Raising the estimate of functional human sequences

Pheasant, M. and Mattick, J. S. (2007) Raising the estimate of functional human sequences. Genome Research, 17 9: 1245-1253. doi:10.1101/gr.6406307

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Author Pheasant, M.
Mattick, J. S.
Title Raising the estimate of functional human sequences
Journal name Genome Research   Check publisher's open access policy
ISSN 1088-9051
Publication date 2007
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1101/gr.6406307
Open Access Status File (Publisher version)
Volume 17
Issue 9
Start page 1245
End page 1253
Total pages 9
Editor Hillary E. Sussman
Place of publication Cold Spring Harbor, NY, United States
Publisher Cold Spring Harbour Lab Press
Collection year 2008
Language eng
Abstract While less than 1.5% of the mammalian genome encodes proteins, it is now evident that the vast majority is transcribed, mainly into non-protein-coding RNAs. This raises the question of what fraction of the genome is functional, i.e., composed of sequences that yield functional products, are required for the expression (regulation or processing) of these products, or are required for chromosome replication and maintenance. Many of the observed noncoding transcripts are differentially expressed, and, while most have not yet been studied, increasing numbers are being shown to be functional and/or trafficked to specific subcellular locations, as well as exhibit subtle evidence of selection. On the other hand, analyses of conservation patterns indicate that only similar to 5% (3%-8%) of the human genome is under purifying selection for functions common to mammals. However, these estimates rely on the assumption that reference sequences (usually ancient transposon-derived sequences) have evolved neutrally, which may not be the case, and if so would lead to an underestimate of the fraction of the genome under evolutionary constraint. These analyses also do not detect functional sequences that are evolving rapidly and/or have acquired lineage-specific functions. Indeed, many regulatory sequences and known functional noncoding RNAs, including many microRNAs, are not conserved over significant evolutionary distances, and recent evidence from the ENCODE project suggests that many functional elements show no detectable level of sequence constraint. Thus, it is likely that much more than 5% of the genome encodes functional information, and although the upper bound is unknown, it may be considerably higher than currently thought.
Keyword Biochemistry & Molecular Biology
Biotechnology & Applied Microbiology
Genetics & Heredity
Polymerase-ii Transcription
Protein-coding Genes
Transposable Elements
Human Genome
Noncoding Rnas
Mammalian Genomes
Alu Elements
Rapid Evolution
Host Genes
Regulatory Elements
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Excellence in Research Australia (ERA) - Collection
2008 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 148 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 157 times in Scopus Article | Citations
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Created: Mon, 21 Apr 2008, 15:28:32 EST by Jennifer Greder on behalf of Institute for Molecular Bioscience