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Evidence supporting the one gene-one protein hypothesis has increased rapidly in the past ten years. The development of techniques for the analysis of the amino acid sequences of proteins and protein fragments (1, 2) and mutational site sequences in genes (3, 4, 5) has opened the door to a direct experimental examination of the details of this relationship. In addition, the presentation of the Watson-Crick model of DNA (6) and the theoretical explorations of nucleotide coding (7 to 11) have provided a comforting theoretical background to questions of how the genetic material specifies the information essential for the assembling of the characteristic amino acid sequence of each protein. The experimental analysis of the precise mecha nism of cytoplasmic protein synthesis has led to an understanding of several major aspects of this process (see review by Novelli in this volume) .The previous history of the relationship of gene-to-protein has been re viewed in detail in recent papers (12, 13), and a list of some 50-odd examples of the effects of mutations on enzymes in 11 different organisms has been published within the last year (13). Therefore, the present paper will be con fined to a discussion of studies with well-analyzed gene-protein systems, and systems which show considerable promise for future investigation. Such studies are providing the gross information which will ultimately seek ex planation at the nucleotide and amino acid level. The discussion will be re stricted for the most part to microbial material. However, the mammalian hemoglobin system will also be discussed since it is proving to be a model for expectations and predictions of the effects of mutations on specific proteins. No attempt has been made to cover every paper on each subject but only those pertinent to the points discussed. In areas related to the main topics considered, general review articles are given as references.The word "gene" assumes different meanings according to the operations used in characterizing it (3). In this review the terms "gene" or "locus" will refer to a segment of the genetic material carrying the information for the 1 The survey of the literature pertaining to this review was concluded in February, 1960. 2 The following abbreviations will be used: CRM (cross-reacting material); DNA (deoxyribonubleic acid); RNA (ribonucleic acid); TPN (triphosphopyridine nucleo tide).

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