Gene Action and Polypeptides 



417 



his children. The father's genotype would 



a A # S 8 A - 

 be, therefore, = As expected, he 



a A ft A 8"°- 

 actually made four kinds of hemoglobin — 

 Hb-A, Hb-S, Hb-A,, Hb-B,. Finally, we 

 find that, as expected, heterozygotes for 

 Hb-I make not only Hb-A and Hb-1 but 

 also make Hb-A L . and a defective Hb-A 2 

 composed of al6 A -. Dimers of the a chain 

 apparently combine in a random way with 

 dimers of the ft and 8 chains. 



Hemoglobin F. The hemoglobin of the 

 fetus hemoglobin F has two a chains like 

 those in adult hemoglobin A. Accordingly, 

 persons with mutant a A genes make Hb-F 

 whose a chains have the same abnormality 

 as has Hb-A. The other two chains in 

 Hb-F are different from the ft, 8, and a 

 chains and are called y chains; thus, normal 

 hemoglobin F is a%y\. The arrnno ac id 

 sequence in the y F chain of Hb-F is given 

 in Figure 32-8. Homozygotes for the sick- 



ling gene can make hemoglobin F which is 

 apparently normal, a^yfj so that a change 

 in the ft chains has no effect on the y chains. 

 Some known abnormal types of Hb-F are 

 believed to be altered in the y chain. It is 

 very likely, therefore, that a separate gene, 

 y p , specifies y F chains and has allelic alter- 

 natives. Hb-A appears in the fetus as early 

 as the 20th week and gradually replaces 

 Hb-F; even at parturition, however, there 

 is still some Hb-F in the blood. The change 

 from Hb-F to Hb-A means that during de- 

 velopment the y F gene has its action turned 

 off, so to speak, and gene ft A has its action 

 turned on. 



The preceding evidence indicates that 

 four genes are involved in the manufacture 

 of fetal and adult hemoglobin, namely — a, 

 ft, 8, and y. All results support the view 

 that each kind of polypeptide chain in he- 

 moglobin is completely specified by a unique 

 gene. Because heterozygotes for mutants 



SER ALA VAL 



ALA THR ILBJ 



LEU TRY GLY LYS VAL ASN VAL 



LEU TRY CLY LYS VAL ASN VAL 



ASP CLU VAL 



GLU ASP ALA 



GLY CLY CLU 



GLY GLY GLU 



LEU CLY A*G LEU LEU VAL VAL TYR PRO 



LEU GLY ARG LEU LEU VAL VAL TYR PRO 



• GLY LEU SER THR 



• • SER PHE ALA CLY 



LEU VAL LYS LYS GLY HIS ALA LYS VAL LYS PRO ASN GLY MET 



LEU VAL LYS LYS GLY HIS ALA LYS VAL LYS PRO ASM GLY MET 



SER ALA SER 



ASP PRO THR 



GLY PHE SER 



PHE PHE ARG CLN THR TRY 



PHE PHE ARG GLN THR TRY 



GLY LEU ALA 



ALA HEU LYS 



HIS LEU ASP ASP LEU LYS GLY THR PHE ALA 



HIS LEU ASP ASP LEU LYS CLY THR PHE ALA 



LEU HIS CYS 



LEU HIS CYS 



LYS LEU HIS VAL ASP PRO 



LYS LEU HIS VAL ASP PRO 



LEU LEU GLY ASN ' 



LEU LEU GLY ASN ■ 



LYS HIS ALA LEU ALA ASP ALA VAL CLY ALA VAL VAL LYS GLN TYR ALA ALA CLN VAL PRO PRO THR PHE GLU LYS GLY PHE HIS HIS ALA LEU VAL CYS VAL LEU VAL 



ALA VAL CLY 



ALA GLN VAL 



PRO THR PHE GLU LYS GLY PHE HIS 



ALA LEU VAL 



VAL LEU VAL •" 



figure 32-8. The amino acid sequence of the ft peptide chain of Hb-A and of 

 the y peptide chain of Hb-F. The amino acids enclosed by solid lines are identi- 

 cal and occupy corresponding positions along the peptide chains. The amino 

 acids are numerated sequentially from the N-terminus. (Reproduced by permis- 

 sion of Dr. Vernon M. Ingram.) 



