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

In order to study the relationships among mammalian alpha-globin genes, wehave determined the sequence of the 3' flanking region of the human alpha 1globin gene and have made pairwise comparisons between sequencedalpha-globin genes. The flanking regions were examined in detail becausesequence matches in these regions could be interpreted with the leastcomplication from the gene duplications and conversions that have occurredfrequently in mammalian alpha-like globin gene clusters. We found goodmatches between the flanking regions of human alpha 1 and rabbit alpha 1,human psi alpha 1 and goat I alpha, human alpha 2 and goat II alpha, andhorse alpha 1 and goat II alpha. These matches were used to align thealpha-globin genes in gene clusters from different mammals. This alignmentshows that genes at equivalent positions in the gene clusters of differentmammals can be functional or nonfunctional, depending on whether theycorrected against a functional alpha-globin gene in recent evolutionaryhistory. The number of alpha-globin genes (including pseudogenes) appearsto differ among species, although highly divergent pseudogenes may not havebeen detected in all species examined. Although matching sequences could befound in interspecies comparisons of the flanking regions of alpha- globingenes, these matches are not as extensive as those found in the flankingregions of mammalian beta-like globin genes. This observation suggests thatthe noncoding sequences in the mammalian alpha-globin gene clusters areevolving at a faster rate than those in the beta-like globin gene clusters.The proposed faster rate of evolution fits with the poor conservation ofthe genetic linkage map around alpha-globin gene clusters when compared tothat of the beta-like globin gene clusters. Analysis of the 3' flankingregions of alpha-globin genes has revealed a conserved sequenceapproximately 100-150 bp 3' to the polyadenylation site; this sequence maybe involved in the expression or regulation of alpha-globin genes.