The relationship between the common mutations of the alpha gene cluster and its evolutionary history

The alpha globin gene cluster is far from static. It shows remarkable diversity within and among populations, both in gene number and the pattern of polymorphisms involving the HVRs. The deletions which have given rise to alpha o thalassemia appear to have resulted from rare genetic events and the affected chromosomes have been distributed among localized populations by selection. On the other hand, the deletions which have given rise to at least one of the alpha+ thalassemias seem to have occurred on multiple occasions in different populations. The genesis of this condition, the commonest single gene disorder, may reflect the concerted evolution of the alpha globin genes, and the alpha+ thalassemias may have arisen as a by-product of this evolutionary process. The existence of such a polymorphic gene family and the fact that its mutations are the commonest single gene disorders in man, provide us with a remarkable, natural model for studying population genetics at the molecular level. Further analysis of this cluster, and of the beta globin genes, may provide valuable information about the timing of racial diversions, population movements, and the molecular events which have helped to maintain such high gene frequencies for some of the mutations of these loci.