Europe was deep in the Middle Ages when halfway around the world, on the remote, windswept shores of tiny Easter Island, a group of skilled seafarers prepared for a long voyage. They stocked their double-hulled catamarans with taro, sweet potato and bananas — food for many weeks at sea, but also, they hoped, to plant on a distant land they would make their new home.
There is no written record of their journey, but Stanford Medicine researchers and collaborators analyzing the genomes of modern-day Polynesians have discovered indelible genetic evidence that ancient sailors from this region did settle a faraway land. To the researcher's surprise, their new home was Hawaii, some 7,000 kilometers away, among the most distant Polynesian islands from Easter Island.
The findings are reported in a study published Oct. 8 in Science.
"What we uncover in this paper is where the native people of Hawaii had come from," said Alexander Ioannidis , PhD, assistant professor of genetics and of biomedical data science, and co-senior author of the study. "Hawaii is the only Polynesian island in the Northern Hemisphere, so it's a long way from everything."
The other co-senior author is Keolu Fox, PhD, an associate professor of anthropology at the University of California, San Diego, and a Native Hawaiian.
Polynesia consists of more than 1,000 islands spread over an area of the Pacific Ocean roughly equivalent to the areas of North and South America combined. Tropical, lush Hawaii is about as far away from temperate Easter Island in the far south Pacific as San Francisco is from Lima, Peru.
But the new findings do more than help reconstruct the settlement of Polynesia and add to evidence of an ancient ultravoyaging culture — they also identify genetic bottlenecks that have profound implications for precision medicine and disease risks among modern Polynesians.
Founder effects
These genetic bottlenecks are known as founder effects when they result from a small portion of a population separating and founding a new population. This narrowing of the gene pool can amplify the frequency of otherwise rare genetic variants, sometimes linked to disease. Founder effects have been well studied in groups of European descent like the Amish, the Ashkenazi Jews and the Finns, resulting in standard screenings for certain genetic conditions in these groups.
The new study reveals that an even stronger founder effect has been overlooked among Native Hawaiians.
"What we discovered is in the Eastern Polynesians, such as Native Hawaiians, the founder effects are more than an order of magnitude, so more than 10 times, larger than what we have in the populations of European descent we've studied so well," Ioannidis said.
That's because Native Hawaiians sit at the end of a long sequence of genetic bottlenecks as their ancestors sent off small groups, perhaps only a few hundred individuals at a time, to settle new islands over the course of a few centuries.
An earlier genetic study by the researchers had traced the settlement of Polynesia from Samoa to Fiji and Tonga, then gradually eastward to the Cook Islands, the Society Islands (including Tahiti), Mangareva and ultimately Easter Island around the year 1210. But the longest journey was still to come.
"We thought Easter Island was the end when we were first doing that study, but now it looks like it was part of this path to Hawaii, which is really incredible," Ioannidis said. "By the time you've gotten all the way to Hawaii, you're at the end of a series of founder effects, so it's really intense."
Encoded genealogy
The researchers made their latest discovery by analyzing the genomes of over 1,000 individuals throughout Polynesia.
"People on the islands today have encoded in their genomes essentially the genealogy of all of their ancestors," Ioannidis said.
They focused on genome segments of Polynesian ancestry, removing more recent additions of European and Asian ancestry, for example. They compared the length of chromosomal segments, known as identity-by-descent segments, shared among people from different islands. The longer the shared segments between two people, the more recently they shared a common ancestor.
They found that Hawaiians share the most Polynesian ancestry with people on Easter Island, followed by people on Mangareva, an island nearly 3,000 kilometers east of Easter Island. Though no one had connected these distant dots previously, it makes sense that an ultravoyaging culture capable of reaching Easter Island from Mangareva would be the one to then settle Hawaii, Ioannidis said. (An earlier study by the researchers found that members of the same ultravoyaging population also reached South America and came in contact with Native Americans.)
The team also conducted a more detailed genomic analysis of people from Tahiti, the island for which they had the most genomes. By comparing identity-by-descent segments within the population, they could estimate the size and date of the founding generation — a group of approximately 800 people who arrived on the island about 34 generations ago, around the year 1070. (The population estimate is of a single generation of reproductive age and doesn't include children and elders they may have brought along.)
"Archaeologists and others have long wondered how many people founded these islands. That's not something that you can determine definitively from archaeology, but we can determine it from genetics," Ioannidis said.
The genomic analysis also reconstructed the rapid population growth on Tahiti after the initial settlement and a significant population crash in the 1700s following European colonial contact.
The researchers are working on similar reconstructions for Easter Island and Hawaii, which will require more genomes.
Clinical urgency
But more pressing is the need for large-scale genomic studies to identify clinically relevant variants that may be unusually prevalent among Polynesians.
The researchers analyzed three variants that recently have been linked to autosomal recessive conditions (requiring two copies of the gene) among Eastern Polynesians: ADAMTSL4, which can cause dislocated lens in the eyes; PDE6B, which can cause progressive vision loss; and FAN1, which can lead to kidney failure.
These variants are exceedingly rare among the global population and hardly present in international genome databases, but they are carried by 2% to 3% of the Eastern Polynesians studied. That level meets standard thresholds for genetic screening recommendations.
"We should be doing more sequencing and trying to characterize more of these conditions among Native Hawaiians," said Ioannidis, noting that the Native Hawaiian population is nearly twice the size of the Amish population, yet still lacks genetic testing guidelines. "We don't have recommendations for genetic testing, and there's no reimbursement from insurance because these are conditions we don't even know about."
"This is a population that should be getting research resources and attention from geneticists even more urgently."
Researchers from the University of California, Santa Cruz; Variant Bio; Direction de la Santé de Polynésie Française in Tahiti; Hôpital Saint-Philibert in France; the University of Chile; the National Polytechnic Institute in Mexico; and the University of Alabama at Birmingham contributed to the study.
The study received funding from the National Institutes of Health (grants T32HG012344, U01HG007417 and U01HG007419).
