title: Relative codon adaptation: a generic codon bias index for prediction of gene expression.
abstract: The development of codon bias indices (CBIs) remains an active field of research due to their myriad applications in computational biology. Recently, the relative codon usage bias (RCBS) was introduced as a novel CBI able to estimate codon bias without using a reference set. The results of this new index when applied to Escherichia coli and Saccharomyces cerevisiae led the authors of the original publications to conclude that natural selection favours higher expression and enhanced codon usage optimization in short genes. Here, we show that this conclusion was flawed and based on the systematic oversight of an intrinsic bias for short sequences in the RCBS index and of biases in the small data sets used for validation in E. coli. Furthermore, we reveal that how the RCBS can be corrected to produce useful results and how its underlying principle, which we here term relative codon adaptation (RCA), can be made into a powerful reference-set-based index that directly takes into account the genomic base composition. Finally, we show that RCA outperforms the codon adaptation index (CAI) as a predictor of gene expression when operating on the CAI reference set and that this improvement is significantly larger when analysing genomes with high mutational bias.
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County (UMBC), 1000 Hilltop Road, Baltimore, MD 21228, USA.
authors.forename: Jesse M
authors.initials: JM
authors.lastname: Fox
authors.forename: Ivan
authors.initials: I
authors.lastname: Erill
mesh_terms: D001419:Bacteria / Q000235:genetics*; D001482:Base Composition; D015415:Biomarkers / Q000378:metabolism; D003062:Codon; D019295:Computational Biology; D015870:Gene Expression; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D015415:Biomarkers; D003062:Codon
references.citation: FEBS Lett. 1991 Jul 22;285(2):165-9
references.pmid: 1855585
references.citation: BMC Genomics. 2008 Feb 27;9:102
references.pmid: 18304323
references.citation: Nucleic Acids Res. 1987 Feb 11;15(3):1281-95
references.pmid: 3547335
references.citation: Mol Biol Evol. 2005 Mar;22(3):547-61
references.pmid: 15537809
references.citation: Nucleic Acids Res. 1994 Jul 11;22(13):2437-46
references.pmid: 8041603
references.citation: J Bacteriol. 2001 Sep;183(17):5025-40
references.pmid: 11489855
references.citation: Genome Res. 2004 Nov;14(11):2279-86
references.pmid: 15479947
references.citation: J Mol Biol. 1997 Apr 25;268(1):78-94
references.pmid: 9149143
references.citation: Comput Appl Biosci. 1996 Apr;12(2):135-43
references.pmid: 8744776
references.citation: Mol Biol Evol. 2007 Feb;24(2):374-81
references.pmid: 17101719
references.citation: Mol Biol Evol. 1988 Nov;5(6):704-16
references.pmid: 3146682
references.citation: Mol Biol Evol. 2002 Aug;19(8):1390-4
references.pmid: 12140252
references.citation: Mol Cell Biol. 1999 Nov;19(11):7357-68
references.pmid: 10523624
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):60-4
references.pmid: 10592181
references.citation: Mol Biol Evol. 1985 Jan;2(1):13-34
references.pmid: 3916708
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W126-31
references.pmid: 17439967
references.citation: Biochem J. 1979 Feb 15;178(2):305-12
references.pmid: 36075
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13004-9
references.pmid: 16916930
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D866-70
references.pmid: 17932051
references.citation: Bioinformatics. 2003 Nov 1;19(16):2005-15
references.pmid: 14594704
references.citation: J Mol Biol. 1997 Jul 25;270(4):544-50
references.pmid: 9245585
references.citation: J Biol Chem. 1975 May 25;250(10):4007-21
references.pmid: 236308
references.citation: Appl Environ Microbiol. 2006 Oct;72(10):6841-4
references.pmid: 17021241
references.citation: Gene. 1982 Jun;18(3):199-209
references.pmid: 6751939
references.citation: Mol Biol Evol. 1996 Jul;13(6):864-72
references.pmid: 8754221
references.citation: Gene. 1998 Jul 30;215(2):405-13
references.pmid: 9714839
references.citation: Bioinformatics. 2009 Jun 1;25(11):1397-403
references.pmid: 19318424
references.citation: Nucleic Acids Res. 2003 Feb 15;31(4):e15
references.pmid: 12582260
references.citation: Gene. 2009 Aug 15;443(1-2):121-31
references.pmid: 19410638
references.citation: J Biol Chem. 1982 Mar 25;257(6):3026-31
references.pmid: 7037777
references.citation: Curr Issues Mol Biol. 2001 Oct;3(4):91-7
references.pmid: 11719972
references.citation: Yeast. 2004 Oct 15;21(13):1083-93
references.pmid: 15484285
references.citation: Genome Biol. 2002 Jul 31;3(8):COMMENT2008
references.pmid: 12186637
references.citation: Nucleic Acids Res. 1999 Oct 1;27(19):3821-35
references.pmid: 10481021
references.citation: Nucleic Acids Res. 2003 Dec 1;31(23):6976-85
references.pmid: 14627830
references.citation: Gene. 1990 Mar 1;87(1):23-9
references.pmid: 2110097
references.citation: Microbiology (Reading). 2000 Apr;146 ( Pt 4):851-860
references.pmid: 10784043
references.citation: Yeast. 2000 Sep 15;16(12):1131-45
references.pmid: 10953085
references.citation: Genome Res. 2005 Aug;15(8):1118-26
references.pmid: 16077011
references.citation: BMC Bioinformatics. 2005 Jul 19;6:182
references.pmid: 16029499
references.citation: Trends Biotechnol. 2004 Jul;22(7):346-53
references.pmid: 15245907
references.citation: J Mol Evol. 1998 Sep;47(3):268-74
references.pmid: 9732453
references.citation: Annu Rev Genet. 1998;32:185-225
references.pmid: 9928479
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: Methods Mol Biol. 2009;532:215-25
references.pmid: 19271187
references.citation: DNA Res. 2009 Feb;16(1):13-30
references.pmid: 19131380
references.citation: J Bacteriol. 1999 Oct;181(20):6425-40
references.pmid: 10515934
references.citation: Nucleic Acids Res. 2003 Apr 15;31(8):2242-51
references.pmid: 12682375