For decades, scientists believed that Japan’s population was primarily descended from two ancient groups. One is the Jomon period hunter-gatherers who lived on the archipelago for thousands of years, and the other is the East Asian immigrants who later brought rice cultivation and new technologies to Japan.
But a large-scale genetic analysis by researchers at the RIKEN Center for Integrative Medical Sciences suggests the picture is much more complex.
Using whole-genome sequencing of more than 3,200 people across Japan, the research team found evidence supporting a third ancestral group with ties to northeast Asia and possibly related to ancient Emishi. The survey results are scientific progressadds strong support to the increasingly debated “tripartite origin” theory of Japanese ancestry.
The results also revealed another surprise. That said, Japan’s population is more genetically diverse than many researchers once assumed.
“Japanese people are not as genetically homogeneous as people think,” says Shinji Terao, who led the study at RIKEN. “Our analysis reveals Japan’s sub-population structure at a detailed scale, very beautifully categorized according to geographic location within the country.”
Japan’s huge DNA map
To explore Japan’s deep genetic history, researchers analyzed DNA samples taken from seven regions, from Hokkaido in the north to Okinawa in the south. This project was one of the largest whole-genome studies ever conducted in a non-European population.
Instead of relying on older DNA microarray methods, the research team used whole-genome sequencing, which reads nearly all of the 3 billion DNA base pairs in a person’s genome. Researchers say this yields about 3,000 times more information than traditional techniques.
“Whole genome sequencing gives us the opportunity to examine more data, which helps us find more interesting things,” Terao explained.
The scientists then combined the genetic information with medical history, disease diagnoses, family history, and laboratory test results to build a large database known as the Japan Whole Genome/Exome Sequencing Library (JEWEL).
One particularly important focus was on rare genetic variations. These unusual DNA changes may preserve clues about ancient migration patterns or long-lost ancestral populations.
“We thought that rare variants could be traced back to specific ancestral populations and could be useful in revealing detailed migration patterns within Japan,” Terao said.
hidden three ancestors
The analysis revealed significant regional differences across Japan.
Jomon ancestry was strongest in Okinawa, where it was found in 28.5% of samples, but at much lower levels in western Japan at 13.4%. The researchers found that people in western Japan have strong genetic ties to the Han Chinese population, likely reflecting a wave of large-scale migration from the East Asian continent between 250 and 794 AD. These migrations also occurred at the same time that Chinese-style government systems, writing, and education spread throughout Japan.
The newly identified Ezo-related ancestors are concentrated in northeastern Japan, and are less common further west.
The findings build on earlier ancient DNA research published in 2021 that first proposed the idea that modern Japanese people had three main ancestral origins instead of two. These studies suggest that the third migration associated with the Kofun period played a major role in the formation of modern Japan.
Recent follow-up research further strengthens that idea. Researchers analyzing ancient genomes and human bones have found growing evidence that multiple waves of migration invaded Japan over the centuries, creating a much more layered population history than previously thought.
Ancient Neanderthal and Denisovan DNA still influences people today
The study also examined genetic material inherited from two ancient human groups that interbred with Neanderthals and Denisovans. wise person Tens of thousands of years ago.
Scientists are becoming increasingly interested in why some of these ancient DNA fragments persist in modern humans while others disappear. In many cases, inherited genes appear to be associated with health, adaptation, or disease risk.
For example, previous research showed that Tibetans inherited a Denisova-related version of the EPAS1 gene, which may help humans survive in high-altitude environments. Researchers had also previously identified Neanderthal-derived DNA associated with severe COVID-19 complications in some populations.
Japanese genome research has identified 44 archaic DNA regions that are still present in modern Japanese populations, many of which are unique to East Asians. One Denisovan-derived region within the NKX6-1 gene is associated with type 2 diabetes and may influence how some patients respond to semaglutide treatment.
Researchers also discovered 11 gene segments from Neanderthals that are associated with diseases such as coronary artery disease, prostate cancer, and rheumatoid arthritis.
Towards personalized medicine
In addition to tracing ancestry, researchers believe this research could ultimately improve medical care.
The research team has identified potentially harmful variants in the PTPRD gene that may be associated with high blood pressure, kidney failure, and myocardial infarction. They also discovered common loss-of-function variants in the GJB2 and ABCC2 genes that are associated with hearing loss and chronic liver disease.
“What we tried to do was find and catalog loss-of-function gene variants that are very specific to the Japanese population and understand why the Japanese population is more susceptible to certain traits and diseases,” Professor Terao said. “We want to link population differences to differences in genetics.”
This study reflects broader changes occurring in genetics research. For many years, most large genomic databases focused on people of European descent, limiting scientists’ understanding of disease risk in other populations.
Terao hopes that expanding JEWEL with more Asian genomic data will help change this situation.
“It is very important that we extend this to the people of Asia so that in the long run the results benefit us as well,” he said.
