ORGANIZATION OF NONVERTEBRATE GLOBIN GENES

The organization of non-vertebrate globin genes exhibits substantially more variability than the three-exon, two-intron structure of the vertebrate globin genes. (1) The structures of genes of the single-domain globin chains of the annelid Lumbricus and the mollusc Anadara, and the globin gene coding for the two-domain chains of the clam Barbatia, are similar to the vertebrate plan. (2) Genes for single-domain chains exist in bacteria and protozoa. Although the globin gene is highly expressed in the bacterium Vitreoscilla, the putative globin gene hmp in E. coli, which codes for a chimeric protein whose N-terminal moiety of 139 residues contains 67 residues identical to the Vitreoscilla globin. may be either unexpressed or expressed at very low levels, despite the presence of normal regulatory sequences. The DNA sequence of the globin gene of the protozoan Paramecium, determined recently by Yamauchi and collaborators, appears to consist of two exons separated by a short intron. (3) Among the lower eukaryotes, the yeasts Saccharomyces and Candida have chimeric proteins consisting of N-terminal globin and C-terminal flavoprotein moieties of about the same size. The structure of the gene for the chimeric protein of Saccharomyces exhibits no introns. According to Riggs, the presence of chimeric proteins in E. coli and other prokaryotes, such as Alcaligenes and Rhizobium, as well as in yeasts, suggests a previously unrecognized evolutionary pathway for hemoglobin, namely that of a multipurpose heme-binding domain attached to a variety of unrelated proteins with diverse functions. (4) The published globin gene sequences of the insect larva Chironomus have an intron-less structure and are present as clusters of multiple copies; the expression of the globin genes is tissue and developmental stage-specific. Furthermore, the expression of many of these genes has not yet been demonstrated despite the presence of apparently normal regulatory sequences in the two flanking regions. Unexpectedly, Bergtrom and collaborators have recently shown that at least three Ctt globin IIbeta genes contain putative introns. (5) Pohajdak and collaborators have found a seven-exon and six-intron structure for the globin gene of the nematode Pseudoterranova which codes for a two-domain globin chain. Although the second and fourth introns of the N-terminal domain correspond to the two introns found in vertebrate globin genes, the position of the third intron is close to that of the central intron in plant hemoglobins. (6) A four-exon, three-intron structure appears to be general for the genes of plant globins. The latter include the leghemoglobins, globins occurring in legumes (e.g. the four lb loci of the soybean Glycine max), in the highly differentiated structures (nodules) developed in the presence of symbionts (the proteobacteria Rhizobium, Bradyrhizobium and Azorhizobium and the actinomycete Frankia) and the globins present in symbiont-containing non-leguminous plants and in symbiont-free plants. Although the leghemoglobin genes occur in multiple copies at two separate loci, some plants have a single globin gene locus. The lb loci are developmentally expressed at a high level and are regulated in a tissue-specific manner upon induction by the bacterial symbiont. The widespread, if sporadic, occurrence of globin-like genes in diverse groups of living organisms suggests that globin-like genes may be ubiquitous and thus likely to have descended from a single, ancient, globin-like gene coding for a monomeric, single-chain, single-domain globin, which existed prior to the time of divergence of prokaryotes and eukaryotes.