Biochemical Genetics (II) 



289 



can be written a}^^. Hemoglobin H is pro- 

 duced by persons homozygous for the recon 

 for thalassemia (see p. 36) ; this type of hemo- 

 globin has four (3 chains of A type (instead of 

 two being a chains), so that it can be written 

 j8f . Such homozygous persons also produce 

 some hemoglobin A. It is also known that 

 fetal hemoglobin, hemoglobin F, has two a 

 chains like those in adult hemoglobin A; the 

 other two chains are different from ^ and 

 probably from a also, and are called y chains, 

 so that hemoglobin F is a^J^- Finally, it is 

 known that homozygotes for the sickling 

 recon can make hemoglobin F which is ap- 

 parently normal, a^y^, so that a change in 

 the (3 chains has no effect on the y chains. 



The results with the recon for sickling prove 

 that the synthesis of the nonenzymatic protein 

 globin is cistron-directed in a primary way. 

 What we would hke to decide is whether one 

 or more cistrons are involved. There are 

 several hnes of evidence which point to an 

 independent specification of a and (3 chains: 



1. Mutations that change the specifications 

 of the (3 chain (producing hemoglobins 

 S, C, E, G) produce no change in the a 

 chain. 



2. Mutations that change the a chain (pro- 

 ducing hemoglobins I, Hopkins-2) pro- 

 duce no change in the (3 chain. 



Further evidence consistent with the independ- 

 ent specification of a and (3 chains comes 

 from the study of individuals who possess 

 both Hopkins-2 and S hemoglobins. Such 

 individuals are known who have had one par- 

 ent like themselves and the other of normal 

 blood type (hemoglobin A). However, these 

 individuals also have siblings who have 

 Hopkins-2 but not S hemoglobin, and those 

 who have the reverse. Accordingly, these 

 Hopkins-2 + S persons cannot be mono- 

 hybrid but must be dihybrid, for the abnormal 

 hemoglobins occur both separately and to- 

 gether in different siblings. Moreover, the 

 number of sibHngs who must be recombinant 



is so large as to preclude the two mutant 

 recons being linked very close together. We 

 may write the genotype of these dihybrids as 

 f^no-2 ,„A fjs f^\ Since the two recons are not 

 very close together, they may be in different 

 cistrons. 



It has been shown that the two a and the 

 two (3 chains in a given globin molecule are 

 identical, even in heterozygotes. If the 

 Hopkins-2 + S individuals are dihybrid for 

 recons in different cistrons, it would seem 

 reasonable that the two a chains specified by 

 ,„Ho-2 (i^j^^t ig^ a""""), or by m^'ia^), would 

 be produced independently of the two ^ 

 chains specified by n^([3'^), or by rt"^((S^). If 

 so, then either product of the two different 



FIGURE 32-4. Normal hemoglobin and some ab- 

 normal types due to mutation. 



TYPE 

 Hgb A 



Hgb F 



Hgb S 

 Hgb C 

 Hgb G 

 Hgb E 

 Hgb I 



CHAINS 



A F 





^t 3^ 



A E 



2 ^2 



Ho-2 A 



SPECIFIC NAME 

 Aduir 



Normal 



Fetal 



Sickle cell 



Hgb Ho-2 oc 2 3 ^ 



Hgb H 



Hopkins No. 2 

 Thalassemia 



