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

Autor: Natri HM; Center for Evolution and Medicine, School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.; The Translational Genomics Research Institute, Phoenix, Arizona, United States of America., Bobowik KS; Melbourne Integrative Genomics, University of Melbourne, Parkville, Australia.; School of BioSciences, University of Melbourne, Parkville, Australia.; Centre for Stem Cell Systems, University of Melbourne, Parkville, Australia., Kusuma P; Genome Diversity and Diseases Laboratory, Eijkman Institute for Molecular Biology, Jakarta, Indonesia.; Complexity Institute, Nanyang Technological University, Singapore, Singapore., Crenna Darusallam C; Genome Diversity and Diseases Laboratory, Eijkman Institute for Molecular Biology, Jakarta, Indonesia., Jacobs GS; Complexity Institute, Nanyang Technological University, Singapore, Singapore., Hudjashov G; Statistics and Bioinformatics Group, School of Fundamental Sciences, Massey University, Palmerston North, New Zealand., Lansing JS; Santa Fe Institute, Santa Fe, New Mexico, United States of America.; Vienna Complexity Science Hub, Vienna, Austria.; Stockholm Resilience Center, Kräftriket, Stockholm, Sweden., Sudoyo H; Genome Diversity and Diseases Laboratory, Eijkman Institute for Molecular Biology, Jakarta, Indonesia.; Department of Medical Biology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.; Sydney Medical School, University of Sydney, Sydney, NSW, Australia., Banovich NE; The Translational Genomics Research Institute, Phoenix, Arizona, United States of America., Cox MP; Statistics and Bioinformatics Group, School of Fundamental Sciences, Massey University, Palmerston North, New Zealand., Gallego Romero I; Melbourne Integrative Genomics, University of Melbourne, Parkville, Australia.; School of BioSciences, University of Melbourne, Parkville, Australia.; Centre for Stem Cell Systems, University of Melbourne, Parkville, Australia.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2020 May 26; Vol. 16 (5), pp. e1008749. Date of Electronic Publication: 2020 May 26 (Print Publication: 2020).
DOI: 10.1371/journal.pgen.1008749
Abstrakt: Indonesia is the world's 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 10.55% of tested genes are differentially expressed between the islands of Sumba and New Guinea. Variation in gene expression is closely associated with DNA methylation, with expression levels of 9.80% of genes correlating with nearby promoter 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's 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 fine-scale 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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