440 



CORRADO BAG LION I 



Fic. <>. ^e'liciuatic oxplanatiou of the presence of four hemoglobins in doubly 

 heteroz3'gous individuals (Atwater et al., 1960a; Baglioni and Ingram, 1961). The loci 

 controlling the synthesis of the a and /? peptide chains are represented on the left. 

 The arrows show the different dimers synthesized under the control of the a and p 

 alleles and the random combination of these dimers in the last stage of the 

 assemljly of the hemoglobin molecule. The letters A, G, C, and X indicate the four 

 hemoglobin types synthesized. Hb-A results from the combination of a-/ dimers 

 with ^jA dimers, Hb-G from the combination of a.p dimers with P-,^ dimers, Hb-C 

 from the combination of a.,^ with p.,^ dimers, and Hb-X from the combination of 

 a2^' with jSj^ dimers. 



has yet been reported to be produced by experiments of dissociation and 

 recombination; however, the hemoglobin molecule is not dissociated to 

 single chains in these experiments. (Hasserodt and Vinograd, 1959). 



D. DISSOCIATION AND RECOMBINATION OF HEMOGLOBIN 



Field and O'Brien (1955) reported that hemoglobin dissociates 

 reversibly at acid and alkaline pH's into subunits of molecular weight 

 approximately half that of undissociated hemoglobin. Itano and Singer 

 (1958) applied the acid dissociation method to the study of the dissocia- 

 tion and recombination of mixtures of hemoglobins A, S, and C. Singer 

 and Itano (1959) and Vinograd et al. (1959) observed transfer of C^''- 

 labeled subunits from Hb-A to Hb-C or Hb-S upon dissociation and 

 recombination. When equivalent amounts of Hb-A^'^ and Hb-C were 

 recombined, one quarter of the radioactivity was found to be transferred 

 to Hb-C. By these experiments Itano and his collaborators and Vinograd 

 et al. (1959) have been able to show that different hemoglobins exchange 

 subunits by a specific mechanism of dissociation and recombination, 

 which results in the formation of hyl)rid molecules. However, formation 

 of hybrid molecules containing two different a or ^ chains does not occur. 

 Recombination of hemoglobins altered in different chains provides a 



