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 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.

Ämnesord

NATURVETENSKAP  -- Geovetenskap och miljövetenskap (hsv//swe)

NATURAL SCIENCES  -- Earth and Related Environmental Sciences (hsv//eng)

Nyckelord

archipelago

Article

controlled study

CpG island

DNA methylation

environmental factor

gene expression

gene identification

genetic variation

genome-wide association study

geographic and geological phenomena

geographic distribution

heredity

human

human cell

immunity

Indonesia

Indonesian

infection

introgression

male

Papua New Guinea

promoter region

sampling

environment

epidemiology

ethnic group

gene expression profiling

genetic epigenesis

genetics

genomics

genotype environment interaction

island (geological)

Pacific islands

pedigree

phenotype

physiology

population genetics

procedures

single nucleotide polymorphism

transcriptome

CpG Islands

Epigenesis

Genetic

Ethnic Groups

Gene-Environment Interaction

Genetics

Population

Humans

Islands

Polymorphism

Single Nucleotide

RNA-Seq

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)