Ancient Immunity: The Role of Archaic Genes in First Nations Peoples of Oceania

Denisovan Genetic Legacy and its Impact on Immunity in First Nations Oceanians

A new study in Cell¹ has revealed that an ancient gene variant in the First Nations inhabitants of Oceania, inherited from Denisovans, could influence their immune response. The allele, known as KIR3DLI*114, is widespread across populations in Australia, New Guinea, the Solomon Islands, and other regions of Oceania. Researchers believe it may have once provided protective benefits but could now contribute to modern health disparities.

Denisovan Legacy and the Origins of the KIR3DLI*114 Allele

Denisovans were a group of archaic humans who diverged from Homo sapiens after migrating out of Africa. As First Nations peoples of Oceania moved through Eurasia, interbreeding with Denisovans introduced genetic material that still affects these populations today. Scientists traced the KIR3DLI*114 allele back to this ancient group, noting that it is unique to Oceania.

Lead researcher Paul Norman, Ph.D., from the University of Colorado, states,

“We found a diverse set of genes, but this allele stood out due to its distinct composition and possible Denisovan origin.”

This gene variant is particularly notable in its connection to the immune system and its potential role in susceptibility to infectious diseases like influenza.

Immune Function and Health Implications

The study highlights that KIR3DLI*114 might have once offered immunological advantages, aiding in the survival of early Oceanians. However, today, this ancient gene could make some First Nations individuals more vulnerable to infections. The researchers tested the impact of this allele on natural killer (NK) cells, crucial components of the immune system, which may contribute to the heightened response to diseases seen in some Oceanian populations. Norman said,

“The allele likely provided protection in ancient times, but we suspect that it now contributes to susceptibility in modern contexts.”

The findings indicate that up to 30% of First Nations individuals across Oceania carry this gene variant, impacting millions.

Understanding the Immune Evolution of First Nations Peoples

The unique KIR3DLI*114 allele is just one example of how ancient human interbreeding has left a genetic footprint on modern populations. By examining the distribution and function of this allele, researchers hope to better understand the immune systems of these populations. The study holds far-reaching implications for the treatment of diseases, especially those affecting innate and adaptive immunity. Norman emphasized,

“This study is a breakthrough in demonstrating the functional role of archaic genes in modern populations. It showcases how these genetic remnants of our evolutionary past continue to influence the health of descendants today.”

Conclusion: Addressing Modern Health Challenges

The research brings attention to the health disparities faced by First Nations peoples of Oceania. By tracing the genetic influences of ancient interbreeding events, scientists are building a clearer picture of how genetics can contribute to both resilience and vulnerability in human populations.

Moving forward, the study’s findings are likely to influence research on autoimmune diseases, cancer, and infectious disease treatments. As Norman concludes, “We are using these methods to address health disparities and provide better care to populations today.” The collaborative nature of this study—spanning institutions in Australia, the UK, and Papua New Guinea—underscores its global importance.

1. Loh, L., Saunders, P. M., Faoro, C., Font-Porterias, N., Nemat-Gorgani, N., Harrison, G. F., Sadeeq, S., Hensen, L., Wong, S. C., Widjaja, J., Clemens, E. B., Zhu, S., Kichula, K. M., Tao, S., Zhu, F., Montero-Martin, G., Fernandez-Vina, M., Guethlein, L. A., Vivian, J. P., … Norman, P. J. (2024). An archaic HLA class I receptor allele diversifies natural killer cell-driven immunity in First Nations peoples of Oceania. Cell. https://doi.org/10.1016/j.cell.2024.10.005