CONCERTED EVOLUTION LED TO HIGH EXPRESSION OF A PROSIMIAN PRIMATE DELTA-GLOBIN GENE LOCUS

The delta-globin gene in simian primates is either weakly expressed (in hominoids and New World monkeys) or silent (in Old World monkeys). In prosimian primates, however, an unequal homologous crossover between the psi-eta and delta-loci of lemurs produced a hybrid psi-eta-delta-pseudogene locus, whereas in tarsier the delta-locus encodes a beta-type chain found in 18% of adult tarsier hemoglobin molecules. In the present study, the nucleotide and amino acid sequences of the galago-delta and beta-globin genes and their encoded peptides were determined, and evidence is provided showing that the galago-delta-locus encodes a beta-type chain (beta-2) found in 40% of the galago fetal and postnatal hemoglobin molecules, whereas the beta-locus encodes the remaining 60% of the beta-type chain (beta-1). Galago beta-1 and beta-2 chains differ from each other by only one amino acid residue. The homology between the galago delta and beta-loci extends from 800 base pairs 5' of the proximal CCAAT element to near the end of exon 3 as a result of a recombination event in which beta-sequence replaced delta-sequence. After this initial recombination event, concerted evolution between the loci continued over their conserved coding, intron 1, and promoter regions but failed to occur between the two loci in their intron 2 and distal 5'-flanking sequences where the two loci have now diverged by 20%. Calculations based on this divergence value and on a rate of noncoding sequence evolution of 4.2 x 10(-9) to 5.5 x 10(-9) substitutions/site/year for the lorisform lineage to galago yielded a date of 18-24 million years ago for the initial recombination event. The fact that the promoter sequences of the galago delta-locus are the same as that of the galago beta-locus may account for the high level of expression of the galago delta-gene.