Collinearity and the genetic code

Abstract

Modern knowledge of the mechanism of expression of genes derives from the idea, formulated by Beadle in 1945, that each gene determines the structure of a specific protein At that time, this was all that could be said since very little was known about the chemical structure of genes and proteins and nothing about their synthesis Although deoxyribonucleic acid ( DNA ) had been recognized as a component of chromosomes for many years, there was great reluctance to ascribe all the properties of the genetic material to it. Many geneticists felt the need to postulate that proteins would be an essential part of the structure of a gene, because, at that time, proteins were the only molecules known to possess a wide range of chemical specificities. Indeed, the distinction between genes and enzymes was often blurred, and there were many proponents of the idea that a gene was a special, autosynthetic enzyme. All of these ideas were exploded by Avery's experiments which proved beyond doubt that DNA was the carrier of genetic information. Genes and their products were thus shown to be chemically different, and the precise relationship between nucleic acids and proteins became the central question of genetics. The most important development in our understanding of this problem was the discovery of the structure of DNA by Watson & Crick in 1953. In this structure, two polynucleotide chains are wound around each other and held together by hydrogen bonds between specific pairs of bases: adenine with thymine and guanine with cytosine. This complementary feature of the structure immediately suggested how DNA could be replicated and the mechanism proposed by Watson & Crick has since been confirmed by many experiments. I t also became clear that the specificity of any piece of DNA had to be carried by its nucleotide sequence since the backbone is the same everywhere along the molecule. It is this sequence which has to be translated into protein structure. Proteins have a complicated threedimensional structure and there can be no doubt that the function of a protein depends on this structure. How can the information present in a one-dimensional nucleotide sequence of a gene be used to mould these elaborate structures? This formidable problem was solved by a hypothesis of extreme simplicity. Each protein is bult up of a simpler structure, the polypeptide chain. This contains a repeating backbone to which are attached the residues of the amino acids. And each polypeptide has a unique chemical structure given by its amino acid sequence. The ‘sequence hypothesis’ (Crick 1958) states that the gene specifies this amino acid sequence, and that the amino acid sequence determines how the chain will fold to generate the three-dimensional structure. A simple congruence exists between the one-dimensional nucleotide sequence of a gene and the one-dimensional amino acid sequence of a protein. This hypothesis makes two predictions: (1) There will be a linear correspondence between the gene and the protein it determines (collinearity). (2) Each amino acid will be specified by a given set of nucleotides (the genetic code).