title: The interplay between DNA methylation and sequence divergence in recent human evolution.
abstract: Despite the increasing knowledge about DNA methylation, the understanding of human epigenome evolution is in its infancy. Using whole genome bisulfite sequencing we identified hundreds of differentially methylated regions (DMRs) in humans compared to non-human primates and estimated that ∼25% of these regions were detectable throughout several human tissues. Human DMRs were enriched for specific histone modifications and the majority were located distal to transcription start sites, highlighting the importance of regions outside the direct regulatory context. We also found a significant excess of endogenous retrovirus elements in human-specific hypomethylated.We reported for the first time a close interplay between inter-species genetic and epigenetic variation in regions of incomplete lineage sorting, transcription factor binding sites and human differentially hypermethylated regions. Specifically, we observed an excess of human-specific substitutions in transcription factor binding sites located within human DMRs, suggesting that alteration of regulatory motifs underlies some human-specific methylation patterns. We also found that the acquisition of DNA hypermethylation in the human lineage is frequently coupled with a rapid evolution at nucleotide level in the neighborhood of these CpG sites. Taken together, our results reveal new insights into the mechanistic basis of human-specific DNA methylation patterns and the interpretation of inter-species non-coding variation.
authors.affiliation: Institute of Evolutionary Biology (UPF-CSIC), PRBB, 08003 Barcelona, Spain irene.hernando@upf.edu.
authors.forename: Irene
authors.initials: I
authors.lastname: Hernando-Herraez
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Holger
authors.initials: H
authors.lastname: Heyn
authors.affiliation: Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona, Barcelona 08028, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Fernandez-Callejo
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Vidal
authors.affiliation: Parc Zoològic de Barcelona, Parc de la Ciutadella s/n, Barcelona 08003, Spain.
authors.forename: Hugo
authors.initials: H
authors.lastname: Fernandez-Bellon
authors.affiliation: Institute of Evolutionary Biology (UPF-CSIC), PRBB, 08003 Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Prado-Martinez
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai School, New York, NY 10029, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sharp
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Spain Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain mesteller@idibell.cat.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.affiliation: Institute of Evolutionary Biology (UPF-CSIC), PRBB, 08003 Barcelona, Spain Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona, Barcelona 08028, Spain Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain tomas.marques@upf.edu.
authors.forename: Tomas
authors.initials: T
authors.lastname: Marques-Bonet
mesh_terms: D000818:Animals; D019175:DNA Methylation; D019143:Evolution, Molecular; D014644:Genetic Variation; D023281:Genomics; D006071:Gorilla gorilla; D006801:Humans; D002679:Pan troglodytes; D057080:Pongo abelii; D017422:Sequence Analysis, DNA; D013045:Species Specificity