Sequence and comparative analysis of the rabbit α-like globin gene cluster reveals a rapid mode of evolution in a G + C-rich region of mammalian genomes

Abstract

A sequence of 10,621 base-pairs from the α-like globin gene cluster of rabbit has been determined. It includes the sequence of gene ζ (a pseudogene for the rabbit embryonic ζ-globin), the functional rabbit α-globin gene, and the θ1 psuedogene, along with the sequences of eight C repeats (short interspersed repeats in rabbit) and a J sequence implicated in recombination. The region is quite G + C-rich (62%) and contains two CpG islands. As expected for a very G + C-rich region, it has an abundance of open reading frames, but few of the long open reading frames are associated with the coding regions of genes. Alignments between the sequences of the rabbit and human α-like globin gene clusters reveal matches primarily in the immediate vicinity of genes and CpG islands, while the intergenic regions of these gene clusters have many fewer matches than are seen between the β-like globin gene clusters of these two species. Furthermore, the non-coding sequences in this portion of the rabbit α-like globin gene cluster are shorter than in human, indicating a strong tendency either for sequence contraction in the rabbit gene cluster or for expansion in the human gene cluster. Thus, the intergenic regions of the α-like globin gene clusters have evolved in a relatively fast mode since the mammalian radiation, but not exclusively by nucleotide substitution. Despite this rapid mode of evolution, some strong matches are found 5′ to the start sites of the human and rabbit α genes, perhaps indicating conservation of a regulatory element. The rabbit J sequence is over 1000 base-pairs long; it contains a C repeat at its 5′ end and an internal region of homology to the 3′-untranslated region of the α-globin gene. Part of the rabbit J sequence matches with sequences within the X homology block in human. Both of these regions have been implicated as hot-spots for recombination, hence the matching sequences are good candidates for such a function. All the interspersed repeats within both gene clusters are retroposon SINEs that appear to have inserted independently in the rabbit and human lineages.