Assignment of orthologous relationships among mammalian α-globin genes by examining flanking regions reveals a rapid rate of evolution

In order to study the relationships among mammalian α-globin genes, we have determined the sequence of the 3' flanking region of the human α1 globin gene and have made pairwise comparisons between sequenced α-globin genes. The flanking regions were examined in detail because sequence matches in these regions could be interpreted with the least complication from the gene duplications and conversions that have occurred frequently in mammalian α-like globin gene clusters. We found good matches between the flanking regions of human α1 and rabbit α1, human ψα1 and goat (I)α, human α2 and goat (II)α, and horse α1 and goat (II)α. These matches were used to align the α-globin genes in gene clusters from different mammals. This alignment shows that genes at equivalent positions in the gene clusters of different mammals can be functional or nonfunctional, depending on whether they corrected against a functional α-globin gene in recent evolutionary history. The number of α-globin genes (including pseudogenes) appears to differ among species, although highly divergent pseudogenes may not have been detected in all species examined. Although matching sequences could be found in interspecies comparisons of the flanking regions of α-globin genes, these matches are not as extensive as those found in the flanking regions of mammalian β-like globin genes. This observation suggests that the noncoding sequences in the mammalian α-globin gene clusters are evolving at a faster rate than those in the β-like globin gene clusters. The proposed faster rate of evolution fits with the poor conservation of the genetic linkage map around α-globin gene clusters when compared to that of the β-like globin gene clusters. Analysis of the 3' flanking regions of α-globin genes has revealed a conserved sequence ~100-150 bp 3' to the polyadenylation site; this sequence may be involved in the expression or regulation of α-globin genes.