Correlation between nucleotide composition and folding energy of coding sequences with special attention to wobble bases.
BACKGROUND
The secondary structure and complexity of mRNA influences its accessibility to regulatory molecules (proteins, micro-RNAs), its stability and its level of expression. The mobile elements of the RNA sequence, the wobble bases, are expected to regulate the formation of structures encompassing coding sequences.


RESULTS
The sequence/folding energy (FE) relationship was studied by statistical, bioinformatic methods in 90 CDS containing 26,370 codons. I found that the FE (dG) associated with coding sequences is significant and negative (407 kcal/1000 bases, mean +/- S.E.M.) indicating that these sequences are able to form structures. However, the FE has only a small free component, less than 10% of the total. The contribution of the 1st and 3rd codon bases to the FE is larger than the contribution of the 2nd (central) bases. It is possible to achieve a approximately 4-fold change in FE by altering the wobble bases in synonymous codons. The sequence/FE relationship can be described with a simple algorithm, and the total FE can be predicted solely from the sequence composition of the nucleic acid. The contributions of different synonymous codons to the FE are additive and one codon cannot replace another. The accumulated contributions of synonymous codons of an amino acid to the total folding energy of an mRNA is strongly correlated to the relative amount of that amino acid in the translated protein.


CONCLUSIONS
Synonymous codons are not interchangable with regard to their role in determining the mRNA FE and the relative amounts of amino acids in the translated protein, even if they are indistinguishable in respect of amino acid coding.
Biro
Jan C
JC
Homulus Foundation, 612 S Flower Str,, #1220, Los Angeles, CA 90017, USA. jan.biro@att.net
D000465:Algorithms; D001482:Base Composition; D003062:Codon; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D006801:Humans; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry; D009711:Nucleotides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism
D003062:Codon; D009696:Nucleic Acids; D009711:Nucleotides; D011506:Proteins; D012333:RNA, Messenger; D012313:RNA