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


Autoři: Heini M. Natri aff001;  Katalina S. Bobowik aff003;  Pradiptajati Kusuma aff006;  Chelzie Crenna Darusallam aff006;  Guy S. Jacobs aff007;  Georgi Hudjashov aff008;  J. Stephen Lansing aff009;  Herawati Sudoyo aff006;  Nicholas E. Banovich aff002;  Murray P. Cox aff008;  Irene Gallego Romero aff003
Působiště autorů: Center for Evolution and Medicine, School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America aff001;  The Translational Genomics Research Institute, Phoenix, Arizona, United States of America aff002;  Melbourne Integrative Genomics, University of Melbourne, Parkville, Australia aff003;  School of BioSciences, University of Melbourne, Parkville, Australia aff004;  Centre for Stem Cell Systems, University of Melbourne, Parkville, Australia aff005;  Genome Diversity and Diseases Laboratory, Eijkman Institute for Molecular Biology, Jakarta, Indonesia aff006;  Complexity Institute, Nanyang Technological University, Singapore, Singapore aff007;  Statistics and Bioinformatics Group, School of Fundamental Sciences, Massey University, Palmerston North, New Zealand aff008;  Santa Fe Institute, Santa Fe, New Mexico, United States of America aff009;  Vienna Complexity Science Hub, Vienna, Austria aff010;  Stockholm Resilience Center, Kräftriket, Stockholm, Sweden aff011;  Department of Medical Biology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia aff012;  Sydney Medical School, University of Sydney, Sydney, NSW, Australia aff013
Vyšlo v časopise: Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008749
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008749

Souhrn

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.

Klíčová slova:

DNA methylation – Gene expression – Genomic medicine – Indonesia – Introgression – Islands – Population genetics – RNA sequencing


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2020 Číslo 5

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