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...
Saved in:
Main Authors: | , , , , , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2021
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/146860 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-146860 |
---|---|
record_format |
dspace |
institution |
Nanyang Technological University |
building |
NTU Library |
continent |
Asia |
country |
Singapore Singapore |
content_provider |
NTU Library |
collection |
DR-NTU |
language |
English |
topic |
Science::Physics DNA Methylation Gene Expression |
spellingShingle |
Science::Physics DNA Methylation Gene Expression Natri, Heini M. Bobowik, Katalina S. Kusuma, Pradiptajati Darusallam, Chelzie Crenna Jacobs, Guy S. Hudjashov, Georgi Lansing, J. Stephen Sudoyo, Herawati Banovich, Nicholas E. Cox, Murray P. Gallego Romero, Irene Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago |
description |
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. |
author2 |
School of Physical and Mathematical Sciences |
author_facet |
School of Physical and Mathematical Sciences Natri, Heini M. Bobowik, Katalina S. Kusuma, Pradiptajati Darusallam, Chelzie Crenna Jacobs, Guy S. Hudjashov, Georgi Lansing, J. Stephen Sudoyo, Herawati Banovich, Nicholas E. Cox, Murray P. Gallego Romero, Irene |
format |
Article |
author |
Natri, Heini M. Bobowik, Katalina S. Kusuma, Pradiptajati Darusallam, Chelzie Crenna Jacobs, Guy S. Hudjashov, Georgi Lansing, J. Stephen Sudoyo, Herawati Banovich, Nicholas E. Cox, Murray P. Gallego Romero, Irene |
author_sort |
Natri, Heini M. |
title |
Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago |
title_short |
Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago |
title_full |
Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago |
title_fullStr |
Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago |
title_full_unstemmed |
Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago |
title_sort |
genome-wide dna methylation and gene expression patterns reflect genetic ancestry and environmental differences across the indonesian archipelago |
publishDate |
2021 |
url |
https://hdl.handle.net/10356/146860 |
_version_ |
1759857375323357184 |
spelling |
sg-ntu-dr.10356-1468602023-02-28T19:28:41Z Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago Natri, Heini M. Bobowik, Katalina S. Kusuma, Pradiptajati Darusallam, Chelzie Crenna Jacobs, Guy S. Hudjashov, Georgi Lansing, J. Stephen Sudoyo, Herawati Banovich, Nicholas E. Cox, Murray P. Gallego Romero, Irene School of Physical and Mathematical Sciences Complexity Institute Science::Physics DNA Methylation Gene Expression 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. Ministry of Education (MOE) Published version This work was supported by Royal Society of New Zealand Marsden Grant 17-MAU-040 to MPC and IGR (https://www.royalsociety. org.nz/); National Science Foundation Grant SES 0725470 to JSL (http://www.nsf.gov); Singapore Ministry of Education Tier II Grant MOE2015-T2-1-127 to JSL (https://www.moe.gov.sg/); NTU Presidential Postdoctoral Fellowship to GSJ (http:// www.ntu.edu.sg); NTU Complexity Institute Individual Fellowship to PK (http://www.ntu.edu. sg), ASU Center for Evolution and Medicine postdoctoral fellowship to HMN (https://evmed. asu.edu/), a Prevent Cancer Foundation award to HMN (https://preventcancer.org/research/grants-fellowships/), a University of Melbourne Graduate Research Scholarship to KSB (http://www.unimelb. edu.au) and a University of Melbourne Miegunyah Distinguished Visiting Professor fellowship to MPC (http://www.unimelb.edu.au). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We especially thank all of our study participants and the Eijkman Institute field survey team, without whom this work would not have been possible. We thank Nicolas Brucato (University de Toulouse Midi-Pyrénées), Christine Wells (University of Melbourne), Davide Vespasiani (University of Melbourne) and Isabella Apriyana (Australian National University) for valuable discussion. 2021-03-12T07:39:22Z 2021-03-12T07:39:22Z 2020 Journal Article Natri, H. M., Bobowik, K. S., Kusuma, P., Darusallam, C. C., Jacobs, G. S., Hudjashov, G., Lansing, J. S., Sudoyo, H., Banovich, N. E., Cox, M. P. & Gallego Romero, I. (2020). Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago. PLoS Genetics, 16(5). https://dx.doi.org/10.1371/journal.pgen.1008749 1553-7390 https://hdl.handle.net/10356/146860 10.1371/journal.pgen.1008749 32453742 2-s2.0-85086051824 5 16 en MOE2015-T2-1-127 PLoS Genetics © 2020 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. application/pdf |