Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution.
How do epigenetic modifications change across species and how do these modifications affect evolution? These are fundamental questions at the forefront of our evolutionary epigenomic understanding. Our previous work investigated human and chimpanzee brain methylomes, but it was limited by the lack of outgroup data which is critical for comparative (epi)genomic studies. Here, we compared whole genome DNA methylation maps from brains of humans, chimpanzees and also rhesus macaques (outgroup) to elucidate DNA methylation changes during human brain evolution. Moreover, we validated that our approach is highly robust by further examining 38 human-specific DMRs using targeted deep genomic and bisulfite sequencing in an independent panel of 37 individuals from five primate species. Our unbiased genome-scan identified human brain differentially methylated regions (DMRs), irrespective of their associations with annotated genes. Remarkably, over half of the newly identified DMRs locate in intergenic regions or gene bodies. Nevertheless, their regulatory potential is on par with those of promoter DMRs. An intriguing observation is that DMRs are enriched in active chromatin loops, suggesting human-specific evolutionary remodeling at a higher-order chromatin structure. These findings indicate that there is substantial reprogramming of epigenomic landscapes during human brain evolution involving noncoding regions.
School of Biological Sciences, Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, Leioa, Spain. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI. School of Biological Sciences, Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA. Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX. Division of Neuropharmacology and Neurologic Diseases & Center for Translational Social Neuroscience, Department of Pathology and Laboratory Medicine, Yerkes National Primate Research Center, Emory University School of Medicine, Emory University, Atlanta, GA. Department of Plant and Microbial Biology and Plants for Human Health Institute, North Carolina State University, Raleigh, NC. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China soojinyi@gatech.edu sub@mail.kiz.ac.cn. School of Biological Sciences, Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA soojinyi@gatech.edu sub@mail.kiz.ac.cn.
