Unknown,Transcriptomics,Genomics,Proteomics

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A Genome-wide Study of DNA Methylation Patterns and Gene Expression Levels in Multiple Human and Chimpanzee Tissues

ABSTRACT: It has long been hypothesized that changes in gene regulation have played an important role in primate evolution. However, despite the wealth of comparative gene expression data, there are still only few studies that focus on the mechanisms underlying inter-primate differences in gene regulation. In particular, we know relatively little about the degree to which changes in epigenetic profiles might explain differences in gene expression levels between primates. To this end, we studied DNA methylation and gene expression levels in livers, hearts, and kidneys from multiple humans and chimpanzees. Genome wide DNA methylation profiling of heart, kidney, and liver samples from humans and chimpanzees. The Illumina Infinium 27K Human DNA Methylation BeadChip v1.2 was used to compare DNA methylation profiles across approximately 10,575 CpG sites in human and chimpanzee tissue samples. Samples included 6 human livers, 6 human kidneys, 6 human heart, 6 chimpanzee livers, 6 chimpanzee kidneys, and 6 chimpanzee hearts. Two techical replicates of bisulfite converted DNA from each of the 36 samples was hybridized to the Illumina HumanMethylation27 Beadchip. We limited our analysis to the 10,575 probes that were a perfect sequence match to both the human and chimpanzee genomes and which were associated with genes for which we had previously collected expression measurements across the three tissues.

ORGANISM(S): Pan troglodytes

SUBMITTER: Athma Pai

PROVIDER: E-GEOD-26033 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:DNA methylation is an epigenetic modification involved in regulatory processes such as cell differentiation during development, X-chromosome inactivation, genomic imprinting and susceptibility to complex diseases. These changes can be inherited through generations and likely have played an important role during human evolution. We performed a comparative analysis of CpG methylation patterns between humans and all great apes (chimpanzee, bonobo, gorilla and orangutan) on a total of 32 individuals.Our analysis identified ~1,000 genes with significantly altered methylation patterns among the great apes, including ~200 with a methylation pattern unique to humans. Analysis of genes with human-specific epigenetic patterns identified enrichments for several functional categories that are key for human-specific traits, such as advanced facial expressions or equilibrium related to bipedalism. We also found a highly significant positive correlation between the genomic distance genome-wide and the methylation levels. In a pairwise comparison, we observed that ~9% (~30,000) of CpGs assayed show significant methylation differences between human and chimpanzee, including promoter regions of 879 genes (11.9% of those tested), suggesting that epigenetic changes have occurred at high frequency during recent primate evolution and represent an important substrate for adaptive modification of genome function. Epigenetic changes among primates are highly enriched for sites showing intermediate DNA methylation levels might be related to regulatory elements, and we observed a significant relationship between changes in DNA methylation and gene expression across multiple different tissues. We also identified a significant positive relationship between the rate of coding variation within genes and alterations of promoter methylation, suggesting concerted evolution between protein sequence and gene regulation. Contrastingly, our analysis also identified scores of genes that are perfectly conserved at the amino acid level between human and chimp, yet which show significant epigenetic difference between these two species. We conclude that epigenetic alterations represent an important force during primate evolution and has been systematically under explored in evolutionary comparative genomics. 32 samples analyzed in total: 9 humans, 5 chimpanzees, 6 bonobos, 6 gorillas and 6 orangutans. Blood-derived DNA methylation levels were assessed using Illumina Infinium HumanMethylation450 BeadChip. We performed a strict filtering step to remove divergent probes based on the number and location of mismatches with their target site in each species genome assembly tested, this resulted in the retention of 133,908 shared across all the species.

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A Genome-wide Study of DNA Methylation Patterns and Gene Expression Levels in Multiple Human and Chimpanzee Tissues

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