CROTCHETS & QUIDDITIES “The” Genetic Code?

Evolution and the diversification of organisms are made possible by codes, or arbitrary assignments of “meaning,” in multiple ways. Many are not widely appreciated. Codes allow the same system of components to be used for multiple purposes. These can be open-ended, the way the alphabet and vocabulary make this column possible, but the flexibility of a code can become constrained once a system with many components that must work in concert, if an organism is to develop and survive—or evolve— is in place. Codes are highly efficient ways to carry uncorrupted information from one place to enable indirect action elsewhere. But this requires a decryption system at the receiving end. Fidelity at both ends is vital. In World War II, the Germans had their Enigma encryption machine, whose use by U-boats caused chaos for British shipping, until the eccentric computer pioneer Alan Turing learned how to break the code. That led to doom for Germany. For organisms, the price for code breakdown in the Battle of Life is similarly unremorseful. Everyone knows of “the” genetic code, by which nucleotide triplets in DNA in the nucleus of cells specify the amino acid (aa) sequence of proteins. This is the code described in textbooks as the heart of the genetic theory of life and its evolution. Discoveries in recent years have made things more complicated by showing that genomes are littered with all sorts of other kinds of coding elements. An example is DNA sequences located near to protein-coding segments—“genes” proper—that are chemically recognized by regulatory proteins, which bind there to cause the nearby gene to be expressed (or repressed) in specific cells or under specific conditions.1,2 This gene-expression mechanism is as fundamental as the classical genetic code, because it allows cells to differentiate into organs and tissues, enabling organisms from plants to people to exist. The cells in the eyes you’re reading with and in the fingers that hold this page all have the same genome, but eyes and fingers are different because they use different subsets of those genes. This is specified by tissue-specific developmental codes. Other DNA sequence elements are used to package, protect, or copy DNA. Embryos develop and adult organisms respond to their environments by using extensive arbitrary codes in the form of combinations of chemical signaling molecules that are produced by specific genes and are released to be detected by other cells whose gene expression they alter. These are codes because it is the combination of factors, not the factors themselves, that carry the information. Your life depends on the fidelity of these many codes. Aberrant codes related to cell behavior can lead to dysgenesis or various metabolic diseases. Anomalous cell-surface proteins can cause autoimmune destruction, and viruses are the Alan Turings of life that evolve ways to break their receptor codes to gain illicit entry into cells (Fig. 1). But there is an additional code, a code of codes, that makes all of this possible, including “the” genetic code itself, and may be the oldest and most fundamental one of all. Protein-coding (Figure 2) works via two intermediaries: messenger RNA (mRNA), a complementary copy of code transcribed from a coding region of DNA, and transfer RNA (tRNA), which carries aa’s to ribosomes to be linked together to form a chain (polypeptide) that becomes a protein, thus translating “the” genetic code. If mRNA takes a message to ribosomes, tRNA is the Enigma decrypter that turns the code into action (a protein). As important as the genetic protein code itself is, this decryption system may be the most deeply fundamental aspect of the coding system, itself a kind of code, and probably the first code. In 1953 Watson and Crick solved the basic structure of DNA as a set of parallel chains connected by specific pairing of nucleotides, A with T and C with G, the famous double helix. It was not until 1967 that the use of DNA to code for aa sequences—our friend the protein code, shown in Table 1—was deciphered (see3). Remarkably, this protein-coding process was found to be based on the same Watson-Crick complementary basepairing phenomenon that made DNA itself. Experiments that synthesized Ken Weiss is Evan Pugh Professor and Anne Buchanan is Senior Research Scientist in the Department of Anthropology at Penn State University. E-mail: [email protected]