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.
More...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.
Overall design: 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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