Our Ancestral DNA Tells Us Who We Are!

Human history is written in our ancestral DNA. Our ancestral DNA tells us where they lived, how they resisted disease, with whom they mixed and how they migrated. It also determines who we are today and where we come from. It also carries clues to the health problems we may face in the future. Our ancestral DNA is the subject of groundbreaking research that provides detailed insights into prehistoric human diversity and migration.

Four groundbreaking research articles, featured in Nature, delve into the intricate genetic imprints and geographical origins of human diseases, offering detailed insights into prehistoric human diversity and migration. The studies also put forth a compelling explanation for the increased genetic susceptibility to multiple sclerosis (MS).

Utilizing data from the most extensive dataset to date, encompassing 5,000 ancient human genomes from Europe and Western Asia (Eurasia), the research unveils the prehistoric human gene pools of western Eurasia with unparalleled precision.

The collaborative effort behind these findings involves an international team led by experts from the University of Copenhagen, with contributions from approximately 175 researchers hailing from universities and museums across the globe. This diverse group represents a broad spectrum of scientific disciplines, including archaeology, evolutionary biology, medicine, ancient DNA research, infectious disease research, and epidemiology. Researchers from the U.K., the U.S., Germany, Australia, Sweden, Denmark, Norway, France, Poland, Switzerland, Armenia, Ukraine, Russia, Kazakhstan, and Italy have collectively contributed to these pioneering studies.

The research findings unveiled in the Nature articles stem from a detailed analysis of a subset of 5,000 genomes, highlighting several key discoveries:

1. Cultural barriers in ancient Europe: The study underscores the profound genetic implications of a culturally determined barrier that persisted until around 4,000 years ago, stretching from the Black Sea in the south to the Baltic Sea in the north across Europe.
2. Dispersal of risk genes: The research maps out the dispersion of risk genes associated with various diseases, including type 2 diabetes and Alzheimer’s disease, following significant migration events over 5,000 years ago in Eurasia.
3. Multiple sclerosis in scandinavia: The articles present compelling scientific evidence of ancient migrations shedding light on the puzzling observation that the prevalence of multiple sclerosis is twice as high in Scandinavia compared to Southern Europe.
4. Population turnovers in Denmark: The analysis reveals the mapping of two nearly complete population turnovers within Denmark, occurring within a single millennium. This provides unprecedented insights into the dynamic demographic shifts in the region.

The project of 5,000 ancient human genomes

The extensive dataset comprising 5,000 ancient human genomes was meticulously reconstructed through the analysis of bones and teeth, made accessible through a collaborative scientific effort involving museums and universities spanning Europe and western Asia. This significant sequencing endeavor was made possible by leveraging the capabilities of Illumina technology.

Spanning various historical periods, from the Mesolithic and Neolithic to the Bronze Age, Iron Age, Viking period, and into the Middle Ages, the age of specimens within the dataset offers a comprehensive temporal panorama. Notably, the oldest genome in this collection is derived from an individual who lived around 34,000 years ago.

The genesis of the ancient human genomes project, conceived in 2018 by three University of Copenhagen professors, aimed to reconstruct 1,000 ancient human genomes from Eurasia as a pioneering tool for precision research in brain disorders. The architects of this project include Eske Willerslev, an expert in ancient DNA analysis and project director; Thomas Werge, an authority on genetic factors associated with mental disorders, and head of the Institute of Biological Psychiatry serving Mental Health Services in the Capital Region of Denmark; and Rasmus Nielsen, a specialist in statistical and computational analyses of ancient DNA, affiliated with the University of California, Berkeley in the U.S. This collaborative effort marked a significant step in advancing our understanding of human genomic history.

The primary goal was to curate an unparalleled ancient genomic dataset to explore the genetic traces and evolutionary history of brain disorders, offering novel insights into these conditions across extensive periods. This ambitious objective involved cross-disciplinary comparisons between ancient DNA profiles and data from various scientific fields.

Identifying neurological conditions such as Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis, alongside mental disorders like ADHD and schizophrenia, as potential subjects, three professors initiated the project. Seeking financial support, they approached the Lundbeck Foundation, a prominent Danish research foundation, in 2018. The foundation granted a substantial five-year research fund amounting to DKK 60 million (approximately EUR 8 million) for the initiative. The University of Copenhagen took charge of coordinating the project through the newly established Lundbeck Foundation GeoGenetics Center.

The significance of this generous funding lies in its potential to pioneer a profound understanding of the evolving genetic architecture behind brain disorders over time. Jan Egebjerg, Director of Research at the Lundbeck Foundation, underscores that brain disorders represent the specific focus area of this groundbreaking project, justifying the substantial research grant awarded in 2018.

The Lundbeck Foundation extends its support to the iPYSCH consortium, a globally significant initiative investigating the genetic and environmental underpinnings of mental disorders. These disorders include autism, ADHD, schizophrenia, bipolar disorder, and depression, with a primary emphasis on refining the precision of genetic risk profiles associated with these conditions.

The findings reported in Nature draw strength from a rigorous validation process. This involves a meticulous comparison of the ancient genomic dataset with de-identified genetic data sourced from the expansive Danish iPYSCH consortium. Additionally, DNA profiles from a cohort of 400,000 contemporary individuals, meticulously cataloged in the UK Biobank, contribute to the robust validation of the reported results. The collaborative effort underscores the comprehensive approach undertaken to illuminate the intricate interplay between genetic and environmental factors in mental health disorders.

Numerous hurdles to overcome

The project’s inception was experimental, driven by the curiosity to unravel insights into the environmental factors shaping the evolution of diseases and disorders, recounts Professor Werge. The initial aim was to gather ancient human specimens, exploring the potential revelations hidden within them. The project, however, evolved into a vast, complex undertaking, ultimately leading to its unique distinction of being described in four articles by Nature.

Professor Willerslev highlights the significant logistical hurdles faced in compiling the DNA dataset. The project required access to archaeological specimens, specifically human teeth and bones scattered across museums and institutions in the Eurasian region. Overcoming this challenge involved establishing numerous collaboration agreements. Once in place, the project gained momentum, resulting in a booming dataset that now comprises over 5,000 ancient human genomes. The substantial size of the dataset has markedly improved both the usability and precision of the research outcomes.

Professor Nielsen took charge of planning the statistical and bioinformatics analyses conducted on the information extracted from ancient teeth and bones within the laboratories at the University of Copenhagen. Navigating through an extensive volume of data, he grappled with the intricacies of severely degraded DNA, showcasing the project’s dedication to overcoming obstacles and extracting valuable insights.

Analyzing an unprecedented number of ancient genomes presented a unique challenge, as no one had previously tackled such extensive genetic data. The complexity arose from the intricate nature of raw data, which consisted of numerous short DNA sequences with inherent errors. Moreover, these sequences needed accurate mapping to their respective positions in the human genome. Complicating matters further was the potential for contamination from microorganisms residing on ancient teeth and bones.

To illustrate the complexity of the task, envision a jigsaw puzzle with millions of pieces, all mixed up with fragments from four other incomplete puzzle sets, subjected to an hour-long run in the dishwasher. Reassembling this genetic puzzle proved to be an intricate undertaking. Professor Nielsen emphasized that a crucial factor in their ultimate success was collaboration with Dr. Olivier Delanau from the University of Lausanne. Dr. Delanau’s expertise in developing algorithms played a pivotal role in overcoming the challenges posed by the complex data, ensuring the accurate reconstruction of the genetic puzzle.

Global attention

Reports of a comprehensive compilation of a substantial ancient human genome dataset quickly circulated within scientific circles, sparking heightened interest since 2022, as noted by Professors Werge, Willerslev, and Nielsen. The trio highlights the continuous influx of inquiries from researchers worldwide, particularly those focused on diseases, seeking access to explore the rich ancient DNA dataset.

The significance of the four Nature articles lies in their demonstration of the 5,000-genome dataset as a precise instrument capable of yielding novel insights into diseases. By integrating analyses of present-day human DNA data and leveraging inputs from various research fields, this large dataset becomes a versatile tool with immense potential for disease research.

Professor Willerslev emphasizes the remarkable scope of applications that such an extensive ancient genomic dataset can offer within disease research. The anticipation is that, as fresh scientific revelations derived from the 5,000-genome dataset emerge, more data will progressively become freely accessible to researchers. The ultimate goal is to make the complete dataset open access, ensuring universal availability for researchers across diverse scientific disciplines.

In summary, this study uses a large dataset of 5,000 ancient prehistoric human genomes to reveal new insights into humanity’s disease history, culture and heritage. This dataset is the result of a collaborative project by researchers from around the world. By examining the relationships between our ancestral DNA and modern human DNA, researchers have gained new insights into the origin, spread and impact of disease. This work was published in Nature in four papers that show how our ancestral DNA can be used in disease research. These papers proved that ancestral DNA is a versatile and sensitive tool in disease research. As a result of the research, the dataset is planned to be made open access for researchers who want to learn more about our ancestral DNA. This will make it possible to make more scientific discoveries about our ancestral DNA.

Resources

1. ^{ONLINE NEWS} University of Copenhagen. (2024, January 13). Discoveries gleaned from ancient human DNA. Phys.org. [Phys.org]
2. ^JOURNAL Allentoft, M.E., Sikora, M., Refoyo-Martínez, A., et al. (2024). Population genomics of post-glacial western Eurasia. Nature, 625, 301–311. [Nature]
3. ^JOURNAL Irving-Pease, E. K., Refoyo-Martínez, A., Barrie, W., et al. (2024). The selection landscape and genetic legacy of ancient Eurasians. Nature, 625, 312–320. [Nature]
4. ^JOURNAL Barrie, W., Yang, Y., Irving-Pease, E.K. et al. (2024). Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations. Nature, 625(7899), 321–328. [Nature]
5. ^JOURNAL Allentoft, M. E., Sikora, M., Fischer, A., et al. (2024). 100 ancient genomes show repeated population turnovers in Neolithic Denmark. Nature, 625(7898), 329–337. [Nature]

Cite this page: