For the first time, an international study led by the Institute of Evolutionary Biology (IBE), a joint center of the Spanish National Research Council (CSIC) and Pompeu Fabra University (UPF), together with the University of São Paulo, has deciphered the genome of Indigenous American populations. With 199 genomes from individuals from North America to Patagonia, 128 of which have never been published, the research has compiled the largest genomic database to date. Its results shed light on the history of these peoples and provide new insights into human health and evolution.

Research into human genomic diversity has a number of applications in biomedicine, evolution, and history. However, many populations have historically been underrepresented on the human genomic map. This is the case of Native American populations, whose history of adaptation and genetic diversity remains largely unknown.

The largest genetic database of Indigenous American populations

The research, part of the Indigenous American Genomic Diversity Project (IAGDP), has sequenced 128 high-coverage whole genomes from eight Latin American countries—Argentina, Bolivia, Brazil, Colombia, Ecuador, Mexico, Paraguay, and Peru—representing 45 populations and 28 linguistic families.

High-quality genomes from pre-existing databases were added to this data, taking the total to 199 contemporary indigenous individuals from 53 populations and 31 linguistic families. Ancient DNA data was also incorporated to enable a deeper look into certain aspects of their history and evolution.

“Until now, only two indigenous Amazonian populations had been genetically characterized, and due to the particular nature of their environment and their isolation, they were not very representative”, explains Marcos Araújo Castro e Silva, a postdoctoral researcher at the IBE and first author of the paper.

This study brings together the largest genomic dataset of these populations, with an emphasis on their geographic and linguistic diversity.

Genetic diversity waiting to be explored: over a million new variants

The research identified over a million genetic variants not previously observed in other populations, revealing a unique genetic diversity.

The Americas span a wide variety of landscapes and ecological pressures, from the Amazon rainforests to the high altitudes of the Andes. This has favored the selection of different genetic variants that have helped adapt human populations to these environments. The researchers were able to identify genetic signals of natural selection related to immune response, metabolism, growth, and fertility.

“These results demonstrate the need to better represent these populations in genomics. From drug design to disease prevention, understanding human genomic diversity benefits both indigenous communities and the global population”, says Tábita Hünemeier, principal investigator at the IBE and leader of the study. In 2023, her team described genetic resistance to Chagas disease in Amazonian populations, and she spearheaded the “DNA do Brasil” project published in 2025.

New findings in the history of Native American peoples

The movement of Asian populations into the Americas via Beringia represented the last major continental human migration. With the exception of a few populations, most located in the Arctic, all current indigenous Americans are descended from a migration that occurred approximately 15,000 years ago.

The first expansion occurred immediately after these people entered North America. However, around 9,000 years ago, a second wave of migration took place that replaced, at least in part, the first. For the first time, this study has identified a third wave of migration. It occurred approximately 1,300 years ago, with the movement of indigenous populations from Mesoamerica to South America and the Caribbean. The team has discovered its genetic footprint in current South American populations as well as in ancient individuals from the Caribbean.

 Three major dispersals shaped the genetic diversity of the indigenous peoples of South America. Credit: Marcos Araújo Castro e Silva.

The research also confirms the profound “bottleneck” effect caused by European colonization. “Current genetic diversity is only a fraction of the original, as colonization decimated indigenous populations by 90%. Even so, we can see genetic continuity spanning more than 9,000 years in some regions”, says Hünemeier.

Ancestral genetics of Native Americans revealed

The study reveals that around 2% of the genome of some indigenous American peoples shows genetic affinity with populations in Australasia, including those in Australia, New Guinea, and the Andaman Islands. This connection, present in South American individuals dating back more than ten thousand years and in very similar proportions, suggests the influence of an ancient, unsampled Asian population, known as Ypykuéra (Y-lineage), which intermixed with the ancestors of these populations.

“We observed that the frequency of this Ypykuéra ancestry is very similar across the different populations analyzed, perhaps indicating a certain adaptive advantage in some of these genomic regions”, explains David Comas, principal investigator at the IBE and professor and a researcher in the Department of Medicine and Life Sciences (MELIS) at the UPF, who collaborated on the study.

  Proportions of genetic ancestry inferred from the DNA analyzed in the study (unsupervised ADMIXTURE). The average ancestry of each population is represented on a map of the Americas. Credit: Marcos Araújo Castro e Silva.

The study also confirms that between 1% and 3% of the genome comes from archaic hominids, such as Neanderthals and Denisovans, a proportion similar to that seen in other regions, although there is a distinctive pattern. Importantly, these hominids contributed genetic variants that proved key to adaptation to the American continent, as evidenced by signs of natural selection found in the genome.

The results shed light on the history of these populations, expand our understanding of their past, and provide new insights for future applications in global health.

“The team is international, with a strong Latin American presence and local ties in the countries under study, and has collaborated directly with indigenous communities. The active and ongoing participation of various groups was essential not only for the study’s development but also to integrate genomic findings with traditional knowledge”, notes Hünemeier.

The study was funded by the European Union’s Horizon 2020 Research and Innovation Program/Marie Skłodowska-Curie, the “European Union NextGeneration” initiative, and a Juan de la Cierva grant from Spain’s State Research Agency, among others.

Referenced article:

Araújo Castro e Silva, M., Nunes, K., Ribeiro, M. R., Passareli-Araujo, H., Barbosa Lemes, R., Kimura, L., Sacuena, P., Amorim, C. E. G., Bortolini, M. C., Mill, J. G., Guerreiro, J. F., Barbieri, C., Hernández-Zaragoza, D. I., Walter, A., Chowdhury, T. N., Herrera-Macías, D., Lara-Riegos, J. C., Del Castillo-Chávez, O., Zurita, C., Tito-Álvarez, A. M., Vásquez-Domínguez, E., Moo-Mezeta, M. E., Torres-Romero, J. C., Aguilar-Campos, A., Serrano-Osuna, R., Parolín, M. L., Bravi, C. M., Ramallo, V., Baillet, G., Revollo, S., Sandoval, J. R., Fujita, R., Barquera, R., Santos, F. R., Comas, D., & Hünemeier, T. (in press). Indigenous American genomes reveal unique diversity and evolution. Nature. DOI: 10.1038/s41586-026-10406-w