Sequence and linkage of the goat epsilon I and epsilon II beta-globin genes

Abstract

Overlapping clones containing beta-globin genes have been isolated from a goat genomic library which establish the linkage arrangement 5'-epsilon I-epsilon II-psi beta X-beta C-3'. The complete nucleotide sequence of the epsilon I and epsilon II genes was determined. The sequences of these two genes, along with those previously reported for psi beta X and beta C, complete the sequence of the genes of this linkage set. The first gene in the quadruplet, epsilon I, shows unexpectedly high homology with the human epsilon globin gene both in coding and non-coding regions, and encodes a globin protein that is 90% homologous to human epsilon. The only major difference between the goat epsilon I gene and the human epsilon gene is the presence of an insertion element in the second intron of epsilon I. This element is repetitive in nature and is similar to those found in the second intron of the gamma, beta C and beta A globin genes of the goat. epsilon II also shows high nucleotide homology to the human epsilon globin gene in coding regions and encodes a protein 79% homologous to human epsilon. Notably, however, epsilon II has equivalent nucleotide homology in coding regions to the gamma and epsilon genes of the human locus. The insertion element present in epsilon I is not present in epsilon II. A comparison of the goat beta globin set described here, based on linkage arrangement, nucleotide homology and divergence analysis indicates that this subset of goat beta globin genes is analogous to the entire beta globin loci of other mammalian species. These analyses further indicate that the embryonic genes in these clusters are evolving more slowly than the adult beta globin genes. Comparison of the 5' flanking sequences of epsilon I and epsilon II with those of the beta-embryonic globin genes of other mammals reveals a conserved sequence, C-A-C-C-C-C-T-G, located 28 to 29 bases upstream from the C-C-A-A-T consensus sequence, which appears at this position in the embryonic genes, but in none of the non-embryonic genes. Significantly, this sequence is selectively conserved in the human alpha embryonic globin gene, zeta, which diverged from the beta embryonic genes 500 million years ago, and it may therefore represent an embryonic recognition or signal sequence.