Recombination and balanced chromosome polymorphism suggested by DNA sequences 5' to the human delta-globin gene

Two types of chromosome (R and T) were found by cloning from six human individuals the 3.1-kilobase-pair EcoRI fragment that contains the bipolar Alu family repeat 5' to the delta-globin gene. Two type T fragments were identical in nucleotide sequence. Two type R fragments were identical except for one base. Both types are found in whites, blacks, and orientals. The differences between R and T sequences (16 base substitutions and two deletions) were mostly in the 5' domain of the fragment (0.91% difference in 1.7 kilobases), which contains the bipolar Alu repeat, whereas the 3' domain of the fragment was more conserved (0.14% difference in 1.4 kilobases). To help understand the history of this human polymorphism, the equivalent fragment from a chimpanzee was cloned and its sequence was determined. The chimpanzee sequence differed from both human sequences at 39 positions distributed almost uniformly along the whole 3.1-kilobase-pair fragment. Assuming that humans and chimpanzees diverged 4 to 5 million years ago, the data indicate that the divergence of the two types of human chromosome started about 3 million years ago but about 0.4 million years ago an interchromosomal recombination rendered the two types of human chromosome alike in their 3' domains. The two chromosomes have since remained discrete and have persisted in several populations. These observations suggest that factors are operating to maintain a balanced chromosomal polymorphism in this region 5' to the human delta-globin gene.