The transition from hunter-gatherer to agricultural lifestyles is one of the landmarks in the history of human societies, but its phenotypic and immediate molecular consequences remain poorly understood. The Punan of Borneo clarify this question: two closely related groups — the Punan Batu, still practising mobile foraging, and the Punan Tubu, resettled and farming within the last three generations — share deep common ancestry and no detectable post-split gene flow from agricultural neighbours, allowing the molecular consequences of lifestyle change to be separated from underlying genetic architecture. We applied a multi-omics approach across these two groups and a neighbouring agriculturalist community, the Lundayeh, profiling whole-genome sequences, blood transcriptomes, and DNA methylation arrays. Despite their shared ancestry, the resettled Punan exhibit transcriptomic and methylation profiles more similar to the agriculturalists than to their still-foraging Punan relatives, with 87% fewer differentially expressed genes and substantially fewer differentially methylated sites in the Punan Tubu versus Lundayeh comparison, and show a 77% shift towards an agricultural state. Genes associated with fat metabolism and immune function are the main components of this molecular convergence. These findings demonstrate that lifestyle transition can reshape the human transcriptome and DNA methylation on timescales far shorter than genomic evolution, with implications for understanding the biological consequences of rapid subsistence change in Indigenous communities worldwide.

Population and medical genetics can provide valuable information about human history and health. However, research involving Indigenous and vulnerable communities often raises ethical issues and runs the risk of being extractive and harmful. Here we argue that meaningful community engagement in genetic research involving communities is both a moral and scientific obligation and present practical guidance based on empirical work. Drawing on a long-term project with the Bornean hunter-gatherer community, the Punan Batu, we describe an engagement workflow that combines community consultation, co-design, dynamic consent, respectful sample and data collections, return of results, and impactful benefit sharing. These activities supported scientifically useful outcomes and produced targeted tangible community benefits, such as health services, recognition of the community’s traditional and legal status, environmental awards, and ongoing support for their land rights. We place the Bornean hunter-gatherer case in comparative perspective with cases of past harm, research fatigue, and contemporary partnership models in genomic research. We show how proper engagement reduces the risk of misinterpretation, data misuse, and public criticism, and how it can be resourced, monitored, and rewarded. Finally, we provide recommendations for stakeholders, i.e., funders, IRBs, institutions, and researchers, to integrate engagement into grant review, ethics assessment, and project design. Respectful engagement takes time and may slow conventional short-term academic progress, but it strengthens scientific validity, equity, and long-term impact – a tradeoff that all stakeholders should acknowledge and support.

Borneo was a crossroad of ancient dispersals, with some of the earliest Southeast Asian human remains and rock art. The island is home to traditionally hunter-gatherer Punan communities, whose origins, whether of subsistence reversion or long-term foraging, are unclear. The connection between its past and present-day agriculturalist inhabitants, who currently speak Austronesian languages and have composite and complex genetic ancestry, is equally opaque. Here, we analyze the genetic ancestry of the northeastern Bornean Punan Batu (who still practice some mobile hunting and gathering), Tubu, and Aput. We find deep ancestry connections, with a shared Asian signal outgrouping modern and ancient Austronesian-ancestry proxies, suggesting a time depth of more than 7,500 years. They also largely lack the mainland Southeast Asian signals of agricultural Borneans, who are themselves genetically heterogeneous. Our results support long-term inhabitation of Borneo by some Punan ancestors and reveal unexpected complexity in the origins and dispersal of Austronesian-expansion-related ancestry.

Abstract Theories of early cooperation in human society often draw from a small sample of ethnographic studies of surviving populations of hunter–gatherers, most of which are now sedentary. Borneo hunter–gatherers (Punan, Penan) have seldom figured in comparative research because of a decades-old controversy about whether they are the descendants of farmers who adopted a hunting and gathering way of life. In 2018 we began an ethnographic study of a group of still-nomadic hunter–gatherers who call themselves Punan Batu (Cave Punan). Our genetic analysis clearly indicates that they are very unlikely to be the descendants of neighbouring agriculturalists. They also preserve a song language that is unrelated to other languages of Borneo. Dispersed travelling groups of Punan Batu with fluid membership use message sticks to stay in contact, co-operate and share resources as they journey between rock shelters and forest camps. Message sticks were once widespread among nomadic Punan in Borneo, but have largely disappeared in sedentary Punan villages. Thus the small community of Punan Batu offers a rare glimpse of a hunting and gathering way of life that was once widespread in the forests of Borneo, where prosocial behaviour extended beyond the face-to-face community, facilitating successful collective adaptation to the diverse resources of Borneo’s forests.

Genome sequences are known for two archaic hominins-Neanderthals and Denisovans-which interbred with anatomically modern humans as they dispersed out of Africa. We identified high-confidence archaic haplotypes in 161 new genomes spanning 14 island groups in Island Southeast Asia and New Guinea and found large stretches of DNA that are inconsistent with a single introgressing Denisovan origin. Instead, modern Papuans carry hundreds of gene variants from two deeply divergent Denisovan lineages that separated over 350 thousand years ago. Spatial and temporal structure among these lineages suggest that introgression from one of these Denisovan groups predominantly took place east of the Wallace line and continued until near the end of the Pleistocene. A third Denisovan lineage occurs in modern East Asians. This regional mosaic suggests considerable complexity in archaic contact, with modern humans interbreeding with multiple Denisovan groups that were geographically isolated from each other over deep evolutionary time.