BIOCHEMISTRY OF INVERTEBRATE HEMOGLOBINS

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Hemoglobins are widely but sporadically distributed in most invertebrate phyla. Most of these hemoglobins have 15-17 kDa chains and are either intracellular (molecules < 65 kDa) or extracellular with masses to 8000 kDa. Some arthropods and molluscs have hemoglobins with chains composed of 2 to 20 myoglobin-like domains joined by peptide bonds. Many of the hemoglobins exhibit highly cooperative O2 binding and are strongly affected by pH. Others are non-cooperative and completely independent of pH. Some have unique functions such as sulfide binding not shared by vertebrate hemoglobins. The modes of assembly and inter-subunit interaction are totally different from those of vertebrate hemoglobins. The extraordinary diversity of both form and function provides an attractive system in which to investigate gene structure, function and evolution as well as protein structure and function. The goal is to understand the relationship between structure and function in selected invertebrate hemoglobins, and to determine the organization and nucleotide sequences of certain clusters of globin genes that have been identified. These systems include the giant, 200-subunit extracellular hemoglobins of the earthworm, Lumbricus, the multi-subunit, multidomain hemoglobins of the molluscs, Barbatia and Cardita and the intriguing flavohemoglobins of ascomycetous fungi and the hydrogen bacterium, Alcaligenes. We seek to determine how the 7 constituent chains of Lumbricus hemoglobin assemble to form a highly cooperative 200 subunit molecule, and how the cooperative O2-binding is modulated by the allosteric modulators, calcium and protons. We will learn, as seems most unlikely, whether the 18 domains of Cardita globin arose by unique RNA-processing events. If the genes of the domain globins show the expected repeating structures, then the differences should indicate a pattern of duplication. Existing data indicate not only that the 18 domains are very similar, but that no significant amino acid spacers occur between them. The gene structure should allow assessment of the possible roles of unequal crossing-over and gene conversion. The leghemoglobin genes of plants have 3 introns and 4 exons in contrast to the genes for vertebrate globins which have only 2 introns. The only invertebrate globin genes now determined are those of the insect larva Chironomus which lacks introns, and a globin gene from the earthworm Lumbricus, the intron/exon organization of which is identical with that of the globin genes of vertebrates. The flavohemoglobins of fungi and bacteria may provide an evolutionary link between cytochromes and hemoglobins. We hope, by determing the structures of selected globin genes of lower invertebrates, to determine the extent of variation of the exon/intron organization and to develop a better understanding of globin evolution.