Evolution of the globin superfamily and its function

Abstract

Bacterial hemoglobins (Hbs) are ancient proteins, found in approximately two thirds of presently known bacterial genomes (>800), clearly related to the familiar vertebrate myoglobins,α- and β-globins and the recently discovered neuroglobins and cytoglobins. All bacterial Hbs belong to one of three families: the flavohemoglobins (F) and sensor (S) globins, that display the canonical 3/3 α-helical fold characteristic of the metazoan Hbs, and the 2/2 (“truncated”) Hbs (T), that exhibit a shortened 2/2 α-helical fold. The F family comprises single domain globins and chimeric, -400aa proteins with C-terminal ferredoxin reductase-like domain. The S family consists of single domain globins and chimeric proteins with variable (300-700aa) C-terminal domain(s)involved in chemotaxis and gene regulation. Because eukaryote globins appear to be most similar to members of the bacterial F family, we have proposed that one or more horizontal transfer(s) of single domain FHb-like gene(s) to ancestor(s) of multicellular eukaryotes could have accompanied the endosymbiotic events responsible for the origins of mitochondria and plastids, and provided the precursor(s) of all the eukaryote Hbs, at some time prior to the emergence of multicellularity, about 1,000 to 650 Myrs ago. Within this framework, the probable early bacterial Hb functions, oxygen binding and sensing and enzymatic reactions with nitric oxide, were preserved in bacteria and eukaryotes. The emergence of multicellularity and the evolution of crown eukaryotes (plants, fungi and metazoans) and numerous unicellular eukaryote groups, was accompanied by an expansion and diversification of globin functions, mostly not well understood at present. Apart from reversible oxygen binding, enabling control of oxygen concentration and the storage and transport of oxygen, these include NO dioxygenase and nitrite reductase activities, oxygen sensing, reactions with free radicals and specific adaptations exemplified by reversible sulfide binding and transport and chloroperoxidase activity. Because multicellularity emerged more than once, it is likely that each event was accompanied by differential spreading of the three globin families in eukaryotes, resulting in the selection of globins best suited to assist in the survival of the emerging eukaryote. Of the three bacterial globin families, the S and T families spread only to the fungi and plants, respectively, and some unicellular eukaryotes. In contrast, the single domain globins from the F family spread widely among eukaryotes, particularly the crown eukaryotes, likely due to the plasticity of their structures that allowed subtle diversification of their functions. Overall, the globin superfamily has displayed unsuspected versatility and extraordinary success in evolving from useful but dispensable proteins in a majority of prokaryotes, to ubiquitous indispensability in the crown eukaryotes.