What is a gene, post-ENCODE? History and updated definition.
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 side-steps 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.
Gerstein
Mark B
MB
Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06511, USA. Mark.Gerstein@yale.edu
Bruce
Can
C
Rozowsky
Joel S
JS
Zheng
Deyou
D
Du
Jiang
J
Korbel
Jan O
JO
Emanuelsson
Olof
O
Zhang
Zhengdong D
ZD
Weissman
Sherman
S
Snyder
Michael
M
D002874:Chromosome Mapping / Q000266:history; D015894:Genome, Human; D049672:History, 19th Century; D049673:History, 20th Century; D049674:History, 21st Century; D016045:Human Genome Project / Q000266:history / Q000458:organization & administration; D006801:Humans; D016366:Open Reading Frames / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*
D022661:RNA, Untranslated