Biology subjects

Kusuma, P.

Publications and source records attributed to Kusuma, P..

8 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↗

bioRxiv2026

Ancestral and environmental diversity shape the immune landscape in Indonesia

Island Southeast Asia (ISEA) remains consistently underrepresented in human genomic resources despite its exceptional ancestral and lifestyle diversity. The interplay between the regions complex population history and its environmental variation provide a window into how ancestry and environment jointly shape the human immune system. Here we report the generation of single-cell PBMC profiles from 199 Indonesians sampled across four communities in the islands of Bali and New Guinea. These groups capture diversity in regional genetic ancestries (East Asian-like and Papuan-like) and lifestyle contrasts (urban versus rural communities in Bali; highland versus lowland communities in New Guinea). We identify over 4,000 expression quantitative trait loci (eQTLs) across nine immune cell types, including eQTLs driven by introgression from both Neanderthals and Denisovans at genes such as IL7R, HLA-E, or STAT2. We also find evidence of local ancestry driving gene-by-environment interactions at pathogen receptors such as MARCO, although the majority of gene-by-environment interactions are not driven by differences in genetic structure between populations. Beyond direct genetic effects, we construct gene co-expression networks that consistently identify environmental signatures, as well as T-cell receptor repertoires that distinguish specific communities, with excess representation of interferon-stimulated genes in rural, but not urban samples. This work establishes a framework for population-aware functional genomics in understudied regions and highlights how ancestral and environmental diversity jointly shape human immunity in this globally important yet underrepresented region.

genomics↗

bioRxiv2025

From sporulation to village differentiation: the shaping of the social microbiome over rural-to-urban lifestyle transition in Indonesia

Despite established roles in human health and profound global diversity, existing gut microbiome datasets are biased toward Western urban cohorts, with especial under-representation of Southeast Asia. Here, we present a novel gut microbiome dataset from 116 Indonesians representing a cline from transitional hunter-gatherers to rural agricultural to urban lifestyles. We identify 1,304 species and 3,258 subspecies by assembling 11,070 metagenome-assembled genomes, revealing substantial species (15%) and subspecies level (50%) novelty. Novel taxa are rare, often village-specific, and depleted for sporulation genes, revealing a direct link between bacterial physiology, transmission, prevalence and discovery. We identify a rural-to-urban cline across multiple levels of biological organisation, from species abundance to microbiome composition and diversity. Furthermore, between-community, but not within-community, variation in diet is strongly predictive of microbiome composition, offering compelling evidence that microbiome divergence is driven by community-level differences. Our work highlights the interplay of host lifestyle, population structure and bacterial physiology in shaping microbiome diversity and biogeography, at the key scale of human communities.

microbiology↗

bioRxiv2024

Profiling genetically driven alternative splicing across the Indonesian Archipelago

One of the regulatory mechanisms influencing the functional capacity of genes is alternative splicing (AS). Previous studies exploring the splicing landscape of human tissues have shown that AS has contributed to human biology, especially in disease progression and the immune response. Nonetheless, this phenomenon remains poorly characterised across human populations, and it is unclear how genetic and environmental variation contribute to alternative splicing. Here, we examine a set of 115 Indonesian samples from three traditional island populations spanning the genetic ancestry cline that characterizes Island Southeast Asia. We conduct a global AS analysis between islands to ascertain the degree of functionally significant AS events and their consequences. Using a hierarchical event-based statistical model, we detected over 1,000 significant differential AS events across all comparisons. Additionally, we identify over 6,000 genetic variants associated with changes in splicing (splicing quantitative trait loci; sQTLs), some of which are driven by Papuan-like genetic ancestry, and only show partial overlap with other publicly available sQTL datasets derived from other populations. Computational predictions of RNA binding activity revealed that a fraction of these sQTLs directly modulate the binding propensity of proteins involved in the splicing regulation of immune genes. Overall, these results contribute towards elucidating the role of genetic variation in shaping gene regulation in one of the most diverse regions in the world.

genomics↗

bioRxiv2022

The whole blood microbiome of Indonesians reveals that environmental differences shape immune gene expression signatures

Pathogens found within local environments are a major cause of morbidity and mortality. This is particularly true in Indonesia, where infectious diseases such as malaria or dengue are a significant part of the disease burden. Unequal investment in medical funding throughout Indonesia, particularly in rural areas, has resulted in under-reporting of cases, making surveillance challenging. Here, we use transcriptome data from 117 healthy individuals living on the islands of Mentawai, Sumba, and the Indonesian side of New Guinea Island to explore which pathogens are present within whole blood. We detect a range of taxa within RNA-sequencing data generated from whole blood and find that two pathogens--Flaviviridae and Plasmodium--are the most predominantly abundant, both of which are most pronounced in the easternmost island within our Indonesian dataset. We also compare the Indonesian data to two other cohorts from Mali and UK and find a distinct microbiome profile for each group. This study provides a framework for RNA-seq as a possible retrospective surveillance tool and an insight to what makes up the transient human blood microbiome.

genomics↗

bioRxiv2020

Genetic architecture of gene regulation in Indonesian populations identifies QTLs associated with local ancestry and archaic introgression

Lack of diversity in human genomics limits our understanding of the genetic underpinnings of complex traits, hinders precision medicine, and contributes to health disparities. To map genetic effects on gene regulation in the underrepresented Indonesian population, we have integrated genotype, gene expression, and CpG methylation data from 115 participants across three island populations that capture the major sources of genomic diversity on the region. In a comparison with a European dataset, we identify 166 uniquely Indonesia-specific eQTLs, highlighting the benefits of performing association studies on non-European populations. By combining local ancestry and archaic introgression inference eQTLs and methylQTLs, we identify regulatory loci driven by modern Papuan ancestry as well as introgressed Denisovan and Neanderthal variation. GWAS colocalization connects QTLs detected here to hematological traits. Our findings illustrate how local ancestry and archaic introgression drive variation in gene regulation across genetically distinct and in admixed populations.

genomics↗

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↗

bioRxiv2019

Manipulation of Seedling Traits with Pulsed Light in Closed Controlled Environments

There is substantial interest in growing crops in closed controlled environments, yet the energy requirements are high. Energy is required to produce light, but also to remove the heat generated when producing light. The goal of the current work examines a possible approach to decrease the energy requirement. The effect of pulsed light treatments was examined by monitoring seedling traits during early photomorphogenic development. Daily light integral remained unchanged between treatments, but the frequency of the pulses was varied. Developmental traits (such as inhibition of hypocotyl elongation rate) were most conspicuous during a normal photoperiod, as in twelve hours light, twelve hours darkness. Consistent with historical reports, when treatments were delivered in shorter durations (e.g. 1 hour on/off) photomorphogenic development was hindered, with the same daily light integral. However, at even shorter light intervals (e.g. seconds) seedlings developed as if they were provided full 12 h treatments. Extension of the dark period following a 5 s pulse was tested to determine the effect on seedling traits. The results showed that the dark period could be extended to at least 10 s without affecting seedling development, and extension to 20 s only had slight effects on seedling traits. The mechanism of the phenomenon was examined in Arabidopsis photosensory mutants, with substantial contributions from the phyA and cry1 pathways. The results suggest that pulsed light with extended dark periods can decrease energy input by at least 30% to >50% without affecting visible seedling traits. These pilot experiments in seedlings demonstrate that implementation of short-interval, pulsed-light strategies may lower energy requirements for growing crops in artificially illuminated environments.

plant biology↗