414 



CHAPTER 32 



TRY CLY LYS VAL 



Cl.Y ALA HIS ALA CLY 



CUI ALA LEU 



MET PHE LEU- 



THY CLY LYS VAL 



CUI ALA LEU 



LEU LEU VAL- 



VAL LYS LYS CLY HIS 



LYS PRO ASN CLY MET VAL ALA ASP PRO THR 



SER LEU ASP 



CLY PHE SER CLU PHE PHE ARC CLN 



VAL LYS LYS CLY HIS 



ALA SER CLY HIS 



SER LEU ASP 



1'Ht HIS PRO PHE TYR THR LYS 



LEU THR ASN ALA VAL 



PKE SER ASP CLY LEU 



MET PRO ASN ALA LEU SER ALA 



LEU LYS CLY THR PHE ALA THR 



VAL ASP PRO 



VAL ASP PRO 



■THE VAL LEU THR SER LYS TYR ARC 



ASP ALA LEI 

 140 



ALA HIS LYS TYR HIS 



figure 32-6. The amino acid sequences of the a and fj peptide chains 

 of Hh-A. The amino acids enclosed by solid lines are identical and 

 occupy corresponding positions along the peptide chains. The amino 

 acids are numerated sequentially from the N -terminus. {Reproduced 

 by permission of Dr. Vernon M. Ingram.) 



hemoglobin A, with the exception that the 

 sixth amino acid in peptide 4 has valine sub- 

 stituted for glutamic acid (the particular 

 amino acid italicized in the sequence given 

 earlier in the text) (see also Figure 32-5). 

 The heterozygote produces both this type of 

 abnormal hemoglobin, called hemoglobin S 

 (Hb-S) and hemoglobin A. Other studies 

 of the gene for sickling (see Chapter 6 and 

 p. 209) show that all of its manifold pheno- 

 typic effects are traceable through a pedi- 

 gree of causes to this single amino acid sub- 

 stitution in the /i A chain. 



Another mutant, known to be located on 

 the same chromosome as the gene for sick- 

 ling, produces hemoglobin C which differs 

 from hemoglobin A by replacing the same 

 glutamic acid in the fi A chain, this time with 

 lysine. Still another genetic change pro- 

 duces another hemoglobin, hemoglobin G. 



The amino acids in all the trypsin-produced 

 peptides are the same as in hemoglobin A, 

 except that the seventh one from the N-ter- 

 minus in peptide 4 is glycine instead of 

 glutamic acid. In this case, then, the amino 

 acid sequence in peptide 4 is: Val-His-Leu- 

 Thr-Pro-Glu-G/y-Lys. . . . Here, an amino 

 acid in a different position — position 7 — in 

 the B A chain is changed. In hemoglobin E 

 a glutamic acid — normally found in position 

 26 on the fi x chain (see Figure 32-6) — is 

 replaced by lysine; this probably is the only 

 change in the whole molecule. 



The preceding is evidence that different 

 mutants cause single amino acids located in 

 different positions in the fl x chain to be re- 

 placed by other single amino acids. Al- 

 though the precise genetic basis for the dif- 

 ferent mutants is unknown, the available 

 evidence strongly indicates that all these 



