448 CORRADO BAGLIONI 



hcmoglohin. whit'h is excliulcd from the fiiiG;c'r|)i'intinfz; analysis. The 

 Hb-Lcporo aljuonnality thus seems to involve a mutation of the /? locus, 

 resulting in comj)lete suppression of /3 chain synthesis and a simul- 

 taneous mutation of the 8 locus, resulting in the synthesis of an electro- 

 ]>horetically abnormal heiuoglobin. Ilb-Lepore. It is rather hard to 

 understand why these independent mutations in the two linked genes fS 

 and S should always be observed in c()ui)lii^g. The S"- mutation has, for 

 instance, been observed either in couj^ling oi' in repulsion with a Z?"^'' 

 gene (Ceppellini, 1959a; Horton et al., 1961). 



It seems likely that a common genetic event is responsible foi- both 

 the absence of fS chains and the alteration of the "8" chains; the only 

 genetic event involving two neighboring genes at the same time is an 

 overlapping deletion of genetic material, resulting either from mutation 

 or from unequal crossing-over. 



It has recently been suggested by Smithies et al. (1961) that a 

 mechanism of unequal crossing-over between two haptoglobin genes 

 could be responsible for the duplication in length of one peptide chain 

 of the human haptoglobins. A similar mechanism can be advocated to 

 explain the puzzling genetic and chemical findings on Hb-Lepore: in this 

 case loss of genetic material by unequal crossing-over, may result in the 

 formation of a hybrid ;S-8 gene, having part of the genetic material of 

 both the j3 and the 8 genes. 



The chemical findings on Hb-Lepore so far do not contradict this 

 theory; only that part of the "8" chain of Hb-Lepore, going from the 

 N-terminal end of the peptide chain to approximately halfway along 

 the chain, has been shown to give a fingerprint similar to the 8 chain 

 of Hb-Ao, while no information exists about the C-terminal portion of 

 the "8" chain of Hb-Lepore. The possibility exists that the C-terminal 

 part of the "8" chain of Hb-Lepore is identical to the p chain of Hb-A.^ 



It is known that unequal crossing-over frequently involves chromo- 

 somal duplications like the bar duplication of Drosophila inelonngaster 

 (Bridges, 1936) ; double-bar and normal flies appear with relatively high 

 frequency as a result of unequal crossing-over in liomozygous bar 

 females. 



It has been suggested that the 8 gene results from a duplication of 

 the (3 gene, followed by independent evolution (Ingram, 1961a). Profound 

 homologies exist between the (3 gene and the 8 gene, since the primary 



'Recent exi)eriment.s (Baglioni, unpubli.shed) have shown that the C-terminal 

 portion of the 5 chain of Hb-Lepore is identical to the C-terminal portion of the 

 P chain of Hb-A. Two amino acid replacements have been located by A. O. W. 

 Stretton (unpubHshed) in the C-terminal portion of the S chain of Hb-.\,. These 

 replacements are not pre.sent in the 0-8 chain of the Hb-Lepore. 



