Rapid convergence toward an agriculturalist regulatory landscape following lifestyle transition in Bornean hunter-gatherers

Abstract

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.