Rh proteins vs Amt proteins: an organismal and phylogenetic perspective on CO2 and NH3 gas channels.
Rh (Rhesus) proteins are homologues of ammonium transport (Amt) proteins. Physiological and structural evidence shows that Amt proteins are gas channels for NH(3), but the substrate of Rh proteins, be it CO2 as shown in green alga, or NH3/NH4+ as shown in mammalian cells, remains disputed. We assembled a large dataset generated of Rh and Amt to explore how Rh originated from and evolved independently of Amt relatives. Analysis of this rich data implies that Rh was split from Amt first to emerge in archaeal species. The Rh ancestor underwent divergence and duplication along speciation, leading to neofunctionalization and subfunctionalization of the Rh family. The characteristic organismal distribution of Rh vs. Amt reflects their early separation and subsequent independent evolution: they coexist in microbes and invertebrates but do not in fungi, vascular plants or vertebrates. Rh gene-duplication was prominent in vertebrates: while epithelial RhBG/RhCG displayed strong purifying selection, erythroid Rh30 and RhAG experienced different episodes of positive selection in each of which adaptive evolution occurred at certain time points and in a few codon sites. Mammalian Rh30 and RhAG were subject to particularly strong positive selection in some codon sites in the lineage from rodents to human. The grounds of this adaptive evolution may be driven by the necessity to increase the surface/volume ratio of biconcave erythrocytes for facilitative gas diffusion. Altogether, these results are consistent with Rh proteins not being the orthologue of Amt proteins but having gained the function for CO2/HCO3- transport, with important roles in systemic pH regulation.
Peng
J
J
Laboratory of Biochemistry and Molecular Genetics, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10021, USA.
Huang
C H
CH
D000595:Amino Acid Sequence; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D001105:Archaea / Q000378:metabolism; D019843:Archaeal Proteins / Q000502:physiology; D001419:Bacteria / Q000378:metabolism; D001426:Bacterial Proteins / Q000502:physiology; D001692:Biological Transport; D001798:Blood Proteins / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000502:physiology*; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000502:physiology; D005658:Fungi / Q000378:metabolism; D020440:Gene Duplication; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D007448:Invertebrates / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology; D026901:Membrane Transport Proteins / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D010940:Plant Proteins / Q000502:physiology; D010944:Plants / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D051381:Rats; D012204:Rh-Hr Blood-Group System / Q000502:physiology*; D012641:Selection, Genetic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013379:Substrate Specificity; D014714:Vertebrates / Q000378:metabolism
C111096:AmtB protein, E coli; D019843:Archaeal Proteins; D001426:Bacterial Proteins; D001798:Blood Proteins; D027682:Cation Transport Proteins; D029968:Escherichia coli Proteins; D005656:Fungal Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D010940:Plant Proteins; D000644:Quaternary Ammonium Compounds; C498523:RHAG protein, human; C422995:RHBG protein, human; C066468:RHCE protein, human; C413213:RHCG protein, human; C508142:Rh type B glycoprotein, rat; C508143:Rh type C glycoprotein, rat; D012204:Rh-Hr Blood-Group System; C486033:RhBG protein, mouse; C401210:Rhag protein, mouse; C498524:Rhag protein, rat; C485880:Rhcg protein, mouse; D002245:Carbon Dioxide; D000641:Ammonia