What is a gene, post-ENCODE? History and updated definition

Mark B. Gerstein, Can Bruce, Joel S. Rozowsky, Deyou Zheng, Jiang Du, Jan O. Korbel, Olof Emanuelsson, Zhengdong Zhang, Sherman Weissman, Michael Snyder

Research output: Contribution to journalArticle

403 Citations (Scopus)

Abstract

While sequencing of the human genome surprised 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 the evolution 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 sequences encoding 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 concept of biological function is in defining genes.

Original languageEnglish (US)
Pages (from-to)669-681
Number of pages13
JournalGenome Research
Volume17
Issue number6
DOIs
StatePublished - Jun 2007
Externally publishedYes

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History
Genes
Untranslated RNA
Metaphor
Heredity
Human Genome
Open Reading Frames
Databases
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Gerstein, M. B., Bruce, C., Rozowsky, J. S., Zheng, D., Du, J., Korbel, J. O., ... Snyder, M. (2007). What is a gene, post-ENCODE? History and updated definition. Genome Research, 17(6), 669-681. https://doi.org/10.1101/gr.6339607

What is a gene, post-ENCODE? History and updated definition. / Gerstein, Mark B.; Bruce, Can; Rozowsky, Joel S.; Zheng, Deyou; Du, Jiang; Korbel, Jan O.; Emanuelsson, Olof; Zhang, Zhengdong; Weissman, Sherman; Snyder, Michael.

In: Genome Research, Vol. 17, No. 6, 06.2007, p. 669-681.

Research output: Contribution to journalArticle

Gerstein, MB, Bruce, C, Rozowsky, JS, Zheng, D, Du, J, Korbel, JO, Emanuelsson, O, Zhang, Z, Weissman, S & Snyder, M 2007, 'What is a gene, post-ENCODE? History and updated definition', Genome Research, vol. 17, no. 6, pp. 669-681. https://doi.org/10.1101/gr.6339607
Gerstein MB, Bruce C, Rozowsky JS, Zheng D, Du J, Korbel JO et al. What is a gene, post-ENCODE? History and updated definition. Genome Research. 2007 Jun;17(6):669-681. https://doi.org/10.1101/gr.6339607
Gerstein, Mark B. ; Bruce, Can ; Rozowsky, Joel S. ; Zheng, Deyou ; Du, Jiang ; Korbel, Jan O. ; Emanuelsson, Olof ; Zhang, Zhengdong ; Weissman, Sherman ; Snyder, Michael. / What is a gene, post-ENCODE? History and updated definition. In: Genome Research. 2007 ; Vol. 17, No. 6. pp. 669-681.
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