Tlie Protein Text 73 



II. GENETIC EFFECTS ON PROTEINS 



There is an increasing body of evidence indicating that tiie details of protein 

 structure are genetically determined. A study of the effect of mutations on 

 proteins should therefore tell us something both about the nature of mutations 

 and the protein forming mechanism. Known cases of genetic effects on proteins 

 are listed below. 



1. In man hemoglobin occurs in several electrophoretically distinguishable 

 forms, the presence of each being apparently controlled by alleles of a single 

 gene (26). Hemoglobin C differs significantly in amino acid composition 

 from hemoglobin A (27). Hemoglobin A and S have been degraded in a 

 controlled fashion with trypsin and the resulting peptides separated. The 

 difference between these hemoglobins is apparently confined to a short section 

 of the molecule (28). 



2. Two electrophoretically different hemoglobins occur in sheep. Their 

 presence is determined by alleles of a single gene (29). 



3. Two forms of lactoglobulin occur in cow's milk, and like the hemo- 

 globins are determined by different alleles of one gene. Crystallographic 

 investigations indicate unit cells of the same size, but there are very slight 

 differences in the diffraction pattern, which the investigators attribute, possibly, 

 to the substitution of a few amino acid residues by others (30). 



4. Mutants of Neurospora and Escherichia co/i produce abnormally heat- 

 labile forms of tyrosinase (31) and a panthothenic acid synthesizing enzyme (32), 

 respectively. It is clear that a change in the proteins has occurred, but unfor- 

 tunately there is no further information on its physico-chemical nature. 



The genetic evidence indicates that there is no interaction between alleles 

 controlling the synthesis of different variants of one protein. If both alleles 

 are present, both types of protein are formed. A possible exception should 

 be noted. The N-terminal groups of wheat gliadin are reported to be phe, 

 of rye gliadin phe and glx, but unexpectedly the ghadin of wheat x rye hybrids 

 was found to have no amino or carboxyl terminal ends, indicating, possibly, 

 a cyclic protein (33). This case obviously needs further study*. 



The evidence cited above shov/s that the properties of proteins are gene- 

 determined, but it does not indicate clearly what these properties are. More 

 detailed information is available on this point from a comparison of homo- 

 logous proteins of related species, if it is assumed, as is usually done, that 

 species differences are the result of gene mutations. 



Available evidence on amino acid sequence of homologous proteins is 



* There is considerable confusion as to the N-terminal residues of wheat gliadin. Fraenkel- 

 CoNRAT (51) misquotes Deich and Soreni (33) as stating that the N-terminal residues are 

 phenylalanine and histidine, apparently because of a misunderstanding in Chemical Abstracts 

 (138). KoROS, whose paper I was able to consult only in abstract (139), reports histidine as 

 N-terminal. Ramachandran and McConnell (140), working with wheat gliadin but failing to 

 specify the species, also find histidine. Deutsch (the same as Deich quoted above, the differ- 

 ence in spelling being due to transliteration from the Cyrillic) reports that gliadin from Triticiim 

 durum and Triticum milgare has N-terminal phenylalanine (141). This is misquoted as tyrosine, 

 and tyrosine and glutamic acid, respectively, by Ramachandran and McConnell (140). 

 The original paper of Deutsch (141) was also unavailable to me. 



