Genetic

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What is a gene, post-ENCODE? History and updated definition
Mark B. Gerstein, Can Bruce, Joel S. Rozowsky, et al. Genome Res. 2007 17: 669-681 Access the most recent version at doi:10.1101/gr.6339607

Supplemental Material Referenceshttp://genome.cshlp.org/content/suppl/2007/05/29/17.6.669.DC1.html This article cites 99 articles, 42 of which can be accessed free at: http://genome.cshlp.org/content/17/6/669.full.html#ref-list-1 Article cited in: http://genome.cshlp.org/content/17/6/669.full.html#related-urls

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Freely available online through the Genome Research Open Access option. Origin of phenotypes: Genes and transcripts Thomas R. Gingeras GenomeRes. June , 2007 17: 682-690 Raising the estimate of functional human sequences Michael Pheasant and John S. Mattick Genome Res. September , 2007 17: 1245-1253

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Downloaded from genome.cshlp.org on May 30, 2011 - Published by Cold Spring Harbor Laboratory Press

Perspective

What is a gene, post-ENCODE? History and updated definition
Mark B. Gerstein,1,2,3,9 Can Bruce,2,4 Joel S. Rozowsky,2 Deyou Zheng,2 Jiang Du,3 Jan O. Korbel,2,5 Olof Emanuelsson,6 Zhengdong D. Zhang,2 ShermanWeissman,7 and Michael Snyder2,8
Program in Computational Biology & Bioinformatics, Yale University, New Haven, Connecticut 06511, USA; 2Molecular Biophysics & Biochemistry Department, Yale University, New Haven, Connecticut 06511, USA; 3Computer Science Department, Yale University, New Haven, Connecticut 06511, USA; 4Center for Medical Informatics, Yale University, New Haven, Connecticut 06511, USA;5European Molecular Biology Laboratory, 69117 Heidelberg, Germany; 6Stockholm Bioinformatics Center, Albanova University Center, Stockholm University, SE-10691 Stockholm, Sweden; 7Genetics Department, Yale University, New Haven, Connecticut 06511, USA; 8Molecular, Cellular, & Developmental Biology Department, Yale University, New Haven, Connecticut 06511, USA While sequencing of the human genomesurprised us with how many protein-coding genes there are, it did not fundamentally change our perspective on what a gene is. In contrast, the complex patterns of dispersed regulation and pervasive transcription uncovered by the ENCODE project, together with non-genic conservation and the abundance of noncoding RNA genes, have challenged the notion of the gene. To illustrate this, we review theevolution of operational definitions of a gene over the past century—from the abstract elements of heredity of Mendel and Morgan to the present-day ORFs enumerated in the sequence databanks. We then summarize the current ENCODE findings and provide a computational metaphor for the complexity. Finally, we propose a tentative update to the definition of a gene: A gene is a union of genomic sequencesencoding a coherent set of potentially overlapping functional products. Our definition sidesteps the complexities of regulation and transcription by removing the former altogether from the definition and arguing that final, functional gene products (rather than intermediate transcripts) should be used to group together entities associated with a single gene. It also manifests how integral the conceptof biological function is in defining genes.
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Introduction
The classical view of a gene as a discrete element in the genome has been shaken by ENCODE
The ENCODE consortium recently completed its characterization of 1% of the human genome by various high-throughput experimental and computational techniques designed to characterize functional elements (The ENCODE Project Consortium 2007)....