The Pendulum Model for Genome Compositional Dynamics: from the Four Nucleotides to the Twenty Amino Acids

The genetic code serves as one of the natural links for life’s two conceptual frameworks—the informational and operational tracks—bridging the nucleotide sequence of DNA and RNA to the amino acid sequence of protein and thus its structure and function. On the informational track, DNA and its four building blocks have four basic variables: order, length, GC and purine contents; the latter two exhibit unique characteristics in prokaryotic genomes where protein-coding sequences dominate. Bridging the two tracks, tRNAs and their aminoacyl tRNA synthases that interpret each codon—nucleotide triplet, together with ribosomes, form a complex machinery that translates genetic information encoded on the messenger RNAs into proteins. On the operational track, proteins are selected in a context of cellular and organismal functions constantly. The principle of such a functional selection is to minimize the damage caused by sequence alteration in a seemingly random fashion at the nucleotide level and its function-altering consequence at the protein level; the principle also suggests that there must be complex yet sophisticated mechanisms to protect molecular interactions and cellular processes for cells and organisms from the damage in addition to both immediate or short-term eliminations and long-term selections. The two-century study of selection at species and population levels has been leading a way to understand rules of inheritance and evolution at molecular levels along the informational track, while ribogenomics, epigenomics and other operationally-defined omics (such as the metabolite-centric metabolomics) have been ushering biologists into the new millennium along the operational track.