RODENT HEMOGLOBIN STRUCTURE: A COMPARISON OF SEVERAL SPECIES OF MICE *

Recent studies of the structure and genetics of hemoglobin have shown several instances of clusters of genes producing sets of closely related globin polypeptide chains. The first such cluster to be demonstrated was the pair of genes coding for the @ and S chains of humans.’ Closely linked pairs of achain genes have been found in some individuals in Hungary,2 although in Melanesia there are individuals with only one a-chain IOCUS.~ There may be as many as four ychain loci clustered together in humans.4 I will call a closely linked pair, such as the genes coding for human /3 and S chains, a “doublet,” and a single gene a “singlet;” the terminology is based on that of Spofford.s Mice provided one of the first examples of a globin chain doublet in nonhumans. In 1962, Hutton and colleaguese.7 showed that some inbred strains of mice have an adult @-chain doublet producing two @ chains in unequal amounts, which subsequently was called Hbbd; other strains have an adult @-chain singlet, Hbb8. Morton8 discovered a third allele at the @-chain locus of mice, HbbP, with the p hemolysate bearing some resemblance to the d hemolysate. The conclusions of Hutton and colleagues remained in some dispute until recently, because there were no actual sequence data confirming that the d hemolysate contains two structurally different @ chains. In 1972, I reported that the hypothesis of Hutton and colleagues was correct; I isolated two hemoglobins from the d hemolysate and showed that they possess structurally different @ chains, p m i n (produced as about 20% of the total) and $“I (accounting for the remaining @-chain production) .g I also confirmed that HbbP is a variant of the Hbbd allele, since it produces a variant minor B chain, @pmin. Rifkin 10, l1 presented tryptic peptide composition data on and p m a j , and Popp has sequenced most of p l2 and /3dmsJ.l3 A summary of my data and those of Rifkin and Popp, showing the differences that are known among the /3 chains of laboratory strains of mice, is shown in FIGURE 1. Mice have also been shown to have a-chain doublets. Rifkin and colleagues1° showed in 1966 that one inbred strain of mice has two a chains, which differ from each other in at least one position. Another inbred strain that they examined has only one a chain. Von Ehrenstein l4 had earlier found that the rabbits he examined have two a chains; he suggested that perhaps only a single gene was responsible for producing both chains, by means of “ambiguous translation.” Rifkin and colleagues suggested that translational ambiguity