title: Three periods of regulatory innovation during vertebrate evolution.
abstract: The gain, loss, and modification of gene regulatory elements may underlie a substantial proportion of phenotypic changes on animal lineages. To investigate the gain of regulatory elements throughout vertebrate evolution, we identified genome-wide sets of putative regulatory regions for five vertebrates, including humans. These putative regulatory regions are conserved nonexonic elements (CNEEs), which are evolutionarily conserved yet do not overlap any coding or noncoding mature transcript. We then inferred the branch on which each CNEE came under selective constraint. Our analysis identified three extended periods in the evolution of gene regulatory elements. Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers.
authors.affiliation: Center for Biomolecular Science and Engineering, University of California, Santa Cruz, CA 95064, USA.
authors.forename: Craig B
authors.initials: CB
authors.lastname: Lowe
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.forename: Adam
authors.initials: A
authors.lastname: Siepel
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Raney
authors.forename: Michele
authors.initials: M
authors.lastname: Clamp
authors.forename: Sofie R
authors.initials: SR
authors.lastname: Salama
authors.forename: David M
authors.initials: DM
authors.lastname: Kingsley
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
authors.forename: David
authors.initials: D
authors.lastname: Haussler
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002417:Cattle; D017124:Conserved Sequence; D021901:DNA, Intergenic / Q000235:genetics; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D050437:Genes, Developmental; D016678:Genome; D006801:Humans; D008390:Markov Chains; D051379:Mice; D009990:Oryzias / Q000235:genetics; D010802:Phylogeny; D011499:Protein Processing, Post-Translational / Q000235:genetics; D050436:Regulatory Elements, Transcriptional; D012045:Regulatory Sequences, Nucleic Acid; D012641:Selection, Genetic; D016415:Sequence Alignment; D023701:Smegmamorpha / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014714:Vertebrates / Q000235:genetics*
chemical_list: D021901:DNA, Intergenic; D014157:Transcription Factors