Biology subjects

Jacobs, G. S.

Publications and source records attributed to Jacobs, G. S..

4 recordsLinked to original sources

bioRxiv2026

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

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.

evolutionary biology↗

bioRxiv2020

Introgression, hominin dispersal and megafaunal survival in Late Pleistocene Island Southeast Asia

The hominin fossil record of Island Southeast Asia (ISEA) indicates that at least two endemic super-archaic species - Homo luzonensis and H. floresiensis - were present around the time anatomically modern humans (AMH) arrived in the region >50,000 years ago. Contemporary human populations carry signals consistent with interbreeding events with Denisovans in ISEA - a species that is thought to be more closely related to AMH than the super-archaic endemic ISEA hominins. To query this disparity between fossil and genetic evidence, we performed a comprehensive search for super-archaic introgression in >400 modern human genomes. Our results corroborate widespread Denisovan ancestry in ISEA populations but fail to detect any super-archaic admixture signals. By highlighting local megafaunal survival east of the Wallace Line as a potential signature of deep, pre-H. sapiens hominin-faunal interaction, we propose that this understudied region may hold the key to unlocking significant chapters in Denisovan prehistory.

evolutionary biology↗

bioRxiv2019

Characterisation of a second gain of function EDAR variant, encoding EDAR380R, in East Asia

EDAR is a TNF receptor family member with roles in the development and growth of hair, teeth and glands. A derived allele of EDAR, single nucleotide variant rs3827760, encodes EDAR370A, a receptor with more potent signalling effects than the ancestral EDAR370V. This allele of rs3827760 is at very high frequency in modern East Asian and Native American populations as a result of ancient positive selection and has been associated with straighter, thicker hair fibres, alteration of tooth and ear shape, reduced chin protrusion and increased fingertip sweat gland density. Here we report the characterisation of another SNV in EDAR, rs146567337, encoding EDAR380R. The derived allele of this SNV is at its highest global frequency, of up to 5%, in populations of southern China, Vietnam, the Philippines, Malaysia and Indonesia. Using haplotype analyses, we find that the rs3827760 and rs146567337 SNVs arose on distinct haplotypes and that rs146567337 does not show the same signs of positive selection as rs3827760. From functional studies in cultured cells, we find that EDAR380R displays increased EDAR signalling output, at a similar level to that of EDAR370A. The existence of a second SNV with partly overlapping geographic distribution, the same in vitro functional effect and similar evolutionary age as the derived allele of rs3827760, but of independent origin and not exhibiting the same signs of strong selection, suggests a northern focus of positive selection on EDAR function in East Asia.

genetics↗

bioRxiv2019

Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago

Indonesia is the worlds fourth most populous country, host to striking levels of human diversity, regional patterns of admixture, and varying degrees of introgression from both Neanderthals and Denisovans. However, it has been largely excluded from the human genomics sequencing boom of the last decade. To serve as a benchmark dataset of molecular phenotypes across the region, we generated genome-wide CpG methylation and gene expression measurements in over 100 individuals from three locations that capture the major genomic and geographical axes of diversity across the Indonesian archipelago. Investigating between- and within-island differences, we find up to 10% of tested genes are differentially expressed between the islands of Mentawai (Sumatra) and New Guinea. Variation in gene expression is closely associated with DNA methylation, with expression levels of 9.7% of genes strongly correlating with nearby CpG methylation, and many of these genes being differentially expressed between islands. Genes identified in our differential expression and methylation analyses are enriched in pathways involved in immunity, highlighting Indonesia tropical role as a source of infectious disease diversity and the strong selective pressures these diseases have exerted on humans. Finally, we identify robust within-island variation in DNA methylation and gene expression, likely driven by very local environmental differences across sampling sites. Together, these results strongly suggest complex relationships between DNA methylation, transcription, archaic hominin introgression and immunity, all jointly shaped by the environment. This has implications for the application of genomic medicine, both in critically understudied Indonesia and globally, and will allow a better understanding of the interacting roles of genomic and environmental factors shaping molecular and complex phenotypes.

genomics↗