Dynamics of DNA Methylation in Recent Human and Great Ape Evolution

Abstract

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 disease. However, the dynamics of DNA methylation changes between humans and their closest relatives are still poorly understood. We performed a comparative analysis of CpG methylation patterns between 9 humans and 23 primate samples including all species of great apes (chimpanzee, bonobo, gorilla and orangutan) using Illumina Methylation450 bead arrays. Our analysis identified ∼800 genes with significantly altered methylation patterns among the great apes, including ∼170 genes with a methylation pattern unique to human. Some of these are known to be involved in developmental and neurological features, suggesting that epigenetic changes have been frequent during recent human and primate evolution. We identified a significant positive relationship between the rate of coding variation and alterations of methylation at the promoter level, indicative of co-occurrence between evolution of protein sequence and gene regulation. In contrast, and supporting the idea that many phenotypic differences between humans and great apes are not due to amino acid differences, our analysis also identified 184 genes that are perfectly conserved at protein level between human and chimpanzee, yet show significant epigenetic differences between these two species. We conclude that epigenetic alterations are an important force during primate evolution and have been under-explored in evolutionary comparative genomics.

Recently evolved human-specific methylated regions are enriched in schizophrenia signals

“…The enrichment seen for schizophrenia also corroborates the results of Gokhman et al (28) who reported that DMRs were more enriched around genes implicated in the nervous system amongst all the organ systems tested for evolutionary changes in methylation patterns. Hernando-Herraez et al (40) also found that methylation differences between humans and great apes were located around genes controlling neurological and developmental features. It is therefore possible that the methylation differences were mediated by evolution of genomic regions controlling neurodevelopmental processes.…”

“…Furthermore, while the DMRs utilized here were obtained from bone samples, the authors of the original study (28) referred to the report by HernandoHerraez et al (40) which demonstrated that species-specific DMRs tend to be conserved across tissues and as such should not represent tissue-specific variations. Other studies also showed that neurological systems were enriched for methylation differences even when the tissue samples analyzed were not neurological (41)(42)(43).…”

Distinct Copy Number, Coding Sequence, and Locus Methylation Patterns UnderlieRhg1-Mediated Soybean Resistance to Soybean Cyst Nematode

“…Epigenetic modifications, prominently including differential cytosine methylation, can also significantly impact organismal phenotypes (Chen, 2007;Gohlke et al, 2013;Hernando-Herraez et al, 2013). While the term epigenetic indicates heritable changes in gene activity not caused by changes in DNA sequence, there is increasing appreciation not only of the extent of methylation and other epigenetic marks throughout genomes, but also of the plasticity of these marks (Schmitz et al, 2013b;Ziller et al, 2013).…”

Insights in human epigenomic dynamics through comparative primate analysis

“…Known variation can help excluding probes, however non-human primate polymorphic information is less complete. An inter-primate analysis was performed with the Illumina 450k DNA methylation array in peripheral blood [83]. Only less than a quarter of the probes (99,919) were assessed as complementary across five primate species, with 289,007 shared between human and chimpanzee.…”