The adult alpha-globin locus of Old World monkeys: an abrupt breakdown of sequence similarity to human is defined by an Alu family repeat insertion site

Abstract

The haploid genomes of all known primates have two or more adult alpha-globin genes contained within tandemly arranged duplication units. Although the tandem duplication event generating these alpha-globin loci is believed to occur prior to the divergence of primates, a number of length polymorphisms exist within the loci among different primate species. In order to understand the molecular basis of these length polymorphisms, we have cloned and determined the nucleotide sequence of a major portion of the rhesus monkey adult alpha-globin locus. Sequence comparison to human suggests that the length difference between the adult alpha-globin loci of human and Old World monkey is the result of one or more DNA recombination processes, all of which appeared to be related to the transposition of Alu family repeats. First, the finding of a monomeric Alu family repeat at the junction between nonhomology block I and homology block Y of the alpha 2 gene-containing unit in rhesus macaque suggests that the dimeric Alu family repeat, Alu 3, at the orthologous position in human was generated by insertion of a monomeric Alu family repeat into the 3' end of another preexisting Alu family repeat. Second, two Alu family repeats, Alu 1 and Alu 2, exist in human at the 3' end of each of the two X homology blocks, respectively. However, this pair of paralogous Alu family repeats is absent at the corresponding positions in rhesus macaques. This raises interesting questions regarding the evolutionary origin of Alu 1 and Alu 2. Finally, DNA sequences immediately downstream from the insertion site of Alu 2 are completely different between human and rhesus macaque.(ABSTRACT TRUNCATED AT 250 WORDS)