Genomic organization and molecular evolution of the genes for neuroglobin and cytoglobin in the hypoxia-tolerant Israeli mole rat, Spalax carmeli

The genes for the two respiratory proteins neuroglobin (Ngb) and cytoglobin (Cygb) in the subterranean Israeli mole rat Spalax carmeli have been sequenced and compared to other mammals including human. Coding regions of both Spalax genes are highly conserved on the nucleotide and amino acid level. The ratios of non-synonymous to synonymous nucleotide substitutions suggest strong purifying selection acting on Ngb and Cygb in all mammals. Thus, there appears to be no special sequence level adaptation in the two respiratory proteins within the hypoxia-tolerant mole rat. On the genomic level, Spalax Ngb and Cygb gene regions revealed the conserved 4-exon-3-intron structure and conserved CpG-rich islands in the 5′ region. The Spalax Cygb gene promoter contains a conserved hypoxia-responsive transcription factor binding site, indicating a possible up-regulation of Cygb under oxygen deprivation. In Cygb intron 1, we observed a stretch of highly conserved putatively non-coding sequence of yet unknown (regulatory?) importance. In the Spalax Ngb gene, we note the presence of candidate hypoxia-responsive elements, which are not conserved in Ngb of hypoxia-sensitive mammals. Both globin gene regions harbor Spalax-specific simple sequence regions, which might be of adaptive value. We conclude that adaptations for hypoxia in mole rats are most likely to be found in regulatory functions rather than in protein structure.