Bioinformatic Analysis Of Disease-Associated Alternative Splicing Genes And Codon-Complementary Codons

Genetic code is the biological language in communication between DNA and protein. To reveal the role of different usage of genetic codons and their complementary codons in the evolution of disease-associated alternative splicing, 118 alternatively spliced human genes with 2,903 nucleotide substitutions were statistically analyzed. It is found that nucleotide tranitions has overall preponderance over nucleotide transversions (60.11 % versus 39.89 %). The propobility of substituation in the first, second and third base of codons are 49.26 %, 42.16 % and 8.58 %, respectively. Among tri-nucleotides (triplets) formed by the substitutions (denoted as N) and their immediate neighboring nucleotides (5' to 3'), 1,866 (64.28 %) are of pyrimidine-N-purine or purine-N-purine types. Futher exon analysis of these disease-related genes found that single base substitutions are much denser within the first and last two exons than that of middle exons. 83.91 % of substitutions have occurred within exons that have a medium range (40 ~ 65 %) of GC content. Larger exons seem to have suffered fewer substitutions. Additional study of 44 cellular organisms, 16 viruses, 40 mitochondria and 20 chloroplasts indicates that there exist significant correlation between codons and corresponding complementary codons usage in species except virus. Moreover, phylogentic tree was generated based on this finding, which is comparable to traditional molecular evolution tree.