446 



CHAPTER 49 



tron be identified by experimental means. 



Let us examine the basic premise involved, 

 which states that one genetic unit, or cistron, 

 has one primary function besides replication. 

 This was presented as a working hypothesis 

 in the hope that its acceptance would lead to 

 experiments which would result in a better 

 understanding of the functional unit of genetic 

 material. This hypothesis, however fruitful 

 may have been the consequence of its ac- 

 ceptance, has never been proved (refer to 

 p. 278). What basis have we for such a 

 conclusion? Suppose we start with a mor- 

 phological or biochemical pleiotropism whose 

 pedigree can be traced back to fewer and 

 fewer causes. If, after tracing the pedigree 

 back as far as our techniques permit, we find 

 there are still two or more apparently un- 

 related effects, the proponent in favor of the 

 one cistron-one function hypothesis can 

 always claim that had we searched longer 

 with better techniques, we would find this 

 pleiotropism has a single basis. Or, if we 

 are able to trace a group of pleiotropic ef- 

 fects back to a single origin, opponents of 

 this hypothesis can still state that had we 

 looked harder and better we would find still 

 other, not yet known, effects which would be 

 unrelated to the single factor which explains 

 all the presently known pleiotropic effects. 

 We must conclude, therefore, that we can- 

 not decide what a primary effect of a gene 

 is merely from the number of effects detected. 



However, we have used the idea, that if 

 we find a one-to-one correlation between 

 any effect and a gene change, the phenotypic 

 effect is directly, hence primarily, the result 

 of gene action. In this way, for instance, we 

 tested the idea that polypeptide sequence is 

 determined in a primary way by nucleotide 

 sequence. We found, in the case of hemo- 

 globin, that mutation was directly asso- 

 ciated with a change in its amino acid com- 

 position. Acceptance of the hypothesis one 

 polypeptide-one cistron, however, does not 

 mean that the reverse is true, namely, one 



cistron-one polypeptide, that is, that all cis- 

 trons have as their primary function the 

 specification of polypeptides. The reserva- 

 tion was made that cistrons also might act 

 in a primary way to specify other substances. 

 In this connection, it should be mentioned 

 that operator genes are recognized by having 

 a primary effect upon the functioning of other 

 genes, and that thus far such genes have not 

 been demonstrated to specify any chemical 

 product whatsoever. 



When we speak of a phenotypic result as 

 being affected by a gene in a primary way, 

 do we mean anything other than that there 

 is a one-to-one relationship between gene 

 and phenotype? Do we mean that the first 

 action of a gene is, at least in some cases, the 

 specification of amino acid sequence? No! 

 For we have evidence from hemoglobin and 

 other proteins that their synthesis takes place 

 in the cytoplasm, physically isolated from 

 conserved DNA. In these cases the amino 

 acid sequence is specified by messenger RNA 

 nucleotide sequence. In such cases, then, it 

 is clearly more correct to consider RNA 

 specification as being caused in a primary 

 way by genie action than it is to claim the 

 same for amino acid sequence. 



Let us discuss the matter of gene action 

 by starting not from a phenotypic result 

 and working back toward the gene, but 

 from the other direction, starting with the 

 gene. The genetic activity we know most 

 about directly is replication. In DNA 

 replication the single DNA strand is re- 

 markably passive, in that it is neither energy- 

 supplying, nor appreciably modified in its 

 own structure, nor irreversibly changed in 

 any directional manner, nor acting enzy- 

 matically. What then are the properties of 

 DNA which are responsible for its capacity 

 to serve as template? These properties must 

 include the physical configuration of linearly 

 arranged nucleotides as well as the specific 

 pattern of their electrical charges, both of 

 which seem to act more in a physical than in 



