Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution

Jia Zeng, Genevieve Konopka, Brendan G. Hunt, Todd M. Preuss, Dan Geschwind, Soojin V. Yi

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

DNA methylation is a pervasive epigenetic DNA modification that strongly affects chromatin regulation and gene expression. To date, it remains largely unknown how patterns of DNA methylation differ between closely related species and whether such differences contribute to species-specific phenotypes. To investigate these questions, we generated nucleotide-resolution whole-genome methylation maps of the prefrontal cortex of multiple humans and chimpanzees. Levels and patterns of DNA methylation vary across individuals within species according to the age and the sex of the individuals. We also found extensive species-level divergence in patterns of DNA methylation and that hundreds of genes exhibit significantly lower levels of promoter methylation in the human brain than in the chimpanzee brain. Furthermore, we investigated the functional consequences of methylation differences in humans and chimpanzees by integrating data on gene expression generated with next-generation sequencing methods, and we found a strong relationship between differential methylation and gene expression. Finally, we found that differentially methylated genes are strikingly enriched with loci associated with neurological disorders, psychological disorders, and cancers. Our results demonstrate that differential DNA methylation might be an important molecular mechanism driving gene-expression divergence between human and chimpanzee brains and might potentially contribute to the evolution of disease vulnerabilities. Thus, comparative studies of humans and chimpanzees stand to identify key epigenomic modifications underlying the evolution of human-specific traits.

Original languageEnglish (US)
Pages (from-to)455-465
Number of pages11
JournalAmerican Journal of Human Genetics
Volume91
Issue number3
DOIs
StatePublished - Sep 7 2012

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Pan troglodytes
Epigenomics
Methylation
DNA Methylation
Genome
Brain
Gene Expression
Gene Expression Regulation
Prefrontal Cortex
Nervous System Diseases
Genes
Chromatin
Nucleotides
Psychology
Phenotype
DNA
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution. / Zeng, Jia; Konopka, Genevieve; Hunt, Brendan G.; Preuss, Todd M.; Geschwind, Dan; Yi, Soojin V.

In: American Journal of Human Genetics, Vol. 91, No. 3, 07.09.2012, p. 455-465.

Research output: Contribution to journalArticle

Zeng, Jia ; Konopka, Genevieve ; Hunt, Brendan G. ; Preuss, Todd M. ; Geschwind, Dan ; Yi, Soojin V. / Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution. In: American Journal of Human Genetics. 2012 ; Vol. 91, No. 3. pp. 455-465.
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