The Origin of Specific Proteins 97 



Hemoglobin, 1958). This is exactly what we have learned to expect 

 from the genetic control of protein synthesis; it tells us only that 

 primary protein structure is related directly to gene structure — pre- 

 sumably to the linear sequence of nucleotides that make up the DNA 

 molecule. Since the synthesis of hemoglobin occurs in the ribosomes 

 of the cytoplasm (Schweet et al., 1958) rather than on the chromo- 

 somes in the nucleus, the code for hemoglobin synthesis must have 

 been transferred from the DNA to the rihosome, perhaps by a mes- 

 senger RNA. Within the rihosome, protein synthesis is probably 

 organized as a cooperative enterprise in which ribonucleic acid and 

 protein both perform essential functions. Hemoglobin synthesis thus 

 sets forth in broad outline the essential features, as we presently 

 understand them, of the genetic control of specific protein synthesis. 



Much more interesting and significant from the viewpoint of devel- 

 opmental biology is the fact that the hemoglobin of the fetus and 

 newborn is different from that of the adult human. This fetal hemo- 

 globin, like adult hemoglobin, is composed of four polypeptide chains, 

 but the two /? chains of adult hemoglobin have been replaced by two 

 identical y chains, which differ significantly in amino acid composition 

 from the (5 chains ( Schroeder et al., 1961 ) . This difference in primary 

 protein structure implies that a different nonallelic gene is responsible 

 for the synthesis of the y polypeptides. Genetic evidence confirms this 

 implication. A fundamental principle of development is thus clearly 

 shown by this example, namely, that the synthesis of a specific protein 

 in the appropriately differentiated cells of a metazoan is dependent 

 upon the activation of the corresponding gene and not simply upon the 

 mere presence of the gene. During the first stages of embryonic develop- 

 ment, before the differentiation of erythrocytes, none of the genes for 

 hemoglobin synthesis appear to be active though they are surely 

 present in the cells of the embryo. Then, as erythrocytes begin to 

 develop, the a and y genes are activated and fetal hemoglobin is syn- 

 thesized. Later the y gene is suppressed and the ft gene activated, 

 although for a time both function together, producing mixtures of 

 adult and fetal hemoglobin. 



With this example of hemoglobin in mind, we may now state the 

 thesis of this lecture. During embryonic development the cells of an 

 organism undergo a progressive differentiation during which they 

 acquire a characteristic repertory of proteins, largely enzymatic, 

 which are the products of genie activity. The appearance of a new 

 protein in a cell is an indication that the gene for that protein has 

 been activated in that cell. By the same token the disappearance of a 

 protein indicates that the corresponding gene has been inhibited. 



