The Reality of Pervasive Transcription
Michael B. Clark1, Paulo P. Amaral1#, Felix J. Schlesinger2#,Marcel E. Dinger1, Ryan J. Taft1, John L. Rinn3, Chris P. Ponting4, Peter F. Stadler5, Kevin V. Morris6, Antonin Morillon7, Joel S. Rozowsky8, Mark B. Gerstein8, Claes Wahlestedt9, Yoshihide Hayashizaki10, Piero Carninci10,Thomas R. Gingeras2*, John S. Mattick1*
1 Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia, 2 Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America, 3Broad Institute, Cambridge, Massachusetts, United States of America, 4 MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, 5 Department of Computer Science, University of Leipzig, Leipzig, Germany, 6 Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California, United States of America, 7 Institut Curie, UMR3244-Pavillon Trouillet Rossignol, Paris, France, 8 Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, United States of America, 9 University of Miami, Miami, Florida, United States of America, 10 Omics Science Center, RIKEN Yokohama Institute, Tsurumi-ku, Yokohama, Kanagawa, Japan
Citation: Clark MB, Amaral PP, Schlesinger FJ, Dinger ME, Taft RJ, et al. (2011) The Reality of Pervasive Transcription. PLoS Biol 9(7): e1000625. doi:10.1371/journal.pbio.1000625
Academic Editor: Michael B. Eisen, University of California Berkeley, United States of America
Published: July 12, 2011
Copyright: © 2011 Clark et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the Australian Research Council and National Health and Medical Research Council (JSM), NHGRI (TRG, PC), NIH (KVM, MG), Japanese MEXT Research Grant for the RIKEN Omics Science Center (YH, PC), EU FP-7 (PFS), Damon Runyon, Smith, Merkin and Searle scholarships (JLR), and UK BBSRC, ERC and MRC (CPP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Tim Hughes and Harm van Bakel for unreservedly providing their data to us for analysis.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: PR, precision recall
* E-mail: j.mattick@uq.edu.au(JSM); gingeras@cshl.edu (TRG)
# These authors contributed equally to this work.
Summary
Current estimates indicate that only about 1.2% of the mammalian genome codes for amino acids in proteins. However, mounting evidence over the past decade has suggested that the vast majority of the genome is transcribed, well beyond the boundaries of known genes, a phenomenon known as pervasive transcription [1]. Challenging this view, an article published in PLoS Biology by van Bakel et al. concluded that “the genome is not as pervasively transcribed as previously reported” [2] and that the majority of the detected low-level transcription is due to technical artefacts and/or background biological noise. These conclusions attracted considerable publicity [3]–[6]. Here, we present an evaluation of the analysis and conclusions of van Bakel et al. compared to those of others and show that (1) the existence of pervasive transcription is supported by multiple independent techniques; (2) re-analysis of the van Bakel et al. tiling arrays shows that their results are atypical compared to those of ENCODE and lack independent validation; and (3) the RNA sequencing dataset used by van Bakel et al. suffered from insufficient sequencing depth and poor transcript assembly, compromising their ability to detect the less abundant transcripts outside of protein-coding genes. We conclude that the totality of the evidence strongly supports pervasive transcription of mammalian genomes, although the biological significance of many novel coding and noncoding transcripts remains to be explored.
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