A study on the β-globin gene cluster in man and the primates
Human haemoglobins are coded for by two unlinked clusters of alpha and beta-globin genes. The human beta-globin cluster appears to have evolved by a series of tandem gene duplications and contains considerable stretches of intergenic DNA possibly involved in the developmental control of globin gene expression. In order to understand the evolution of this cluster, the arrangement of primate beta-related globin genes has been determined by restriction endonuclease mapping of genomic DNA from species ranging from prosimians to the great apes and these compared to the published genomic map of the human beta-globin gene cluster. The arrangement of the entire epsilonupsilonupsilonbeta beta-globin gene cluster in the gorilla, chimpanzee and yellow baboon is indistinguishable from that of man. Restriction site differences between these species are consistent with a surprisingly low overall rate of intergenic DNA sequences divergence of approximately 1x10-9 nucleotide substitutions per nucleotide site per year as compared with the currently accepted silent site rate of 5x10-9 nucleotide substitutions per nucleotide site per year. The owl monkey, a New world species, has a single upsilon-globin gene suggesting that the upsilon-globin gene duplication in man is ancient and occurred 20 to 40 million years ago---a surprising contrast to the very high degree of sequence homology existing between these two genes. The owl monkey appears to possess duplicated beta-globin genes suggesting that the deltabeta gene duplication is between 40 and 70 million years old. The beta-globin gene cluster in the brown lemur, a prosimian, is remarkably short (about 17,000 base-pairs) and contains single epsilon-, upsilon- and beta-globin genes. The upsilon- and beta-globin genes in this species are separated by a mosaic gene ([psi]beta') containing the 3' end of a beta-globin gene preceded by sequences related to the 5' end of the epsilon-globin gene as determined by hybridisation studies. The brown lemur beta-globin gene cluster has been cloned into a bacteriophage lambda vector as a set of overlapping DNA fragments covering the entire region and the 'psibeta' gene sub-cloned into a plasmid vector. Initial sequencing the 3' end of this gene has further indicated its beta-like nature.