IX. GENETICS AND HUMAN HEMOGLOBIN CHEMISTRY 419 



Ingram and Stretton (1959a) investigated the chemical nature of 

 Hb-Ao by fingerprinting and determined the sequence of a few peptides 

 of this hemoglobin. Few differences were observed in the fingerprint of 

 Hb-A;., when comjiared to the fingerprint of Hb-A. The differences were 

 localized to /? chain peptides. Muller and Jonxis (1960) and Ingram and 

 Stretton (1961) separated the peptide chains of Hb-A^ and fingerprinted 

 the isolated chains. Hb-A:.. appears to have a pair of chains identical to 

 tiie a chains of Hb-A; peptide chains different from the /? chains of 

 Hb-A are associated with the a chains in Hb-Ao ; these peptide chains 

 have been designated 8 chains. Ingram and Stretton (1961, 1962) isolated 

 several of the peptides of the S chain of Hb-Ao and determined their 

 amino acid composition and some of their amino acid sequences. The 

 S chains of Hb-Ao have been found to be surprisingly similar to the 

 (3 chains of Hb-A. Only 4 residues out of 146 have been shown to be 

 definitely different between these two chains (Ingram and Stretton, 

 1961) and there is preliminary evidence for at least 4 further changes 

 (A. 0. W. Stretton, personal communication). 



D. CONSIDER.\TIONS ON THE AMINO ACID SEQUENCE OF THE 

 HUMAN HEMOGLOBIN CHAINS 



In Figs. 3 and 4 the amino acid sequences of the a, (3, and y chains 

 are shown together in order to point out the similarities existing 

 between these peptide chains. In the case of the /? and y chains the 

 similarities are striking. If one calculates the relative number of amino 

 acids in corresponding positions along these peptide chains which are 

 found to be identical, one can observe 42% correspondence between the 

 a and the /? chains, 39% correspondence between the a and the y chains, 

 and 71% correspondence between the (3 and the y chains. The y chain 

 is certainly more similar to the /? chain than to the a chain; most of 

 the correspondences between a and y chains are present also in the ft 

 chain. The analysis of the correspondence can be extended to the S 

 chain, for which no ordering of the peptides has been provided, if one 

 assumes that peptides with identical or very similar sequence or com- 

 position occupy a similar position along the f3 and 8 peptide chains. An 

 upper limit for the extent of correspondence between the ^ and the S 

 chains can be established in this way at 94%. 



In 1957, when the stiTicture of the human hemoglobins and the 

 sequence of the hemoglobin chains were not yet elucidated, Itano con- 

 sidered the possibility that the genes for myoglobin — Hb-A, Hb-F, and 

 Hb-Aj — were derived from a primitive gene through a process of gene 

 duplication and independent evolution of the dujilicated genes. This 

 hypothesis has been examined in greater detail by Ingram (1961a) on 



