Correlation between sequence conservation of the 5 ' untranslated region and codon usage bias in Mus musculus genes

The codon adaptation index (CAI) values of all protein-coding sequences of the full-length cDNA libraries of Mus musculus were computed based on the R IKEN mouse full-length cDNA library. We have also computed the extent of co nsensus in flanking sequences of the initiator ATG codon based on the 'rela tive entropy' values of respective nucleotide positions (from - 20 to + 12 bp relative to the initiator ATG codon) for each group of genes classified by CAI values. With regard to the two nucleotides positions (-3 and +4) kno wn to be highly conserved in Kozak's consensus sequence, a clear correlatio n between CAI values and relative entropy values was observed at position - 3 but this was not significant at position +4, although a significant corre lation was found at position - I of the consensus sequence. Further, althou gh no correlation was observed at any additional positions, relative entrop y values were very high at positions -4, -6, and -8 in genes with high CAI values. These findings suggest that the extent of conservation in the flank ing sequence of the initiator ATG codon including Kozak's consensus sequenc e was an important factor in modulation of the translation efficiency as we ll as synonymous codon usage bias particularly in highly expressed genes. ( C) 2001 Published by Elsevier Science B.V.