Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago
Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago
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全基因组DNA甲基化和基因表达模式反映了印度尼西亚群岛的遗传祖先和环境差异
DOI：
10.1371/journal.pgen.1008749
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发表时间：
2020-05-01
期刊：
影响因子：
4.5
通讯作者：
Romero, Irene Gallego
中科院分区：
文献类型：
--
作者：
Natri, Heini M.;Bobowik, Katalina S.;Romero, Irene Gallego
印度尼西亚是世界上第四大人口大国，拥有惊人的人类多样性，混合的区域模式，以及尼安德特人和丹尼索瓦人不同程度的渗入。然而，它在很大程度上被排除在过去十年的人类基因组测序热潮之外。为了作为该地区分子表型的基准数据集，我们在来自三个地点的100多个个体中生成了全基因组CpG甲基化和基因表达测量，这些地点捕获了印度尼西亚群岛的主要基因组和地理多样性轴。调查之间和岛屿内的差异，我们发现高达10.55%的测试基因之间的松巴岛和新几内亚的差异表达。基因表达的变化与DNA甲基化密切相关，9.80%的基因表达水平与附近的启动子CpG甲基化相关，并且这些基因中的许多基因在岛之间差异表达。在我们的差异表达和甲基化分析中鉴定的基因在免疫相关的途径中富集，突出了印度尼西亚作为传染病多样性来源的热带作用以及这些疾病对人类施加的强大选择性压力。最后，我们确定了DNA甲基化和基因表达的鲁棒岛内变异，可能是由采样点之间的精细尺度环境差异驱动的。总之，这些结果强烈表明DNA甲基化，转录，古人类基因渗入和免疫力之间的复杂关系，所有这些都是由环境共同塑造的。这对基因组医学的应用有影响，无论是在严重不足的印度尼西亚和全球范围内，并允许更好地了解基因组和环境因素塑造分子和复杂的phenotypes.Author summaryUnderstanding的相互作用基因表达如何在不同的个人和环境是分子医学的成功的基础。然而，绝大多数基因表达的研究，特别是在健康个体中，主要涉及欧洲血统的人群。目前还不清楚这些发现是否可以推广到其他人。我们研究了印度尼西亚这个世界第四人口大国的116名个体的基因表达和DNA甲基化。我们的三个种群--苏门答腊岛西海岸的明打威人、印度尼西亚中部的松巴人，以及生活在新几内亚西巴布亚省的一群狩猎采集者科罗威人--跨越了该地区遗传和地理多样性的主轴。高达10%的基因在岛之间的表达和甲基化模式上存在差异，其中许多基因与免疫功能有关。每个地点内村庄之间的差异可能归因于小规模的环境差异。这些发现强调了在研究分子模式和过程如何在人群中共享时，需要考虑广泛的遗传和环境背景。
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.Author summaryUnderstanding how gene expression varies across individuals and environments is fundamental for the success of molecular medicine. However, the vast majority of studies of gene expression, particularly in healthy individuals, have primarily involved populations of European descent. It is unclear whether these findings are generalizable to the rest of humanity. We examined gene expression and DNA methylation in 116 individuals across Indonesia, the world's fourth most populous country. Our three populations-Mentawai off the western coast of Sumatra, Sumba in central Indonesia, and a group of hunter-gatherers, the Korowai, living in the province of West Papua in New Guinea-span the main axes of genetic and geographic diversity in the region. Up to 10% of genes show differences in expression and methylation patterns between islands, with many involved in immune function. Variation between villages within each location can likely be attributed to small-scale environmental differences. These findings emphasise the need to consider a broad range of genetic and environmental backgrounds when examining how molecular patterns and processes are shared across human populations.