464 CORRADO BACLIONI 



1961). The t'uiu'tion of such a i-cgiilaloi- ii,vnc is to turn off the y chain 

 production and to turn on the (3 and 8 chain production. The fact that 

 indivi(hials heterozytj;ous for the hijih F gene and for a f3^ or a /3*' gene 

 foi-in Ill)-S or llh-C in noiinal amount seems to indicate that tlie regula- 

 tor gene exerts its control only on the structural genes in cis, located on 

 the same chromosome (Neel, 1961). The suppression of S chains produc- 

 tion in the child liomozygous for the high F gene (Wheeler and Krevans, 

 1961) is in agreement with the idea that the regulator gene extends its 

 control over the [3 and S structural genes, which are known to be closely 

 linked (Ceppellini, 1959b). 



The mode of action of the high F gene is analogous in form with 

 that of the operator gene of Jacob and Monod (1961). The operator 

 gene has been defined by Jacob and Monod (1961) as a genetic element 

 which controls the expression of several adjacent structural genes; the 

 operator as defined in the Lac system of Jacob and Monod is the site of 

 action of repressors produced by regulator genes. The interaction of 

 regulators, operators, and structural genes results in the repressive 

 genetic regulation of protein synthesis. 



In Fig. 14 the high F mutation has been indicated as o~ and the normal 

 allele as o^, by analogy with the nomenclature of Jacob and Monod 

 (1961). The close linkage of the postulated o gene with the jS and 8 

 genes is in agreement with the structure of the coordinated unit of genetic 

 expression defined by Jacob and Monod (1961) as operon. It must be 

 realized that the existence of an operator among the hemoglobin genes is 

 not substantiated by genetic evidence minimally comparable to that 

 obtained by the fine genetic analysis of the Lac region of E. coli. It is 

 extremely useful, however, to borrow Jacob and Monod's model of the 

 operon to explain tentatively the chemical findings for the high F condi- 

 tion. This model provides the investigator with a challenging hypothesis, 

 and may be apt to stimulate further experimentation and criticism. 



In the operator gene model it is hard to understand the relationships 

 between concomitant events: the suppression of /? (and 8) chain produc- 

 tion and the persistent synthesis of y chains. In order to explain these 

 apparently linked events, one has to assume that the /3-8 operator, which 

 is controlled via repression by a regulator gene, in its turn controls the 

 y operator. In this way the synthesis of y chains may be shut off at the 

 same time that the synthesis of /? and 8 chains is activated. However, 

 only one y gene, presumably the one in cis if y is linked to /? and 8, 

 should fall under this control, since the normal operator in the hetero- 

 zygotes does not suppress y chain production. Nothing is known about 

 the position of tlie y locus, since y alleles have not been found. The 

 operator gene hypothesis is still highly speculative in the case of the 



