title: Genome-Wide Identification of Regulatory Sequences Undergoing Accelerated Evolution in the Human Genome.
abstract: Accelerated evolution of regulatory sequence can alter the expression pattern of target genes, and cause phenotypic changes. In this study, we used DNase I hypersensitive sites (DHSs) to annotate putative regulatory sequences in the human genome, and conducted a genome-wide analysis of the effects of accelerated evolution on regulatory sequences. Working under the assumption that local ancient repeat elements of DHSs are under neutral evolution, we discovered that ∼0.44% of DHSs are under accelerated evolution (ace-DHSs). We found that ace-DHSs tend to be more active than background DHSs, and are strongly associated with epigenetic marks of active transcription. The target genes of ace-DHSs are significantly enriched in neuron-related functions, and their expression levels are positively selected in the human brain. Thus, these lines of evidences strongly suggest that accelerated evolution on regulatory sequences plays important role in the evolution of human-specific phenotypes.
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biostatistics and Computational Biology, School of Life Sciences, Fudan University, Shanghai, P.R. China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biostatistics and Computational Biology, School of Life Sciences, Fudan University, Shanghai, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biostatistics and Computational Biology, School of Life Sciences, Fudan University, Shanghai, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biostatistics and Computational Biology, School of Life Sciences, Fudan University, Shanghai, P.R. China Children's Hospital of Fudan University, Shanghai, P.R. China weidong.tian@fudan.edu.cn.
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
mesh_terms: D005075:Biological Evolution; D002843:Chromatin / Q000235:genetics; D030561:Databases, Nucleic Acid; D003850:Deoxyribonuclease I / Q000378:metabolism; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D010802:Phylogeny; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D002843:Chromatin; D003850:Deoxyribonuclease I
keywords: DHS; accelerated evolution; regulatory sequence.