moorjani, P., et al. The formation of human populations in South and Central Asia. Science (2019).
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