RESUMO
Investigations into relationships between life-history traits, such as growth rate and energy metabolism, typically focus on basal metabolic rate (BMR). In contrast, investigators rarely examine maximal metabolic rate (MMR) as a relevant metric of energy metabolism, even though it indicates the maximal capacity to metabolize energy aerobically, and hence it might also be important in trade-offs. We studied the relationship between energy metabolism and growth in mice (Mus musculus domesticus Linnaeus) selected for high mass-independent metabolic rates. Selection for high mass-independent MMR increased maximal growth rate, increased body mass at 20 weeks of age, and generally altered growth patterns in both male and female mice. In contrast, there was little evidence that the correlated response in mass-adjusted BMR altered growth patterns. The relationship between mass-adjusted MMR and growth rate indicates that MMR is an important mediator of life histories. Studies investigating associations between energy metabolism and life histories should consider MMR because it is potentially as important in understanding life history as BMR.
Assuntos
Metabolismo Energético , Camundongos/crescimento & desenvolvimento , Camundongos/metabolismo , Animais , Metabolismo Basal , Evolução Biológica , Feminino , MasculinoRESUMO
A recent article by Nespolo and Roff suggests that present-day genetic correlations between resting and maximal metabolic rate do not provide support for the aerobic capacity model for the evolution of endothermy. That conclusion is potentially misleading. The aerobic capacity model makes exacting predictions about genetic architecture. While the presence of a genetic correlation does not support the model per se, the absence of a correlation definitively falsifies the model. Testing for present-day correlations remains a useful endeavor, at least until the model is convincingly falsified or until many attempts to falsify the model fail.
Assuntos
Regulação da Temperatura Corporal/genética , Metabolismo Energético/genética , Modelos Genéticos , AnimaisRESUMO
Both appropriate metabolic rates and sufficient immune function are essential for survival. Consequently, eco-immunologists have hypothesized that animals may experience trade-offs between metabolic rates and immune function. Previous work has focused on how basal metabolic rate (BMR) may trade-off with immune function, but maximal metabolic rate (MMR), the upper limit to aerobic activity, might also trade-off with immune function. We used mice artificially selected for high mass-independent MMR to test for trade-offs with immune function. We assessed (i) innate immune function by quantifying cytokine production in response to injection with lipopolysaccharide and (ii) adaptive immune function by measuring antibody production in response to injection with keyhole limpet haemocyanin. Selection for high mass-independent MMR suppressed innate immune function, but not adaptive immune function. However, analyses at the individual level also indicate a negative correlation between MMR and adaptive immune function. By contrast BMR did not affect immune function. Evolutionarily, natural selection may favour increasing MMR to enhance aerobic performance and endurance, but the benefits of high MMR may be offset by impaired immune function. This result could be important in understanding the selective factors acting on the evolution of metabolic rates.
Assuntos
Imunidade Adaptativa/fisiologia , Evolução Biológica , Imunidade Inata/fisiologia , Animais , Anticorpos/imunologia , Anticorpos/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Metabolismo Energético/imunologia , Feminino , Hemocianinas/imunologia , Hemocianinas/metabolismo , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/farmacologia , CamundongosRESUMO
Aerobic metabolism of vertebrates is linked to membrane fatty acid (FA) composition. Although the membrane pacemaker hypothesis posits that desaturation of FAs accounts for variation in resting or basal metabolic rate (BMR), little is known about the FA profiles that underpin variation in maximal metabolic rate (MMR). We examined membrane FA composition of liver and skeletal muscle in mice after seven generations of selection for increased MMR. In both liver and skeletal muscle, unsaturation index did not differ between control and high-MMR mice. We also examined membrane FA composition at the individual-level of variation. In liver, 18:0, 20:3 n-6, 20:4 n-6, and 22:6 n-3 FAs were significant predictors of MMR. In gastrocnemius muscle, 18:2 n-6, 20:4 n-6, and 22:6 n-3 FAs were significant predictors of MMR. In addition, muscle 16:1 n-7, 18:1 n-9, and 22:5 n-3 FAs were significant predictors of BMR, whereas no liver FAs were significant predictors of BMR. Our findings indicate that (i) individual variation in MMR and BMR appears to be linked to membrane FA composition in the skeletal muscle and liver, and (ii) FAs that differ between selected and control lines are involved in pathways that can affect MMR or BMR.
Assuntos
Metabolismo Basal , Metabolismo Energético , Ácidos Graxos/metabolismo , Membranas/metabolismo , Animais , Peso Corporal , Fígado/metabolismo , Camundongos , Músculo Esquelético/metabolismoRESUMO
Chronic increases in circulating corticosterone (CORT) generally suppress immune function, but it is not known whether evolved increases necessarily have similar adverse effects. Moreover, the evolution of immune function might be constrained by the sharing of signaling molecules, such as CORT, across numerous physiological systems. Laboratory house mice (Mus domesticus Linnaeus) from four replicate lines selectively bred for high voluntary wheel running (HR lines) generally had baseline circulating CORT approximately twofold higher than in four non-selected control (C) lines. To test whether elevated baseline CORT suppresses the inflammatory response in HR mice, we injected females with lipopolysaccharide (LPS). All mice injected with LPS exhibited classic signs of an inflammatory response, including sickness behavior, loss of body mass, reduced locomotor activity (i.e. voluntary wheel running), enlarged spleens and livers, elevated hematocrit and elevated inflammatory cytokines. However, as compared with C mice, the inflammatory response was not suppressed in HR mice. Our results, and those of a previous study, suggest that selective breeding for high voluntary exercise has not altered immune function. They also suggest that the effects of evolved differences in baseline CORT levels may differ greatly from effects of environmental factors (often viewed as 'stressors') that alter baseline CORT during an individual's lifetime. In particular, evolved increases in circulating levels of 'stress hormones' are not necessarily associated with detrimental suppression of the inflammatory response, presumably as a result of correlated evolution of other physiological systems (counter-measures). Our results have important implications for the interpretation of elevated stress hormones and of immune indicators in natural populations.
Assuntos
Condicionamento Físico Animal , Animais , Evolução Biológica , Peso Corporal , Cruzamento , Corticosterona/sangue , Citocinas/metabolismo , Feminino , Hematócrito , Sistema Imunitário/fisiologia , Inflamação , Análise dos Mínimos Quadrados , Lipopolissacarídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/fisiologia , Fenótipo , Corrida , Fatores de TempoRESUMO
There is broad interest in whether there is a tradeoff between energy metabolism and immune function, and how stress affects immune function. Under hypoxic stress, maximal aerobic metabolism is limited, and other aspects of energy metabolism of animals may be altered as well. Although acute hypoxia appears to enhance certain immune responses, the effects of chronic hypoxia on immune function are largely unstudied. We tested: (1) whether chronic hypoxia affects immune function and (2) whether hypoxia affects the metabolic cost of immune function. First, flow cytometry was used to monitor the peripheral blood immunophenotype of mice over the course of 36 days of hypoxic exposure. Second, hypoxic and normoxic mice were subjected to an adaptive immune challenge via keyhole limpet hemocyanin (KLH) or to an innate immune challenge via lipopolysaccharide (LPS). The resting metabolic rates of mice in all immune challenge treatments were also measured. Although hypoxia had little effect on the peripheral blood immunophenotype, hypoxic mice challenged with KLH or LPS had enhanced immunological responses in the form of higher antibody titers or increased TNF-α production, respectively. Initially, mice exposed to hypoxia had lower metabolic rates, but this response was transitory and resting metabolic rates were normal by the end of the experiment. There was no effect of either immune challenge on resting metabolic rate, suggesting that mounting either the acute phase response or a humoral response is not as energetically expensive as previously thought. In addition, our results suggest that immune responses to chronic and acute hypoxia are concordant. Both forms of hypoxia appear to stimulate both innate and adaptive immune responses.
Assuntos
Imunidade Adaptativa/imunologia , Metabolismo Energético/imunologia , Hipóxia/imunologia , Análise de Variância , Animais , Metabolismo Basal , Metabolismo Energético/fisiologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Hemocianinas/imunologia , Imunofenotipagem , Lipopolissacarídeos/imunologia , Camundongos , Fatores de TempoRESUMO
Hypoxia is an important ecological, evolutionary, and biomedical stressor. While physiological acclimatization of mammals to hypoxia is well studied, the variation in gene expression that underlies acclimatization is not well studied. We acclimatized inbred mice for 32 days to hypoxic conditions that simulated altitudes of 1400, 3000, and 4500 m. We used oligonucleotide microarrays to measure changes in steady-state abundance of mRNA in the livers of these mice. Mice exposed to more severe hypoxia (simulated altitude of 4500 m) were smaller in mass and had higher hematocrit than mice exposed to less severe hypoxia. ANOVA and false discovery rate tests indicated that 580 genes were significantly differentially expressed in response to chronic hypoxia. Few of these 580 genes have previously been reported to respond to hypoxia. In contrast, many of these 580 genes belonged to same functional groups typically respond to acute hypoxia. That is, both chronic and acute hypoxia elicit changes in transcript abundance for genes involved in angiogenesis, glycolysis, lipid metabolism, carbohydrate metabolism, and protein amino acid phosphorylation, but the particular genes affected by the two types of hypoxia were mostly different. Numerous genes affecting the immune system were differentially expressed in response to chronic hypoxia, which supports recently proposed hypotheses that link immune function and hypoxia. Furthermore, our results discovered novel elevated mRNA abundance of genes involved in hematopoiesis and oxygen transport not reported previously, but consistent with extreme hematocrits found in hypoxic mice.
Assuntos
Regulação da Expressão Gênica , Hipóxia/genética , Fígado/metabolismo , Fígado/patologia , Animais , Peso Corporal/genética , Doença Crônica , Perfilação da Expressão Gênica , Hematócrito , Células-Tronco Hematopoéticas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Análise de Sequência com Séries de Oligonucleotídeos , Análise de Componente Principal , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos TestesRESUMO
Metabolic rates potentially regulate the pace of important physiological and life-history traits. Natural selection has shaped the evolution of metabolic rates and the physiology that supports them, including digestibility and the rate of food consumption. Understanding the relationship between metabolic rates and energy internalization is central to understanding how resources are allocated among competing physiological functions. We investigated how artificial selection on mass-independent basal metabolic rate (BMR) and mass-independent aerobic maximal metabolic rate (MMR) affected food consumption and apparent digestibility in mice. Evolved changes in mass-corrected BMR-but not mass-corrected MMR-corresponded with changes in food consumption. This result is consistent with previous work showing that BMR constitutes a large portion of an animal's daily energy budget and thus that BMR might provide a better indicator of daily food requirements than MMR. In contrast, digestive efficiencies did not differ among selection treatments and did not evolve in these mice. This study provides insights into how evolution of metabolic rates may affect food consumption and overall energy use.
Assuntos
Metabolismo Basal , Metabolismo Energético , Seleção Genética , Animais , Evolução Biológica , Peso Corporal , Feminino , Masculino , CamundongosRESUMO
The genetic variances and covariances of traits must be known to predict how they may respond to selection and how covariances among them might affect their evolutionary trajectories. We used the animal model to estimate the genetic variances and covariances of basal metabolic rate (BMR) and maximal metabolic rate (MMR) in a genetically heterogeneous stock of laboratory mice. Narrow-sense heritability (h(2)) was approximately 0.38 +/- 0.08 for body mass, 0.26 +/- 0.08 for whole-animal BMR, 0.24 +/- 0.07 for whole-animal MMR, 0.19 +/- 0.07 for mass-independent BMR, and 0.16 +/- 0.06 for mass-independent MMR. All h(2) estimates were significantly different from zero. The phenotypic correlation of whole animal BMR and MMR was 0.56 +/- 0.02, and the corresponding genetic correlation was 0.79 +/- 0.12. The phenotypic correlation of mass-independent BMR and MMR was 0.13 +/- 0.03, and the corresponding genetic correlation was 0.72 +/- 0.03. The genetic correlations of metabolic rates were significantly different from zero, but not significantly different from one. A key assumption of the aerobic capacity model for the evolution of endothermy is that BMR and MMR are linked. The estimated genetic correlation between BMR and MMR is consistent with that assumption, but the genetic correlation is not so high as to preclude independent evolution of BMR and MMR.
Assuntos
Metabolismo Energético/genética , Variação Genética , Aerobiose , Animais , Metabolismo Energético/fisiologia , Camundongos , Atividade Motora/fisiologia , FenótipoRESUMO
The quality of perinatal conditions directly influences the physical and immunological development of nestlings, yet it is inherently variable across space and time. Long-term breeding data for a population of Swainson's hawks (Buteo swainsoni) in northern California show a continuum of territory occupancy and productivity values of individual territories and nests. Here we explore effects of variation among territories on immune system development. We hypothesize that nestlings benefitting from favorable conditions will invest in stronger immune systems, a trait with long-term benefits. We used two immunological assays, a bactericidal assay and a hemolytic-complement activity assay, with leukocyte differentials (heterophilâ¶lymphocyte ratio) to evaluate the constitutive innate immune system. We examined whether early brood-rearing conditions (i.e., number of siblings, hatch date, endoparasite prevalence) were associated with immunological development. Linear mixed-effects models indicated a positive relationship between extended territory occupancy history-an index of habitat quality-and nestling immune function during years with poorer reproduction. There was no association during an exceptionally good reproductive year. Hence, at least under some circumstances, nestling environments or territory characteristics may affect immune function of nestlings. Our study contributes to the growing body of evidence highlighting the importance of facultative allocation to immune traits using long-term demographic data of a top avian predator.
Assuntos
Envelhecimento , Falcões/crescimento & desenvolvimento , Falcões/imunologia , Animais , California , EcossistemaRESUMO
Results of electrophoretic surveys have suggested that hemoglobin polymorphism may be maintained by balancing selection in natural populations of house mice, Mus musculus. Here we report a survey of nucleotide variation in the adult globin genes of house mice from South America. We surveyed nucleotide polymorphism in two closely linked alpha-globin paralogs and two closely linked beta-globin paralogs to test whether patterns of variation are consistent with a model of long-term balancing selection. Surprisingly high levels of nucleotide polymorphism at the two beta-globin paralogs were attributable to the segregation of two highly divergent haplotypes, Hbbs (which carries two identical beta-globin paralogs) and Hbbd (which carries two functionally divergent beta-globin paralogs). Interparalog gene conversion on the Hbbs haplotype has produced a highly unusual situation in which the two paralogs are more similar to one another than either one is to its allelic counterpart on the Hbbd haplotype. Levels of nucleotide polymorphism and linkage disequilibrium at the two beta-globin paralogs suggest a complex history of diversity-enhancing selection that may be responsible for long-term maintenance of alternative protein alleles. The alternative two-locus beta-globin haplotypes are associated with pronounced differences in intraerythrocyte glutathione and nitric oxide metabolism, suggesting a possible mechanism for selection on hemoglobin function.
Assuntos
Conversão Gênica , Genes Duplicados , Globinas/genética , Hemoglobinas/genética , Polimorfismo Genético , Seleção Genética , Animais , Eritrócitos , Globinas/classificação , Glutationa , Haplótipos , Hemoglobinas/classificação , Heterozigoto , Desequilíbrio de Ligação , Camundongos , Camundongos Endogâmicos , Dados de Sequência Molecular , Recombinação Genética , América do SulRESUMO
Biologists often use allometric equations that take the form of power functions (e.g., Y = aM(b), where M stands for mass and a and b are empirically fitted constants). Typically, these allometric equations are fitted by taking the antilog of log-log regressions. Predictions from these allometric equations are biased, and the bias my be appreciable. Methods for making predictions that correct for the bias are available, but they have rarely, if ever, been used by ecological and evolutionary physiologists. Just as physiologists would not use an instrument that was not properly calibrated, they should not use allometric equations to make predictions unless they account for the bias of those predictions. We analyzed 20 interspecific and 10 intraspecific data sets. We compared predictions from standard allometric equations with those from several alternative methods. Our analyses suggest that the bias of predictions from interspecific data sets may be substantial. For the intraspecific data sets we analyzed, the bias was likely to be small. Biologists, including ecological and evolutionary physiologists, should exercise care when using allometric equations to make predictions, particularly given that methods to adjust for bias are easily implemented.
Assuntos
Viés , Interpretação Estatística de Dados , Estatística como Assunto/métodos , Animais , Estatística como Assunto/normasRESUMO
Maximal aerobic metabolic rate (MMR) is an important physiological and ecological variable that sets an upper limit to sustained, vigorous activity. How the oxygen cascade from the external environment to the mitochondria may affect MMR has been the subject of much interest, but little is known about the metabolic profiles that underpin variation in MMR. We tested how seven generations of artificial selection for high mass-independent MMR affected metabolite profiles of two skeletal muscles (gastrocnemius and plantaris) and the liver. MMR was 12.3% higher in mass selected for high MMR than in controls. Basal metabolic rate was 3.5% higher in selected mice than in controls. Artificial selection did not lead to detectable changes in the metabolic profiles from plantaris muscle, but in the liver amino acids and tricarboxylic acid cycle (TCA cycle) metabolites were lower in high-MMR mice than in controls. In gastrocnemius, amino acids and TCA cycle metabolites were higher in high-MMR mice than in controls, indicating elevated amino acid and energy metabolism. Moreover, in gastrocnemius free fatty acids and triacylglycerol fatty acids were lower in high-MMR mice than in controls. Because selection for high MMR was associated with changes in the resting metabolic profile of both liver and gastrocnemius, the result suggests a possible mechanistic link between resting metabolism and MMR. In addition, it is well established that diet and exercise affect the composition of fatty acids in muscle. The differences that we found between control lines and lines selected for high MMR demonstrate that the composition of fatty acids in muscle is also affected by genetic factors.
Assuntos
Metabolismo Basal , Ácidos Graxos/metabolismo , Metaboloma , Camundongos/metabolismo , Animais , Cromatografia Gasosa-Espectrometria de Massas , Fígado/metabolismo , Masculino , Metabolômica , Músculo Esquelético/metabolismoRESUMO
The pelvis is a sexually dimorphic structure and although the causes of that dimorphism have long been studied, relatively little is known regarding the effects of partuitive events on the magnitude of that dimorphism. Here, we use a sample of Mus musculus domesticus to contrast dimorphism in body length and os coxae size and shape between males and parous and nulliparous females. We also test for correlations between relative litter size (L/M) and relative offspring size (O/M) with body length and os coxae size and shape in parous females. Males had greater body length than nulliparous females but were not different from parous females. Females as a whole had the largest os coxae, with parous females having the largest and males the smallest. Os coxae shape was also significantly different between groups and was most divergent between parous females and males than between nulliparous females and males. Os coxae shape differences between females are associated with differences in body length between females and O/M is correlated with os coxae shape in parous females such that females with the largest offspring have the most divergent shapes along the relative warp one axis. Pelvic shape differences between males and females were consistent with previous findings in other taxa which identify the pubo-ischial complex as the primary region of dimorphism.
Assuntos
Paridade , Ossos Pélvicos/anatomia & histologia , Pelve/anatomia & histologia , Animais , Feminino , Masculino , Camundongos , Tamanho do Órgão , Ossos Pélvicos/fisiologia , Pelve/fisiologia , Gravidez , Caracteres SexuaisRESUMO
One of the most important events in vertebrate evolution was the acquisition of endothermy, the ability to use metabolic heat production to elevate body temperature above environmental temperature. Several verbal models have been proposed to explain the selective factors leading to the evolution of endothermy. Of these, the aerobic capacity model has received the most attention in recent years. The aerobic capacity model postulates that selection acted mainly to increase maximal aerobic capacity (or associated behavioral abilities) and that elevated resting metabolic rate evolved as a correlated response. Here we evaluate the implicit evolutionary and genetic assumptions of the aerobic capacity model. In light of this evaluation, we assess the utility of phenotypic and genetic correlations for testing the aerobic capacity model. Collectively, the available intraspecific data for terrestrial vertebrates support the notion of a positive phenotypic correlation between resting and maximal rates of oxygen consumption within species. Interspecific analyses provide mixed support for this phenotypic correlation. We argue, however, that assessments of phenotypic or genetic correlations within species and evolutionary correlations among species (from comparative data) are of limited utility, because they may not be able to distinguish between the aerobic capacity model and plausible alternatives, such as selection acting directly on aspects of thermoregulatory abilities. We suggest six sources of information that may help shed light on the selective factors important during the evolution of high aerobic metabolic rates and, ultimately, the attainment of endothermy. Of particular interest will be attempts to determine, using a combination of mechanistic physiological and quantitative-genetic approaches, whether a positive genetic correlation between resting and maximal rates of oxygen consumption is an ineluctable feature of vertebrate physiology.
RESUMO
Adaptive explanations that rely on physiological arguments are common, but tests of hypotheses about the significance of whole-animal physiological performance (e.g., aerobic capacities) are rare. We studied phenotypic selection on the thermogenic capacity (i.e., maximal rate of oxygen consumption [VO2 max] elicited via cold exposure) of high-altitude (~3800 m) deer mice (Peromyscus maniculatus). A high VO2 max equates to a high capacity for heat production and should favor survival in the cold environments prevalent at high altitude. Strong directional selection favored high VO2 max, at least in one year. The selection for increased VO2 max is consistent with predictions derived from incorporating our physiological data into a biophysical model. During another year, we found weak evidence of selection for decreased body mass. Nonlinear selection was not significant for any of the selection episodes we studied. The strong directional selection for VO2 max that we observed suggests that-given ample genetic variation-aerobic metabolism and perhaps endothermy may have evolved rapidly on the geological time scale.
RESUMO
We tested the hypothesis that locomotor speed and endurance show a negative genetic correlation using a genetically variable laboratory strain of house mice (Hsd:ICR: Mus domesticus). A negative genetic correlation would qualify as an evolutionary "constraint," because both aspects of locomotor performance are generally expected to be under positive directional selection in wild populations. We also tested whether speed or endurance showed any genetic correlation with body mass. For all traits, residuals from multiple regression equations were computed to remove effects of possible confounding variables such as age at testing, measurement block, observer, and sex. Estimates of quantitative genetic parameters were then obtained using Shaw's (1987) restricted maximum-likelihood programs, modified to account for our breeding design, which incorporated cross-fostering. Both speed and endurance were measured on two consecutive trial days, and both were repeatable. We initially analyzed performances on each trial day and the maximal value. For endurance, the three estimates of narrow-sense heritabilities ranged from 0.17 to 0.33 (full ADCE model), and some were statistically significantly different from zero using likelihood ratio tests. The heritability estimate for sprint speed measured on trial day 1 was 0.17, but negative for all other measures. Moreover, the additive genetic covariance between speeds measured on the two days was near zero, indicating that the two measures are to some extent different traits. The additive genetic covariance between speed on trial day 1 and any of the four measures of endurance was negative, large, and always statistically significant. None of the measures of speed or endurance was significantly genetically correlated with body mass. Thus, we predict that artificial selection for increased locomotor speed in these mice would result in a decrease in endurance, but no change in body mass. Such experiments could lead to a better understanding of the physiological mechanisms leading to trade-offs in aspects of locomotor abilities.
RESUMO
In deer mouse (Peromyscus maniculatus) populations in the western United States, alpha-globin haplotype frequency, beta-globin haplotype frequency, and base-line blood oxygen affinity (measured after acclimation to low altitude) show strong correlations with native altitude. The correlations improve when an average regional altitude is substituted for the local altitude at collection sites. This substitution roughly compensates for the effects of gene exchange between populations in areas of highly variable topography. When subspecific effects are removed with covariate analyses a significant (P < 0.05) relationship remains only for alpha-globin haplotype frequency and altitude. Thus, alpha-globin haplotype frequency, beta-globin haplotype frequency, and base-line blood oxygen affinity may be explained by either subspecific or altitudinal effects, but subspecific effects explain a larger proportion of the variance. Part of the subspecific effect may be attributable to an underlying relationship of subspecies with altitude. The analyses for the alpha-globins in conjunction with other data on the effects of alpha-globins on blood oxygen affinity and whole-animal physiological performance are consistent with the hypothesis that the frequency of the alpha-globins evolved in response to selection resulting from the stress of high-altitude hypoxia.
RESUMO
Wild populations of deer mice (Peromyscus maniculatus) contain hemoglobin polymorphisms at both alpha-globin (Hba, Hbc) and beta-globin (Hbd) loci. Population gene frequencies of beta-globin variants (d0 and d1 haplotypes) are not correlated with altitude, whereas a1 c1 alpha-globin haplotypes are fixed in low-altitude populations, and a0 c0 haplotypes reach near fixation at high altitudes. We examined the effects of alpha- and beta-globin variants on blood oxygen affinity and on aerobic performance, measured as maximum oxygen consumption (VËO2max). Exercise and cold exposure were used to elicit VËO2max. Experiments were performed at low (340 m) and high (3,800 m) altitude to include the range of oxygen partial pressures encountered by wild deer mice. Beta-globin variants had little effect on blood oxygen affinity or VËO2max. Oxygen-dissociation curves from a0 c0 and a1 c1 homozygotes and heterozygotes had similar shapes, but the P50 of a0 c0 homozygotes was significantly lower than that of other genotypes. Mice carrying a1 c1 /a1 c1 genotypes had the highest VËO2max at low altitude, but mice with a0 c0 /a0 c0 genotypes had the highest VËO2max at high altitude. Mice carrying rare recombinant alpha-globin haplotypes (a0 c1 ) had lower VËO2max than nonrecombinant genotypes as a whole but in most cases were not significantly different from nonrecombinant heterozygotes (a0 c0 /a1 c1 ). We conclude that genetic adaptation to different altitudes was important in the evolution of deer mouse alpha-globin polymorphisms and in the maintenance of linkage disequilibrium in the alpha-globin loci but was not a significant factor in the evolution of beta-globin polymorphisms.