title: Molecular basis of a novel adaptation to hypoxic-hypercapnia in a strictly fossorial mole.
abstract: BACKGROUND
  Elevated blood O(2) affinity enhances survival at low O(2) pressures, and is perhaps the best known and most broadly accepted evolutionary adjustment of terrestrial vertebrates to environmental hypoxia. This phenotype arises by increasing the intrinsic O(2) affinity of the hemoglobin (Hb) molecule, by decreasing the intracellular concentration of allosteric effectors (e.g., 2,3-diphosphoglycerate; DPG), or by suppressing the sensitivity of Hb to these physiological cofactors.
  
  
  RESULTS
  Here we report that strictly fossorial eastern moles (Scalopus aquaticus) have evolved a low O(2) affinity, DPG-insensitive Hb - contrary to expectations for a mammalian species that is adapted to the chronic hypoxia and hypercapnia of subterranean burrow systems. Molecular modelling indicates that this functional shift is principally attributable to a single charge altering amino acid substitution in the beta-type delta-globin chain (delta136Gly-->Glu) of this species that perturbs electrostatic interactions between the dimer subunits via formation of an intra-chain salt-bridge with delta82Lys. However, this replacement also abolishes key binding sites for the red blood cell effectors Cl-, lactate and DPG (the latter of which is virtually absent from the red cells of this species) at delta82Lys, thereby markedly reducing competition for carbamate formation (CO(2) binding) at the delta-chain N-termini.
  
  
  CONCLUSIONS
  We propose this Hb phenotype illustrates a novel mechanism for adaptively elevating the CO(2) carrying capacity of eastern mole blood during burst tunnelling activities associated with subterranean habitation.
authors.affiliation: Department of Biological Sciences, University of Manitoba, Winnipeg, Canada. campbelk@cc.umanitoba.ca
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Campbell
authors.forename: Jay F
authors.initials: JF
authors.lastname: Storz
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Signore
authors.forename: Hideaki
authors.initials: H
authors.lastname: Moriyama
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Catania
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Payson
authors.forename: Joseph
authors.initials: J
authors.lastname: Bonaventura
authors.forename: Jörg
authors.initials: J
authors.lastname: Stetefeld
authors.forename: Roy E
authors.initials: RE
authors.lastname: Weber
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D015723:Gene Library; D006454:Hemoglobins / Q000235:genetics*; D006935:Hypercapnia / Q000235:genetics*; D000860:Hypoxia / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008971:Moles / Q000235:genetics*; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D006454:Hemoglobins; D020033:Protein Isoforms; D002245:Carbon Dioxide; D010100:Oxygen