Gene Action and Polypeptides 



419 



From which gene, a or y, did the gene 

 for (3 chains arise? Since the (3 A chain is 

 known to differ from both the a A and y F 

 chains by about 21 to 23 amino acids, we 

 are told nothing about which of the last two 

 was the ancestral type of the (3 chain. Al- 

 though just about as many mutants involv- 

 ing the a as the f3 chain have been discov- 

 ered, only those affecting the (3 chain occur 

 in the population with any appreciable fre- 

 quency. This finding, together with the 

 similarities between vertebrate a chains 

 mentioned earlier, suggests that in the te- 

 tramer changes in the « dimer produce a 

 greater selective disadvantage than those in 

 the (3 chain. Remember that a change in 

 gene « A modifies both fetal and adult he- 

 moglobin. It may also be that certain a 

 chain changes result in loss of ability to form 

 tetramers. The homotetramer of a, a A , 

 may not be possible, although (3 chains can 

 form f3 A and y chains can form y|\ We, 

 thus, conclude that the ancestral (3 gene was 



probably derived from one of the products 

 of a duplication of the y gene. 



As mentioned previously, the (3 A and 8 A2 

 chains differ in less than ten amino acids. 

 Presumably, the (3 gene was duplicated in 

 the genome, and one of the two resultant 

 genes mutated to become the 8 gene; that 

 the duplication is recent is suggested by the 

 small number of amino acid differences be- 

 tween the (3 A and 8 A * chains; by the appar- 

 ent persistence of linkage of the f3 A and 8 A - 

 genes; and by the restriction in the occur- 

 rence of A L .-like hemoglobin to the primates. 

 In summary, it is likely that by means of 

 gene duplication and intragenic mutations, 

 the ancestral gene, a, gave rise to the myo- 

 globin gene on one hand and the gene se- 

 quence, a -> y -» f3 — » 8, on the other. 

 Since polypeptides are apparently primary 

 products of gene action, the study of poly- 

 peptides should considerably advance our 

 understanding of the molecular basis of evo- 

 lution. 



SUMMARY AND CONCLUSIONS 



The biochemical activities necessary for the existence of protoplasm are controlled by 

 the nucleus, presumably by the genes it contains. These chemical reactions occur in 

 sequences that form many-branched, metabolic pathways leading to the chemical, phys- 

 ical, physiological, developmental, and morphological aspects of the phenotype. Be- 

 cause of this branching most, if not all. genes have pleiotropic effects. 



The phenotypic differences produced by different alleles can be traced back toward 

 the gene by a pedigree of causes. Such studies demonstrate that genes produce their 

 effects at the metabolic level. 



The study of inborn errors of metabolism in man demonstrates that by their influence 

 upon enzymes genes control various steps in biochemical sequences, and in these cases, 

 the effect on enzymes appears to be the primary and the only consequence of gene 

 action. 



In view of these experimental results, a one gene-one primary effect relationship is 

 hypothesized — that a gene produces only one primary effect and that any primary 

 effect is the result of the action of a single gene. The specific hypothesis, one enzyme- 

 one gene, proposed as a test of the general hypothesis, is supported by biochemical 

 and genetic studies of auxotrophy (for B^ tryptophan, adenine, and other nutrients) 

 in Neurospora. 



The biochemical genetics of tryptophan synthetase in E. coli and of hemoglobin 

 require that the hypothesis of "one enzyme-one gene" be generalized to "one polypep- 



