Analysis of correlation of local GC level in human protein coding genes

Abstract

GC level is an important feature of genomic composition, which significantly improve our understanding of structure, function and evolution of genes. In this paper, the nonredundant DNA sequence of 7,992 human protein coding genes were retrieved from public database and the local GC level of different sequence regions and correlation between GC levels were analyzed.. The results showed that the GC levels of different sequence regions were strikingly nonuniform. 5' untranslated regions were of richest GC, with average GC content being 62.5%. 3'-untranslated regions were of poorest GC, with average GC content being 43.97%. GC contents of 3' flanking sequences profoundly matched the GC levels of DNA large fragments where the genes were located. Although the GC contents of open reading frames (ORFs) were higher than that of intron, 3' non-translated region and 3' flanking sequences, high correlation existed among the GC contents of the four regions. Average GC content of the third codon position (GC3) was 58.9%, higher than that of the fist and second position, and showed high correlation to GC contents of ORFs, with correlation coefficients being 0.91, besides of its significant association with GC contents of intron, 3'-untranslated region and 3' flanking sequences. Moreover, the linear regression of GC3 against GC contents of 3' flanking sequences yielded a slope of 1.25. Thus, GC3 was a sensitive indicator for GC change of local genome. As for 5' flanking sequences, 5' untranslated regions, fist and second codon position, however, their GC level exhibited weaker correlation with that of other regions. These results suggest that the third codon positions, introns, 3'-untranslated regions and 3' flanking sequences may evolve similarly while first and second codon positions, 5' flanking sequences and 5' untranslated region were expected to bear more selective stress for holding their functions.