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Molecular basis of a novel adaptation to hypoxic-hypercapnia in a strictly fossorial mole.

Campbell KL, Storz JF, Signore AV, Moriyama H, Catania KC, Payson AP, Bonaventura J, Stetefeld J, Weber RE - BMC Evol. Biol. (2010)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, University of Manitoba, Winnipeg, Canada. campbelk@cc.umanitoba.ca

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.

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Oxygen equilibration curves of freshly drawn coast (■) eastern (▲) and star-nosed mole (●) blood at 36°C and a PCO2 of 38 mm Hg. Inset: The effect of temperature on the half-saturation pressure (P50) of whole blood of these three species.
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Figure 3: Oxygen equilibration curves of freshly drawn coast (■) eastern (▲) and star-nosed mole (●) blood at 36°C and a PCO2 of 38 mm Hg. Inset: The effect of temperature on the half-saturation pressure (P50) of whole blood of these three species.

Mentions: In accordance with the observed differences in the oxygen affinity of coast vs. eastern mole Hb components in the presence of allosteric effectors (Figure 2), the P50 of freshly drawn coast mole blood (17.7 mm Hg at 36°C) was substantially lower than that from the eastern mole (28.8 mm Hg), while that of the amphibious star-nosed mole was intermediate (22.5 mm Hg; Figure 3, Table 2). However, whole blood pH was notably lower in eastern mole (pH = 7.38) than in the coast and star-nosed moles (7.60 and 7.55, respectively). Even when corrected to pH 7.4, a clear difference in whole-blood O2-affinity of these two fossorial species was evident (P50 = 21.9 vs. 26.9 mm Hg, respectively). The CO2 Bohr coefficients (determined by measurements whereby the pH is changed by varying PCO2) of blood from coast mole (-0.52) and star-nosed mole (-0.40) were within the typical mammalian range (-0.39 to -0.62; [10]), while that of the eastern mole was unusually high (-0.78; Table 2). Consistent with our Hb data, the blood P50 values of both fossorial species showed low temperature sensitivities, with the Hb-oxygenation reaction being less exothermic in coast mole (ΔH=-1.0 kJ mol-1 O2; Table 2) than in the eastern mole (-8.3 kJ mol-1). Surprisingly, blood-O2 affinity of the semi-aquatic star-nosed mole was more strongly governed by temperature (inset of Figure 3), as reflected by its high oxygenation enthalpy (-29.9 kJ mol-1 O2; Table 2) relative to the fossorial mole species.


Molecular basis of a novel adaptation to hypoxic-hypercapnia in a strictly fossorial mole.

Campbell KL, Storz JF, Signore AV, Moriyama H, Catania KC, Payson AP, Bonaventura J, Stetefeld J, Weber RE - BMC Evol. Biol. (2010)

Oxygen equilibration curves of freshly drawn coast (■) eastern (▲) and star-nosed mole (●) blood at 36°C and a PCO2 of 38 mm Hg. Inset: The effect of temperature on the half-saturation pressure (P50) of whole blood of these three species.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927915&req=5

Figure 3: Oxygen equilibration curves of freshly drawn coast (■) eastern (▲) and star-nosed mole (●) blood at 36°C and a PCO2 of 38 mm Hg. Inset: The effect of temperature on the half-saturation pressure (P50) of whole blood of these three species.
Mentions: In accordance with the observed differences in the oxygen affinity of coast vs. eastern mole Hb components in the presence of allosteric effectors (Figure 2), the P50 of freshly drawn coast mole blood (17.7 mm Hg at 36°C) was substantially lower than that from the eastern mole (28.8 mm Hg), while that of the amphibious star-nosed mole was intermediate (22.5 mm Hg; Figure 3, Table 2). However, whole blood pH was notably lower in eastern mole (pH = 7.38) than in the coast and star-nosed moles (7.60 and 7.55, respectively). Even when corrected to pH 7.4, a clear difference in whole-blood O2-affinity of these two fossorial species was evident (P50 = 21.9 vs. 26.9 mm Hg, respectively). The CO2 Bohr coefficients (determined by measurements whereby the pH is changed by varying PCO2) of blood from coast mole (-0.52) and star-nosed mole (-0.40) were within the typical mammalian range (-0.39 to -0.62; [10]), while that of the eastern mole was unusually high (-0.78; Table 2). Consistent with our Hb data, the blood P50 values of both fossorial species showed low temperature sensitivities, with the Hb-oxygenation reaction being less exothermic in coast mole (ΔH=-1.0 kJ mol-1 O2; Table 2) than in the eastern mole (-8.3 kJ mol-1). Surprisingly, blood-O2 affinity of the semi-aquatic star-nosed mole was more strongly governed by temperature (inset of Figure 3), as reflected by its high oxygenation enthalpy (-29.9 kJ mol-1 O2; Table 2) relative to the fossorial mole species.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, University of Manitoba, Winnipeg, Canada. campbelk@cc.umanitoba.ca

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.

Show MeSH
Related in: MedlinePlus