Recent findings from a comprehensive genetic study have significantly altered our understanding of the ancestry of the Japanese people. By examining the complete genomes of over 3,200 individuals from various regions across Japan, researchers have uncovered that the population is not merely derived from two ancestral groups, as previously believed, but rather from three distinct groups.
This groundbreaking study, conducted by scientists at RIKEN’s Center for Integrative Medical Sciences, provides compelling evidence that the modern Japanese population descends from not just the Jomon hunter-gatherers and East Asian rice-farming migrants, but also a lesser-known group known as the Emishi, originating from northeast Asia. This revelation supports the theory that the genetic heritage of Japan is far more complex and diverse than previously thought.
Chikashi Terao, the lead researcher of the study, emphasizes, “The Japanese population isn’t as genetically homogenous as many assume. Our analysis revealed Japan’s subpopulation structure on a fine scale, beautifully classified according to geographical locations in the country.”
To unveil these complex threads of ancestry, the research team employed whole-genome sequencing, a cutting-edge technique that deciphers all 3 billion base pairs of DNA. This method, which is significantly more informative than traditional DNA microarray techniques, allowed for an unprecedented examination of genetic diversity within Japan. The study spans seven regions, from the northernmost island of Hokkaido to the southern shores of Okinawa, making it one of the largest genomic studies conducted on a non-European population.
“Whole-genome sequencing provides us with a wealth of data, enabling us to discover more intriguing findings,” Terao states. This level of detail has offered insights into how Japan's ancestry is shaped by geographic factors.
In order to explore the connections between genetic data and specific diseases, Terao and his team integrated the genomic information with clinical data, including disease diagnoses and medical histories. This compilation led to the creation of a valuable resource known as the Japanese Encyclopedia of Whole-Genome/Exome Sequencing Library (JEWEL).
The examination of rare gene variants was a focal point of the study. Terao noted, “We postulated that rare variants could be linked to specific ancestral populations, providing insights into migration patterns within Japan.” Their hypothesis was confirmed, revealing that Jomon ancestry is most prevalent in southern Okinawa, while it diminishes in western regions. Conversely, the genetic makeup of western Japan exhibits a closer affinity to Han Chinese ancestry, likely a result of migration patterns from East Asia between 250 and 794 AD.
The research team also investigated the presence of genes inherited from archaic humans, such as Neanderthals and Denisovans, which have interbred with modern humans. Terao expressed interest in understanding why certain ancient genomes persist in contemporary DNA sequences, as these genes are often associated with specific traits or health conditions. For instance, genes inherited from Denisovans in Tibetan populations have been linked to adaptations for high-altitude living.
The study identified 44 ancient DNA regions present in modern Japanese individuals, most of which are unique to East Asians. Notably, a Denisovan-derived segment within the NKX6-1 gene has been associated with type 2 diabetes, potentially influencing responses to medications such as semaglutide. Furthermore, 11 Neanderthal-derived segments were linked to various health conditions, including coronary artery disease and rheumatoid arthritis.
The findings from this extensive genetic research have implications for the future of personalized medicine. By analyzing rare genetic variants, the researchers identified a variant in the PTPRD gene that may significantly impact health, linking it to hypertension and other serious conditions. Additionally, they noted a prevalence of loss-of-function variants in the GJB2 and ABCC2 genes, which are associated with hearing loss and chronic liver disease, respectively.
Terao aims to connect genetic differences with population health outcomes, stating, “We are cataloging loss-of-function gene variants specific to Japanese people to understand their association with particular traits and diseases.” In the future, he hopes to expand the JEWEL database to include even more genetic samples, emphasizing the need for more inclusive genomic research that benefits diverse populations.
For years, large-scale genomic studies have predominantly focused on individuals of European descent. Terao asserts the importance of broadening this scope to include Asian populations, ensuring that the benefits of genomic research are accessible to all.
In conclusion, this study not only reshapes our understanding of Japanese ancestry but also paves the way for advancements in personalized medicine, demonstrating the critical intersection between genetics, health, and historical migration patterns.
