How many periods of regulatory innovation led to the evolution of vertebrates?
['Three periods of regulatory innovation during vertebrate evolution.', '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.', '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.', 'Our analysis identified three extended periods in the evolution of gene regulatory elements. ', '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.', '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.', '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.', '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.']
['Investigators proposed that there have been 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.']
['Three']