Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Bobowik, Katalina S  ORCID logo  https://orcid.org/0000-0002-7030-3969
Kusuma, Pradiptajati  ORCID logo  https://orcid.org/0000-0002-9722-4048
Crenna Darusallam, Chelzie 

Abstract

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.

Description

Keywords

CpG Islands, DNA Methylation, Environment, Epigenesis, Genetic, Ethnicity, Gene Expression Profiling, Gene-Environment Interaction, Genetics, Population, Genome-Wide Association Study, Genomics, Humans, Indonesia, Islands, Pacific Islands, Pedigree, Phenotype, Polymorphism, Single Nucleotide, RNA-Seq, Transcriptome

Journal Title

PLoS Genet

Conference Name

Journal ISSN

1553-7390
1553-7404

Volume Title

16

Publisher

Public Library of Science (PLoS)