Advantage or disadvantage of a decrease of blood oxygen affinity for tissue oxygen supply at hypoxia

Turek, Z.; Kreuzer, F.; Hoofd, Louis

doi:10.1007/bf00591367

Cited by 126 publications

(37 citation statements)

References 23 publications

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“…Under conditions of extreme hypoxia, a high hemoglobin-oxygen affinity is generally advantageous because there is a premium on pulmonary oxygen loading at low pO 2 (Turek et al 1973;Hsia 1998;Storz 2007). The physiological trade-off is that high hemoglobin-oxygen affinity hinders the release of oxygen in the tissue capillary beds.…”

Section: Discussionmentioning

confidence: 99%

Adaptive Functional Divergence Among Triplicated α-Globin Genes in Rodents

et al. 2008

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The functional divergence of duplicated genes is thought to play an important role in the evolution of new developmental and physiological pathways, but the role of positive selection in driving this process remains controversial. The objective of this study was to test whether amino acid differences among triplicated a-globin paralogs of the Norway rat (Rattus norvegicus) and the deer mouse (Peromyscus maniculatus) are attributable to a relaxation of purifying selection or to a history of positive selection that has adapted the gene products to new or modified physiological tasks. In each rodent species, the two paralogs at the 59-end of the a-globin gene cluster (HBA-T1 and HBA-T2) are evolving in concert and are therefore identical or nearly identical in sequence. However, in each case, the HBA-T1 and HBA-T2 paralogs are distinguished from the third paralog at the 39-end of the gene cluster (HBA-T3) by multiple amino acid substitutions. An analysis of genomic sequence data from several rodent species revealed that the HBA-T3 genes of Rattus and Peromyscus originated via independent, lineage-specific duplication events. In the independently derived HBA-T3 genes of both species, a likelihood analysis based on a codon-substitution model revealed that accelerated rates of amino acid substitution are attributable to positive directional selection, not to a relaxation of purifying selection. As a result of functional divergence among the triplicated a-globin genes in Rattus and Peromyscus, the red blood cells of both rodent species contain a mixture of functionally distinct a-chain hemoglobin isoforms that are predicted to have different oxygen-binding affinities. In P. maniculatus, a species that is able to sustain physiological function under conditions of chronic hypoxia at high altitude, the coexpression of distinct hemoglobin isoforms with graded oxygen affinities is expected to broaden the permissible range of arterial oxygen tensions for pulmonary/tissue oxygen transport.

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Section: Discussionmentioning

confidence: 99%

Adaptive Functional Divergence Among Triplicated α-Globin Genes in Rodents

et al. 2008

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“…Under conditions of moderate hypoxia, a reduction in Hb-O 2 affinity can enhance levels of tissue oxygenation by maximizing the capillary-tissue P O2 difference. However, under conditions of severe hypoxia when Pa O2 is substantially reduced, a leftward shift of the O 2 -equilibrium curve is required to allow O 2 loading and unloading over the steepest portion of the curve (Turek et al, 1973;Turek et al, 1978a;Turek et al, 1978b;Samaja et al, 1986;Samaja et al, 2003). Even at low altitude, a left-shifted curve might be advantageous when the rate of O 2 transfer across the blood-gas interface is diffusion limited, as is the case during intense exercise (Bencowitz et al, 1982).…”

Section: Blood-o 2 Affinitymentioning

confidence: 99%

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

Storz

Scott

Cheviron

2010

Journal of Experimental Biology

346

343

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SummaryHigh-altitude environments provide ideal testing grounds for investigations of mechanism and process in physiological adaptation. In vertebrates, much of our understanding of the acclimatization response to high-altitude hypoxia derives from studies of animal species that are native to lowland environments. Such studies can indicate whether phenotypic plasticity will generally facilitate or impede adaptation to high altitude. Here, we review general mechanisms of physiological acclimatization and genetic adaptation to high-altitude hypoxia in birds and mammals. We evaluate whether the acclimatization response to environmental hypoxia can be regarded generally as a mechanism of adaptive phenotypic plasticity, or whether it might sometimes represent a misdirected response that acts as a hindrance to genetic adaptation. In cases in which the acclimatization response to hypoxia is maladaptive, selection will favor an attenuation of the induced phenotypic change. This can result in a form of cryptic adaptive evolution in which phenotypic similarity between high-and low-altitude populations is attributable to directional selection on genetically based trait variation that offsets environmentally induced changes. The blunted erythropoietic and pulmonary vasoconstriction responses to hypoxia in Tibetan humans and numerous high-altitude birds and mammals provide possible examples of this phenomenon. When lowland animals colonize high-altitude environments, adaptive phenotypic plasticity can mitigate the costs of selection, thereby enhancing prospects for population establishment and persistence. By contrast, maladaptive plasticity has the opposite effect. Thus, insights into the acclimatization response of lowland animals to high-altitude hypoxia can provide a basis for predicting how altitudinal range limits might shift in response to climate change.

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“…For example, a reduced erythrocytic concentration of DPG would produce an increased blood-O 2 affinity that helps safeguard arterial O 2 saturation under hypoxia, and this could be reversed upon a return to normoxic conditions. Under conditions of severe hypoxia, theoretical and experimental results indicate that it is generally advantageous to have an elevated blood-O 2 affinity because of the increased premium on pulmonary O 2 loading (Turek et al, 1973;Eaton et al, 1974;Turek et al, 1978a;Turek et al, 1978b;Bouverot, 1985;Samaja et al, 1986;Samaja et al, 2003;Scott and Milsom, 2006). Consistent with this expectation, elevated blood-O 2 affinities are commonly recorded in terrestrial vertebrates that are native to high altitude environments, and in subterranean mammals that cope with the hypoxic and hypercapnic conditions of closed burrow systems (Jelkmann et al,CA, USA (-60m), and also on the summits of the highest peaks in the Sierra Nevada and Rocky Mountains (4350m) where the partial pressure of O 2 (P O2 ) is less than 60% of the sea level value.…”

Section: Introductionmentioning

confidence: 99%

Genetic differences in hemoglobin function between highland and lowland deer mice

Storz

Runck

Moriyama

et al. 2010

Journal of Experimental Biology

126

173

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SUMMARY In high-altitude vertebrates, adaptive changes in blood–O2 affinity may be mediated by modifications of hemoglobin (Hb) structure that affect intrinsic O2 affinity and/or responsiveness to allosteric effectors that modulate Hb–O2 affinity. This mode of genotypic specialization is considered typical of mammalian species that are high-altitude natives. Here we investigated genetically based differences in Hb–O2 affinity between highland and lowland populations of the deer mouse (Peromyscus maniculatus), a generalist species that has the broadest altitudinal distribution of any North American mammal. The results of a combined genetic and proteomic analysis revealed that deer mice harbor a high level of Hb isoform diversity that is attributable to allelic polymorphism at two tandemly duplicated α-globin genes and two tandemly duplicated β-globin genes. This high level of isoHb diversity translates into a correspondingly high level of interindividual variation in Hb functional properties. O2 equilibrium experiments revealed that the Hbs of highland mice exhibit slightly higher intrinsic O2 affinities and significantly lower Cl– sensitivities relative to the Hbs of lowland mice. The experiments also revealed distinct biochemical properties of deer mouse Hb related to the anion-dependent allosteric regulation of O2 affinity. In conjunction with previous findings, our results demonstrate that modifications of Hb structure that alter allosteric anion sensitivity play an important role in the adaptive fine-tuning of blood–O2 affinity.

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Advantage or disadvantage of a decrease of blood oxygen affinity for tissue oxygen supply at hypoxia

Cited by 126 publications

References 23 publications

Adaptive Functional Divergence Among Triplicated α-Globin Genes in Rodents

Adaptive Functional Divergence Among Triplicated α-Globin Genes in Rodents

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

Genetic differences in hemoglobin function between highland and lowland deer mice

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