Relative codon adaptation: a generic codon bias index for prediction of gene expression.
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.
Fox
Jesse M
JM
Department of Biological Sciences, University of Maryland Baltimore County (UMBC), 1000 Hilltop Road, Baltimore, MD 21228, USA.
Erill
Ivan
I
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
D015415:Biomarkers; D003062:Codon
FEBS Lett. 1991 Jul 22;285(2):165-9
1855585
BMC Genomics. 2008 Feb 27;9:102
18304323
Nucleic Acids Res. 1987 Feb 11;15(3):1281-95
3547335
Mol Biol Evol. 2005 Mar;22(3):547-61
15537809
Nucleic Acids Res. 1994 Jul 11;22(13):2437-46
8041603
J Bacteriol. 2001 Sep;183(17):5025-40
11489855
Genome Res. 2004 Nov;14(11):2279-86
15479947
J Mol Biol. 1997 Apr 25;268(1):78-94
9149143
Comput Appl Biosci. 1996 Apr;12(2):135-43
8744776
Mol Biol Evol. 2007 Feb;24(2):374-81
17101719
Mol Biol Evol. 1988 Nov;5(6):704-16
3146682
Mol Biol Evol. 2002 Aug;19(8):1390-4
12140252
Mol Cell Biol. 1999 Nov;19(11):7357-68
10523624
Nucleic Acids Res. 2000 Jan 1;28(1):60-4
10592181
Mol Biol Evol. 1985 Jan;2(1):13-34
3916708
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W126-31
17439967
Biochem J. 1979 Feb 15;178(2):305-12
36075
Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13004-9
16916930
Nucleic Acids Res. 2008 Jan;36(Database issue):D866-70
17932051
Bioinformatics. 2003 Nov 1;19(16):2005-15
14594704
J Mol Biol. 1997 Jul 25;270(4):544-50
9245585
J Biol Chem. 1975 May 25;250(10):4007-21
236308
Appl Environ Microbiol. 2006 Oct;72(10):6841-4
17021241
Gene. 1982 Jun;18(3):199-209
6751939
Mol Biol Evol. 1996 Jul;13(6):864-72
8754221
Gene. 1998 Jul 30;215(2):405-13
9714839
Bioinformatics. 2009 Jun 1;25(11):1397-403
19318424
Nucleic Acids Res. 2003 Feb 15;31(4):e15
12582260
Gene. 2009 Aug 15;443(1-2):121-31
19410638
J Biol Chem. 1982 Mar 25;257(6):3026-31
7037777
Curr Issues Mol Biol. 2001 Oct;3(4):91-7
11719972
Yeast. 2004 Oct 15;21(13):1083-93
15484285
Genome Biol. 2002 Jul 31;3(8):COMMENT2008
12186637
Nucleic Acids Res. 1999 Oct 1;27(19):3821-35
10481021
Nucleic Acids Res. 2003 Dec 1;31(23):6976-85
14627830
Gene. 1990 Mar 1;87(1):23-9
2110097
Microbiology (Reading). 2000 Apr;146 ( Pt 4):851-860
10784043
Yeast. 2000 Sep 15;16(12):1131-45
10953085
Genome Res. 2005 Aug;15(8):1118-26
16077011
BMC Bioinformatics. 2005 Jul 19;6:182
16029499
Trends Biotechnol. 2004 Jul;22(7):346-53
15245907
J Mol Evol. 1998 Sep;47(3):268-74
9732453
Annu Rev Genet. 1998;32:185-225
9928479
Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
9254694
Methods Mol Biol. 2009;532:215-25
19271187
DNA Res. 2009 Feb;16(1):13-30
19131380
J Bacteriol. 1999 Oct;181(20):6425-40
10515934
Nucleic Acids Res. 2003 Apr 15;31(8):2242-51
12682375