scholarly journals Ontogenesis of evolved changes in respiratory physiology in deer mice native to high altitude

2020 ◽  
Vol 223 (5) ◽  
pp. jeb219360 ◽  
Author(s):  
Catherine M. Ivy ◽  
Mary A. Greaves ◽  
Elizabeth D. Sangster ◽  
Cayleih E. Robertson ◽  
Chandrasekhar Natarajan ◽  
...  
Keyword(s):  
High Altitude ◽  
Respiratory Physiology ◽  
Deer Mice

scholarly journals Genetic variation in haemoglobin alters breathing in high-altitude deer mice

2021 ◽  
Author(s):  
Catherine M. Ivy ◽  
Oliver H. Wearing ◽  
Chandrasekhar Natarajan ◽  
Rena M. Schweizer ◽  
Natalia Gutiérrez-Pinto ◽  
...  
Keyword(s):  
Genetic Variation ◽  
High Altitude ◽  
Globin Gene ◽  
Respiratory Physiology ◽  
Deer Mice ◽  
Emergent Properties ◽  
Mixed Genetic Background ◽  
Hypoxia Adaptation ◽  
Globin Gene Expression

ABSTRACTPhysiological systems often have emergent properties but the effects of genetic variation on physiology are often unknown, which presents a major challenge to understanding the mechanisms of phenotypic evolution. We investigated the in vivo effects on respiratory physiology of genetic variants in haemoglobin (Hb) that contribute to hypoxia adaptation in high-altitude deer mice (Peromyscus maniculatus). We created F2 inter-population hybrids of highland and lowland deer mice to test the phenotypic effects of α- and β-globin variants on a mixed genetic background. High-altitude genotypes were associated with breathing phenotypes that enhance O2 uptake in hypoxia, including a deeper more effective breathing pattern and an augmented hypoxic ventilatory response. These effects could not be explained by erythrocyte Hb-O2 affinity or globin gene expression in the brainstem. Therefore, adaptive variation in haemoglobin can have unexpected effects on physiology that are distinct from the canonical function of this protein in circulatory O2 transport.

scholarly journals Life-long exposure to hypoxia affects metabolism and respiratory physiology across life stages in high-altitude deer mice (Peromyscus maniculatus)

2020 ◽  
Vol 224 (1) ◽  
pp. jeb237024 ◽  
Author(s):  
Catherine M. Ivy ◽  
Graham R. Scott
Keyword(s):  
High Altitude ◽  
Peromyscus Maniculatus ◽  
Adult Life ◽  
Respiratory Physiology ◽  
Deer Mice ◽  
Continuous Exposure ◽  
Life Stages ◽  
Hypoxia Exposure ◽  
In Captivity ◽  
Haemoglobin Content

ABSTRACTHypoxia exposure can have distinct physiological effects between early developmental and adult life stages, but it is unclear how the effects of hypoxia may progress during continuous exposure throughout life. We examined this issue in deer mice (Peromyscus maniculatus) from a population native to high altitude. Mice were bred in captivity in one of three treatment groups: normoxia (controls), life-long hypoxia (∼12 kPa O2 from conception to adulthood) and parental hypoxia (normoxia from conception to adulthood, but parents previously exposed to hypoxia). Metabolic, thermoregulatory and ventilatory responses to progressive stepwise hypoxia and haematology were then measured at post-natal day (P) 14 and 30 and/or in adulthood. Life-long hypoxia had consistent effects across ages on metabolism, attenuating the declines in O2 consumption rate (V̇O2) and body temperature during progressive hypoxia compared with control mice. However, life-long hypoxia had age-specific effects on breathing, blunting the hypoxia-induced increases in air convection requirement (quotient of total ventilation and V̇O2) at P14 and P30 only, but then shifting breathing pattern towards deeper and/or less frequent breaths at P30 and adulthood. Hypoxia exposure also increased blood–O2 affinity at P14 and P30, in association with an increase in arterial O2 saturation in hypoxia at P30. In contrast, parental hypoxia had no effects on metabolism or breathing, but it increased blood–O2 affinity and decreased red cell haemoglobin content at P14 (but not P30). Therefore, hypoxia exposure has some consistent effects across early life and adulthood, and some other effects that are unique to specific life stages.

scholarly journals FUNCTIONAL GENOMICS OF ADAPTATION TO HYPOXIC COLD-STRESS IN HIGH-ALTITUDE DEER MICE: TRANSCRIPTOMIC PLASTICITY AND THERMOGENIC PERFORMANCE

Evolution ◽  
2013 ◽  
Vol 68 (1) ◽  
pp. 48-62 ◽  
Author(s):  
Zachary A. Cheviron ◽  
Alex D. Connaty ◽  
Grant B. McClelland ◽  
Jay F. Storz
Keyword(s):  
Cold Stress ◽  
Functional Genomics ◽  
High Altitude ◽  
Deer Mice

Low P50 in deer mice native to high altitude

1985 ◽  
Vol 58 (1) ◽  
pp. 193-199 ◽  
Author(s):  
L. R. Snyder
Keyword(s):  
High Altitude ◽  
Significant Negative Correlation ◽  
Deer Mice ◽  
Hypoxic Stress ◽  
Hemoglobin Saturation ◽  
Partial Pressures ◽  
Theoretical Predictions ◽  
Low Altitude ◽  
The Difference

Whereas it is widely believed that animals native to high altitude show lower O2 partial pressures at 50% hemoglobin saturation (P50) than do related animals native to low altitude, that “fact” has not been well documented. Consequently, P50 at pH 7.4, PCO2(7.4), the CO2 Bohr effect, and the buffer slope (delta log PCO2/delta pH) were determined via the mixing technique in Peromyscus maniculatus native to a range of altitudes but acclimated to 340 or 3,800 m. PCO2(7.4) and buffer slope were substantially lower at high altitude. The change in P50(7.4) between acclimation altitudes was minimal (0.8% increase at 3,800 m), because of counterbalancing changes in PCO2, 2,3-diphospho-D-glycerate concentration, and perhaps other factors. At both acclimation altitudes there was a highly significant negative correlation between P50(7.4) and native altitude. Since pH in vivo probably increases slightly at high altitude, the data on P50 corrected to pH 7.4 are probably underestimates of the difference in in vivo P50 at low vs. high altitude. Hence these results corroborate theoretical predictions that low P50 is advantageous under severe hypoxic stress.

scholarly journals Plasticity of non-shivering thermogenesis and brown adipose tissue in high-altitude deer mice

2021 ◽  
Author(s):  
Soren Z. Coulson ◽  
Cayleih E. Robertson ◽  
Sajeni Mahalingam ◽  
Grant B. McClelland
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Altitude ◽  
Heat Production ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Deer Mice ◽  
Brown Adipose ◽  
Hypoxia Acclimation ◽  
Shivering Thermogenesis

High altitude environments challenge small mammals with persistent low ambient temperatures that require high rates of aerobic heat production in face of low O2 availability. An important component of thermogenic capacity in rodents is non-shivering thermogenesis (NST) mediated by uncoupled mitochondrial respiration in brown adipose tissue (BAT). NST is plastic, and capacity for heat production increases with cold acclimation. However, in lowland native rodents, hypoxia inhibits NST in BAT. We hypothesize that highland deer mice (Peromyscus maniculatus) overcome the hypoxic inhibition of NST through changes in BAT mitochondrial function. We tested this hypothesis using lab born and raised highland and lowland deer mice, and a lowland congeneric (P. leucopus), acclimated to either warm normoxia (25°C, 760 mmHg) or cold hypoxia (5°C, 430 mmHg). We determined the effects of acclimation and ancestry on whole-animal rates of NST, the mass of interscapular BAT (iBAT), and uncoupling protein (UCP)-1 protein expression. To identify changes in mitochondrial function, we conducted high-resolution respirometry on isolated iBAT mitochondria using substrates and inhibitors targeted to UCP-1. We found that rates of NST increased with cold hypoxia acclimation but only in highland deer mice. There was no effect of cold hypoxia acclimation on iBAT mass in any group, but highland deer mice showed increases in UCP-1 expression and UCP-1 stimulated mitochondrial respiration in response to these stressors. Our results suggest that highland deer mice have evolved to increase the capacity for NST in response to chronic cold hypoxia, driven in part by changes in iBAT mitochondrial function.

Lipid Oxidation during Thermogenesis in High-Altitude Deer Mice (Peromyscus maniculatus)

2021 ◽  
Author(s):  
Sulayman Aslan Lyons ◽  
Kevin B Tate ◽  
Kenneth Collins Welch ◽  
Grant B. McClelland
Keyword(s):  
Lipid Oxidation ◽  
Palmitic Acid ◽  
High Altitude ◽  
Deer Mice ◽  
Acid Oxidation ◽  
Cold Environments ◽  
Oxidation Rates ◽  
Low Altitude ◽  
Land Mammal ◽  
Specific Lipid

When at their maximum thermogenic capacity (cold-induced V̇O2max), small endotherms reach levels of aerobic metabolism as high, or even higher, than running V̇O2max. How these high rates of thermogenesis are supported by substrate oxidation is currently unclear. The appropriate utilization of metabolic fuels that could sustain thermogenesis over extended periods may be important for survival in cold environments, like high altitude. Previous studies show that high capacities for lipid use in high-altitude deer mice may have evolved in concert with greater thermogenic capacities. The purpose of this study was to determine how lipid utilization at both moderate and maximal thermogenic intensities may differ in high- and low- altitude deer mice, and strictly low-altitude white-footed mice. We also examined the phenotypic plasticity of lipid use after acclimation to cold hypoxia (CH), conditions simulating high altitude. We found that lipids were the primary fuel supporting both moderate and maximal rates of thermogenesis in both species of mice. Lipid oxidation increased 3-fold in mice from 30oC to 0oC, consistent with increases in oxidation of [13C]-palmitic acid. CH acclimation led to an increase in [13C]-palmitic acid oxidation at 30oC but did not affect total lipid oxidation. Lipid oxidation rates at cold-induced V̇O2max were two- to four-fold those at 0oC and increased further after CH acclimation, especially in high-altitude deer mice. These are the highest mass-specific lipid oxidation rates observed in any land mammal. Uncovering the mechanisms that allow for these high rates of oxidation will aid our understanding of the regulation of lipid metabolism.

scholarly journals High-altitude rodents have abundant collaterals that protect against tissue injury after cerebral, coronary and peripheral artery occlusion

2020 ◽  
pp. 0271678X2094260
Author(s):  
James E Faber ◽  
Jay F Storz ◽  
Zachary A Cheviron ◽  
Hua Zhang
Keyword(s):  
High Altitude ◽  
Guinea Pigs ◽  
Prolonged Exposure ◽  
Tissue Injury ◽  
Atmospheric Oxygen ◽  
Arterial Occlusion ◽  
Oxygen Demand ◽  
Artery Occlusion ◽  
Deer Mice ◽  
Collateral Arteries

Collateral number/density varies widely in brain and other tissues among strains of Mus musculus mice due to differences in genetic background. Recent studies have shown that prolonged exposure to reduced atmospheric oxygen induces additional collaterals to form, suggesting that natural selection may favor increased collaterals in populations native to high-altitude. High-altitude guinea pigs ( Cavia) and deer mice ( Peromyscus) were compared with lowland species of Peromyscus, Mus and Rattus (9 species/strains examined). Collateral density, diameter and other morphometrics were measured in brain where, importantly, collateral abundance reflects that in other tissues of the same individual. Guinea pigs and high-altitude deer mice had a greater density of pial collaterals than lowlanders. Consistent with this, guinea pigs and highlander mice evidenced complete and 80% protection against stroke, respectively. They also sustained significantly less ischemia in heart and lower extremities after arterial occlusion. Vessels of the circle of Willis, including the communicating collateral arteries, also exhibited unique features in the highland species. Our findings support the hypothesis that species native to high-altitude have undergone genetic selection for abundant collaterals, suggesting that besides providing protection in obstructive disease, collaterals serve a physiological function to optimize oxygen delivery to meet oxygen demand when oxygen is limiting.

scholarly journals Development of homeothermic endothermy is delayed in high-altitude native deer mice ( Peromyscus maniculatus)

2019 ◽  
Vol 286 (1907) ◽  
pp. 20190841 ◽  
Author(s):  
Cayleih E. Robertson ◽  
Glenn J. Tattersall ◽  
Grant B. McClelland
Keyword(s):  
High Altitude ◽  
Peromyscus Maniculatus ◽  
Common Garden ◽  
Deer Mice ◽  
Ambient Temperatures ◽  
Equivalent Age ◽  
Brown Adipose ◽  
Challenging Environment ◽  
Sympathetic Regulation ◽  
Saving Measure

Altricial mammals begin to independently thermoregulate during the first few weeks of postnatal development. In wild rodent populations, this is also a time of high mortality (50–95%), making the physiological systems that mature during this period potential targets for selection. High altitude (HA) is a particularly challenging environment for small endotherms owing to unremitting low O 2 and ambient temperatures. While superior thermogenic capacities have been demonstrated in adults of some HA species, it is unclear if selection has occurred to survive these unique challenges early in development. We used deer mice ( Peromyscus maniculatus ) native to high and low altitude (LA), and a strictly LA species ( Peromyscus leucopus ), raised under common garden conditions, to determine if postnatal onset of endothermy and maturation of brown adipose tissue (BAT) is affected by altitude ancestry. We found that the onset of endothermy corresponds with the maturation and activation of BAT at an equivalent age in LA natives, with 10-day-old pups able to thermoregulate in response to acute cold in both species. However, the onset of endothermy in HA pups was substantially delayed (by approx. 2 days), possibly driven by delayed sympathetic regulation of BAT. We suggest that this delay may be part of an evolved cost-saving measure to allow pups to maintain growth rates under the O 2 -limited conditions at HA.

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