Gene Duplication and Haemoglobin Polymorphism

Abstract

The introduction of electrophoretic techniques in the early 1950s soon led to the discovery that the haemoglobins of many animal species are polymorphic. In man the crucial discovery of haemoglobin S in the red cells of persons with sickle-cell anaemia was a striking illustration of the concept of disease at the molecular level, and it subsequently stimulated a great deal of research into the genetic aspects of the control of protein synthesis. Early ideas about the genetics of human haemoglobin were developed largely through family studies of individuals with various abnormal haemoglobins; particularly noteworthy were the findings of Smith & Torbert (1958) who established the existence of individual α-and β-chain genes, most probably on separate chromosomes. Haemoglobin variants proved to be the products of alleles of either α- or β-chain genes, and Hbs F and A₂ were shown to be due to the existence of separate γ- and δ-chain genes. The determination of the amino acid sequences established considerable homologies between the α, β, γ and δ-chains and it was suggested that these could be most simply accounted for by assuming that the genes which determine them were originally derived from a common ancestral gene. Successive duplications followed by separate evolution of the resulting genes by point mutations would then give rise to the different but related genes that exist today (Ingram 1961). The very close homology of the β- and δ-chains and the fact that the two genes lie close together on the same chromosome was taken as an indication that they have existed as separate entities only recently in evolutionary history.