Calculating and comparing codon usage values in rare disease genes highlights codon clustering with disease-and tissue- specific hierarchy
Fig 4
The 5 extremely biased codons, differentially used by Homo sapiens in DC vs NDC genes, and among tissues.
Left graphs (A, B, C, D, E) show the codon frequency on the x-axis and the number of genes that use that specific codon (with the frequency annotate in x-axis) on the y-axis. Right graphs (F, G, H, I, L) show CU values in all studied mammals on the x-axis and codon usage values in gene tissues on the y-axis. Five codons were the most differentially used in HSA, CGU (Arg), CCA (Pro), GAC (Asp), GAU (Asp), and GUA (Val). Pink bars indicate DC genes, blue bars indicate NDC genes. CGU (A, F) is the least frequently used codon in NDC muscle genes; CCA (B, G) is the least frequently used codon in DC muscle genes; GAC (C, H) is the most frequently used codon in DC skin genes; GAU (D, I) is the most frequently used codon in NDC skin genes; GUA (E, L) is the least frequently used codon in DC kidney genes. Comparing CU values of these 5 extremely biased codons between DC and NDC gene groups and across mammals, the trend toward a heavy codon extremization during evolution can be appreciated. During evolution, CGU and CCA became more used in DC muscle genes, GAC became more used in skin DC genes, while GAU became more used in skin NDC genes, and GUA became more used in NDC kidney genes. This suggests a codon type-specific, disease-driven CUB, apparently conserved across mammals.