TY - JOUR
T1 - Molecular basis of a novel adaptation to hypoxic-hypercapnia in a strictly fossorial mole
AU - Campbell, Kevin L.
AU - Storz, Jay F.
AU - Signore, Anthony V.
AU - Moriyama, Hideaki
AU - Catania, Kenneth C.
AU - Payson, Alexander P.
AU - Bonaventura, Joseph
AU - Stetefeld, Jörg
AU - Weber, Roy E.
N1 - Funding Information:
We thank R. Gusztak and S.T. Sheehan for aid in procuring blood samples and A. Bang for technical support. M. Krogh Larsen, A. Sloan and J. Howatt provided valuable assistance with gene sequencing, while N. Lovejoy, G. Valdimarsson and O. Westergaard kindly provided lab space and equipment for components of this work. This research was supported by grants from the Natural Sciences and Engineering Research Council (NSERC) of Canada (KLC, JS), the National Institutes of Health (JFS), the National Science Foundation (JFS), the Nebraska Tobacco Settlement Biomedical Research Development Fund (HM), the Danish Natural Science Research Council (REW), and the Carlsberg Foundation (REW).
PY - 2010
Y1 - 2010
N2 - Background. Elevated blood O2affinity enhances survival at low O2pressures, 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 O2affinity 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 2affinity, 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 -type -globin chain (136GlyGlu) of this species that perturbs electrostatic interactions between the dimer subunits via formation of an intra-chain salt-bridge with 82Lys. 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 82Lys, thereby markedly reducing competition for carbamate formation (CO2binding) at the -chain N-termini. Conclusions. We propose this Hb phenotype illustrates a novel mechanism for adaptively elevating the CO 2carrying capacity of eastern mole blood during burst tunnelling activities associated with subterranean habitation.
AB - Background. Elevated blood O2affinity enhances survival at low O2pressures, 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 O2affinity 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 2affinity, 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 -type -globin chain (136GlyGlu) of this species that perturbs electrostatic interactions between the dimer subunits via formation of an intra-chain salt-bridge with 82Lys. 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 82Lys, thereby markedly reducing competition for carbamate formation (CO2binding) at the -chain N-termini. Conclusions. We propose this Hb phenotype illustrates a novel mechanism for adaptively elevating the CO 2carrying capacity of eastern mole blood during burst tunnelling activities associated with subterranean habitation.
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U2 - 10.1186/1471-2148-10-214
DO - 10.1186/1471-2148-10-214
M3 - Article
C2 - 20637064
AN - SCOPUS:77954550402
SN - 1471-2148
VL - 10
JO - BMC Evolutionary Biology
JF - BMC Evolutionary Biology
IS - 1
M1 - 214
ER -