56 BIOCHEMICAL SYSTEMATICS 



Actually, Anfinsen's question may be modified to apply to 

 enzymes, which are generally assumed to be direct or indirect template 

 products of genes, and further subdivided: 



(1) Do widely separated organisms, which possess the ability 

 to synthesize a certain substance, employ the same 

 sequential order and precursor series, implying enzymatic 

 homology, or do they travel different roads to the same 

 destination? 



(2) If two biochemical sequences are identical stepwise, to 

 what extent are the enzymes involved homologous and 

 thus identical or nearly so? The minor differences in, say, 

 ribonuclease, of different organisms would not seem to 

 suggest non-homology. 



With respect to the second question, if only a small active 

 site has critical spatial arrangement, then independent evolution of an 

 enzyme might be expected to yield chemically different enzymes— un- 

 less new enzymes evolve by minor variations in a member of a pair of 

 repeats. This last idea is expressed in detail by Demerec and Hartman 

 (1956) following studies of non-random distribution of genes in- 

 volved in histidine and tryptophan synthesis in Salmonella. Non- 

 random gene distribution appears to be characteristic of amino acid 

 synthesis in Salmonella. More recently it has been reported that 

 4-threonine and 5-isoleucine-valine loci are clustered in an order 

 corresponding to the sequence of biochemical reactions they control 

 (Glanville and Demerec, 1960). Nonetheless the examples of non- 

 random gene distribution of which we are aware at present are found 

 in only a few organisms and may not represent a widespread phenom- 

 enon. In Horowitz' words (1950): 



Biochemical mutants of Neurospora should provide excellent material 

 for study of the possibility of non-random gene distribution. At present, 

 all that can be said is that if such a distribution exists, it does not leap 

 to the eye. 



The situation, at present, in Neurospora is essentially unchanged al- 

 though Wagner et al. (1958) have described a system involving valine 

 and isoleucine synthesis wherein the gene sequence seems to be cor- 

 related with a sequence of metabolic steps. 



In connection with the question of comparative enzyme 

 chemistry, the following excerpt from a discussion at a recent sym- 

 posium (Haslewood, 1959) illustrates the trend of thought among bio- 

 chemists at present. 



