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

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 las...

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Published in:	PLoS genetics Vol. 16; no. 5; p. e1008749
Main Authors:	Natri, Heini M, Bobowik, Katalina S, Kusuma, Pradiptajati, Crenna Darusallam, Chelzie, Jacobs, Guy S, Hudjashov, Georgi, Lansing, J Stephen, Sudoyo, Herawati, Banovich, Nicholas E, Cox, Murray P, Gallego Romero, Irene
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 26-05-2020 Public Library of Science (PLoS)
Subjects:	archipelago Archipelagoes Biology and life sciences Bisulfite controlled study CpG island CpG Islands Datasets Deoxyribonucleic acid DNA DNA methylation DNA sequencing Earth Sciences environment Environmental aspects Environmental conditions environmental factor epidemiology Epigenesis ethnic group Ethnic Groups Gene expression gene expression profiling gene identification Gene-Environment Interaction Genetic Genetic aspects genetic epigenesis genetic variation genetics Genome-wide association studies genome-wide association study Genomes Genomics genotype environment interaction geographic and geological phenomena geographic distribution heredity human human cell Humans Immune system immunity Indonesia Indonesian infection introgression island (geological) Islands male Methylation Nucleotide sequence Pacific islands Papua New Guinea pedigree People and Places phenotype Phenotypes physiology Polymorphism Population population genetics procedures promoter region Research and analysis methods Ribonucleic acid RNA RNA-Seq sampling Single Nucleotide single nucleotide polymorphism transcriptome Indonesia Mentawai Southeast Asia Sumba Europe
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Summary:	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.
Bibliography:	new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors equally led this work. The authors have declared that no competing interests exist.
ISSN:	1553-7404 1553-7390 1553-7404
DOI:	10.1371/journal.pgen.1008749