title: Molecular Evolution of the Oxygen-Binding Hemerythrin Domain.
abstract: BACKGROUND
  The evolution of oxygenic photosynthesis during Precambrian times entailed the diversification of strategies minimizing reactive oxygen species-associated damage. Four families of oxygen-carrier proteins (hemoglobin, hemerythrin and the two non-homologous families of arthropodan and molluscan hemocyanins) are known to have evolved independently the capacity to bind oxygen reversibly, providing cells with strategies to cope with the evolutionary pressure of oxygen accumulation. Oxygen-binding hemerythrin was first studied in marine invertebrates but further research has made it clear that it is present in the three domains of life, strongly suggesting that its origin predated the emergence of eukaryotes.
  
  
  RESULTS
  Oxygen-binding hemerythrins are a monophyletic sub-group of the hemerythrin/HHE (histidine, histidine, glutamic acid) cation-binding domain. Oxygen-binding hemerythrin homologs were unambiguously identified in 367/2236 bacterial, 21/150 archaeal and 4/135 eukaryotic genomes. Overall, oxygen-binding hemerythrin homologues were found in the same proportion as single-domain and as long protein sequences. The associated functions of protein domains in long hemerythrin sequences can be classified in three major groups: signal transduction, phosphorelay response regulation, and protein binding. This suggests that in many organisms the reversible oxygen-binding capacity was incorporated in signaling pathways. A maximum-likelihood tree of oxygen-binding hemerythrin homologues revealed a complex evolutionary history in which lateral gene transfer, duplications and gene losses appear to have played an important role.
  
  
  CONCLUSIONS
  Hemerythrin is an ancient protein domain with a complex evolutionary history. The distinctive iron-binding coordination site of oxygen-binding hemerythrins evolved first in prokaryotes, very likely prior to the divergence of Firmicutes and Proteobacteria, and spread into many bacterial, archaeal and eukaryotic species. The later evolution of the oxygen-binding hemerythrin domain in both prokaryotes and eukaryotes led to a wide variety of functions, ranging from protection against oxidative damage in anaerobic and microaerophilic organisms, to oxygen supplying to particular enzymes and pathways in aerobic and facultative species.
authors.affiliation: Facultad de Ciencias, Universidad Nacional Autónoma de México, Apdo. Postal 70-407, Cd. Universitaria, 04510, Mexico City, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: Alvarez-Carreño
authors.affiliation: Facultad de Ciencias, Universidad Nacional Autónoma de México, Apdo. Postal 70-407, Cd. Universitaria, 04510, Mexico City, Mexico.
authors.forename: Arturo
authors.initials: A
authors.lastname: Becerra
authors.affiliation: Facultad de Ciencias, Universidad Nacional Autónoma de México, Apdo. Postal 70-407, Cd. Universitaria, 04510, Mexico City, Mexico.|Miembro de El Colegio Nacional, Ciudad de México, México.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lazcano
mesh_terms: D000595:Amino Acid Sequence; D016000:Cluster Analysis; D019143:Evolution, Molecular; D018628:Gene Dosage; D016680:Genome, Bacterial; D006422:Hemerythrin / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010802:Phylogeny; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs
chemical_list: D006422:Hemerythrin; D010100:Oxygen