The quantitative genetics of maximal and basal rates of oxygen consumption in mice

A positive genetic correlation between basal metabolic rate (BMR) and maximal (VO(2)max) rate of oxygen consumption is a key assumption of the aerobic capacity model for the evolution of endothermy. We estimated the genetic (V(A), additive, and V(D), dominance), prenatal (V(N)), and postnatal common environmental (V(C)) contributions to individual differences in metabolic rates and body mass for a genetically heterogeneous laboratory strain of house mice (Mus domesticus). Our breeding design did not allow the simultaneous estimation of V(D) and V(N). Regardless of whether V(D) or V(N) was assumed, estimates of V(A) were negative under the full models. Hence, we fitted reduced models (e.g., V(A) + V(N) + V(E) or V(A) + V(E)) and obtained new variance estimates. For reduced models, narrow-sense heritability (h(2)(N)) for BMR was <0.1, but estimates of h(2)(N) for VO(2)max were higher. When estimated with the V(A) + V(E) model, the additive genetic covariance between VO(2)max and BMR was positive and statistically different from zero. This result offers tentative support for the aerobic capacity model for the evolution of vertebrate energetics. However, constraints imposed on the genetic model may cause our estimates of additive variance and covariance to be biased, so our results should be interpreted with caution and tested via selection experiments.     

Anatomic and molecular correlates of divergent selection for basal metabolic rate in laboratory mice

Proximal mechanisms describing the evolution of high levels of basal metabolic rate (BMR) in endotherms are one of the most intriguing problems of evolutionary physiology. Because BMR mostly reflects metabolic activity of internal organs, evolutionary increase in BMR could have been realized by an increase in relative organ size and/or mass-specific cellular metabolic rate. According to the "membrane pacemaker" theory of metabolism, the latter is mediated by an increase in the average number of double bonds (unsaturation index) in cell membrane fatty acids. To test this, we investigated the effect of divergent artificial selection for body-mass-corrected BMR on the mass of internal organs and the fatty acid composition of cell membranes in laboratory mice (Mus musculus). Mice from the high-BMR line had considerably larger liver, kidneys, heart, and intestines. In contrast, the unsaturation index of liver cell membranes was significantly higher in low-BMR mice, mainly because of the significantly higher content of highly polyunsaturated 22 : 6 docosahexanoic fatty acid. Thus, divergent selection for BMR did not affect fatty acyl composition of liver and kidney phospholipids in the direction predicted by the membrane pacemaker theory. We conclude that an intraspecific increase in BMR may rapidly evolve mainly as a result of the changes in size of internal organs, without simultaneous increase of the unsaturation index in cell membrane lipids.     

EVOLUTION OF BASAL METABOLIC RATE AND ORGAN MASSES IN LABORATORY MICE

Animal species of similar body mass vary widely in basal metabolic rate (BMR). A central problem of evolutionary physiology concerns the anatomical/physiological origin and functional significance of that variation. It has been hypothesized that such interspecific differences in wild animals evolved adaptively from differences in relative sizes of metabolically active organs. In order to minimize confounding phenotypic effects and maximize relevant genetic variation, we tested for intraspecific correlations between body-mass-corrected BMR and masses of four organs (heart, kidney, liver, and small intestine) among six inbred strains of mice. We found significant differences between strains in BMR and in masses of all four organs. Strains with exceptionally high (or low) BMR tended to have disproportionately large (or small) organs. The mass of each organ was correlated with the masses of each of the other three organs. Variation in organ masses accounted for 52% of the observed variation in BMR, of which 42% represented between-strain variation, and 10% represented within-strain variation. This conclusion is supported by published measurements of metabolic rates of tissue slices from the four organs. The correlation between BMR and intestine or heart mass arose exclusively from differences between strains, while the correlation between BMR and liver or kidney mass also appeared in comparing individual mice within the same strain. Thus, even though the masses of the four examined organs account for no more than 17% of total body mass, their high metabolic activities or correlated factors account for much of the variation in BMR among mice. We suggest that large masses of metabolically active organs are subject to natural selection through evolutionary trade-offs. On the one hand, they make possible high-energy budgets (advantageous under some conditions), but on the other hand they are energetically expensive to maintain.     

Variation of loci encoding homologous enzymes in an evolutionary series of vertebrates

A study of variability of 11 allozyme loci (sAat, G3pdh, Gpi, sIdh, Ldh-A, Ldh-B, sMdh, sMe, sSod, Pgdh, and Sdh) in the evolutionary series of vertebrates from Cyclostomat to Mammalia revealed that (1) in vertebrates, these loci encoding multimeric enzymes are characterized by different heterozygosity levels, the extremes of which (represented by loci Ldh-A and Pgdh) differ from each other more than by a factor of 4; (2) classes of vertebrates markedly differed from one another in genetic variation; lower Tetrapoda are characterized by the highest level of genetic polymorphism, the classes representing the margins of the phyletic line-primitive (Cyclostomata and Chondrchthyes) and advanced (Aves and Mammalia)--have minimum heterozygosity levels, whereas Osteichthyes are characterized by intermediate heterozygosity level; (3) in the evolutionary series of vertebrates, heterozygosity varies rather independently in the groups of loci characterized by low, medium, and high variability. These patterns are explained in the context of intraorganismic factors: integration of mono- and polygenic traits (primarily, body size and ontogeny rate) and evolutionary specialization.     

长爪沙鼠的代谢率与器官的关系

我们测定了野生长爪沙鼠（Meriones unguiculatus)的基础代谢率和冷诱导的最大代谢率,分析了动物体内11种器官或组织的大小与代谢率的关系。长爪沙鼠的基础代谢率为118.10mlO2/h,最大代谢率为659.83mlO2/h。经过残差分析表明,基础代谢率并不与任何一种器官或组织相关,而最大代谢率与小肠湿重（n=20,r=-0.478,P=0.033)和消化道全长（n=20,r=-0.487,P=0.030)显著相关,表明体内器官重量的差别并不是造成种内基础代谢率差别的原因;体内存在着与最大代谢率相关的“代谢机器”,消化系统（特别是小肠）是这一代谢机器的重要组成部分,但代谢机器的大小并不能通过基础代谢率反映出来。基础代谢率与最大代谢率不相关,因此不支持“较高的基础代谢率能够产生较高的非基础代谢率（最大代谢率等）”的假设。     

Anatomic and energetic correlates of divergent selection for basal metabolic rate in laboratory mice

The aerobic capacity model postulates that high basal metabolic rates (BMR) associated with endothermy evolved as a correlated response to the selection on maximum, peak metabolic rate Vo2max. Furthermore, the model assumes that BMR and Vo2max are causally linked, and therefore, evolutionary changes in their levels cannot occur independently. To test this, we compared metabolic and anatomical correlates of selection for high and low body mass-corrected BMR in males of laboratory mice of F18 and F19 selected generations. Divergent selection resulted in between-line difference in BMR equivalent to 2.3 phenotypic standard deviation units. Vo2max elicited by forced swimming in 20 degrees C water was higher in the low BMR than high BMR line and did not differ between the lines when elicited by exposure to heliox at -2.5 degrees C. Moreover, the magnitude of swim- and heliox-induced hypothermia was significantly smaller in low BMR mice, whereas their interscapular brown adipose tissue was larger than in high BMR mice. Our results are therefore at variance with the predictions of aerobic capacity model. The selection also resulted in correlated response in food consumption (C) and masses of metabolically active internal organs: kidneys, liver, small intestine, and heart, which fuel maximum, sustained metabolic rate (SusMR) rather than Vo2max. These correlated responses were strong enough to claim the existence of positive, genetic correlations between BMR and the mass of viscera as well as C. Thus, our findings support the suggestion that BMR evolved as a correlated response to selection for SusMR, not Vo2max. In functional terms BMR should therefore be interpreted as a measure of energetic costs of maintenance of metabolic machinery necessary to sustain high levels of energy assimilation rate.     

Changes in body temperature influence the scaling of VO2max and aerobic scope in mammals

Debate on the mechanism(s) responsible for the scaling of metabolic rate with body size in mammals has focused on why the maximum metabolic rate (VO2max ) appears to scale more steeply with body size than the basal metabolic rate (BMR). Consequently, metabolic scope, defined as VO2max/BMR, systematically increases with body size. These observations have led some to suggest that VO2max, and BMR are controlled by fundamentally different processes, and to discount the generality of models that predict a single power-law scaling exponent for the size dependence of the metabolic rate. We present a model that predicts a steeper size dependence for VO2max than BMR based on the observation that changes in muscle temperature from rest to maximal activity are greater in larger mammals. Empirical data support the model's prediction. This model thus provides a potential theoretical and mechanistic link between BMR and VO2 max.     

Spatial variation in the evolutionary potential and constraints of basal metabolic rate and body mass in a wild bird

An organism's energy budget is strongly related to resource consumption, performance, and fitness. Hence, understanding the evolution of key energetic traits, such as basal metabolic rate (BMR), in natural populations is central for understanding life-history evolution and ecological processes. Here we used quantitative genetic analyses to study evolutionary potential of BMR in two insular populations of the house sparrow (Passer domesticus). We obtained measurements of BMR and body mass (M_b) from 911 house sparrows on the islands of Leka and Vega along the coast of Norway. These two populations were the source populations for translocations to create an additional third, admixed ‘common garden’ population in 2012. With the use of a novel genetic group animal model concomitant with a genetically determined pedigree, we differentiate genetic and environmental sources of variation, thereby providing insight into the effects of spatial population structure on evolutionary potential. We found that the evolutionary potential of BMR was similar in the two source populations, whereas the Vega population had a somewhat higher evolutionary potential of M_b than the Leka population. BMR was genetically correlated with M_b in both populations, and the conditional evolutionary potential of BMR (independent of body mass) was 41% (Leka) and 53% (Vega) lower than unconditional estimates. Overall, our results show that there is potential for BMR to evolve independently of M_b, but that selection on BMR and/or M_b may have different evolutionary consequences in different populations of the same species.     

Variation of Loci Encoding Homologous Enzymes in the Evolutionary Series of Vertebrates

A study of variability of 11 allozyme loci (sAat, G3pdh, Gpi, sIdh, Ldh-A, Ldh-B, sMdh, sMe, sSod, Pgdh, and Sdh) in the evolutionary series of vertebrates from Cyclostomat to Mammalia revealed that (1) in vertebrates, these loci encoding multimeric enzymes are characterized by different heterozygosity levels, the extremes of which (represented by loci Ldh-A and Pgdh) differ from each other more than by a factor of 4; (2) classes of vertebrates markedly differed from one another in genetic variation; lower Tetrapoda are characterized by the highest level of genetic polymorphism, the classes representing the margins of the phyletic line—primitive (Cyclostomata and Chondrchthyes) and advanced (Aves and Mammalia)—have minimum heterozygosity levels, whereas Osteichthyes are characterized by intermediate heterozygosity level; (3) in the evolutionary series of vertebrates, heterozygosity varies rather independently in the groups of loci characterized by low, medium, and high variability. These patterns are explained in the context of intraorganismic factors: integration of mono- and polygenic traits (primarily, body size and ontogeny rate) and evolutionary specialization.     

Quantitative genetics and fitness effects of basal metabolism

The physiological requirements of reproduction are predicted to generate a link between energy, physiology and life history traits. Simultaneously, low maintenance costs, measured by energy consumption, are expected to be advantageous. Here we investigated fitness relatedness of traits by estimating genetic correlations between, and inbreeding depression for, body mass, basal metabolic rate (BMR) and other life history characters in a wild rodent, Myodes glareolus. The narrow-sense heritability of absolute and mass corrected BMRs were high for females (h² = 0.48 and 0.42) but low and non-significant for males (0.32 and 0.09). A significant positive genetic correlation between BMR and litter size suggests that traits connected to female fecundity might favour higher metabolism (i.e. support increased intake hypothesis). However, the estimates of inbreeding depression indicate that, while higher values of body mass and female litter size could be positively associated with overall fitness, the association between BMR and overall fitness in bank voles would be negative (i.e. support compensation hypothesis). This result suggests that the advantages of larger litters and larger body mass might be evolutionary constrained by high costs of maintenance of those traits, as reflected by the level of basal metabolism.     

The mode of evolution of molecular markers in populations of house mice under artificial selection for locomotor behavior

A complete understanding of the mode of evolution of molecular markers is important for making inferences about different population genetic parameters, especially because a number of studies have reported patterns of allelic variation at molecular markers that are not in agreement with neutral evolutionary expectations. In the present study, house mice (Mus domesticus) from the fourteenth generation of a selection experiment for increased voluntary wheel-running activity were used to test how selection on a complex behavior affects the distribution of allelic variation by examining patterns of variation at six microsatellite and four allozyme loci. This population had a hierarchical structure that allowed for simultaneous testing of the effects of selection and genetic drift on the distribution of allelic variation by comparing observed patterns of allele frequencies and estimates of genetic divergence at multiple hierarchical levels to expectations under models of neutral evolution. The levels of genetic divergence among replicate lines and between selection groups, estimated from microsatellite data or pooled microsatellite and allozyme data, were not significantly different from expectations under neutral evolution. Furthermore, the pattern of change of allele frequencies between the base population and generation 14 was largely in agreement with expectations under neutral evolution (although the PGM locus exhibited a pattern of change within populations that was difficult to explain under neutral evolution). Overall the results generally provide support for the neutral evolution of molecular markers.     

Nucleotide variation in wild and inbred mice

The house mouse is a well-established model organism, particularly for studying the genetics of complex traits. However, most studies of mice use classical inbred strains, whose genomes derive from multiple species. Relatively little is known about the distribution of genetic variation among these species or how variation among strains relates to variation in the wild. We sequenced intronic regions of five X-linked loci in large samples of wild Mus domesticus and M. musculus, and we found low levels of nucleotide diversity in both species. We compared these data to published data from short portions of six X-linked and 18 autosomal loci in wild mice. We estimate that M. domesticus and M. musculus diverged <500,000 years ago. Consistent with this recent divergence, some gene genealogies were reciprocally monophyletic between these species, while others were paraphyletic or polyphyletic. In general, the X chromosome was more differentiated than the autosomes. We resequenced classical inbred strains for all 29 loci and found that inbred strains contain only a small amount of the genetic variation seen in wild mice. Notably, the X chromosome contains proportionately less variation among inbred strains than do the autosomes. Moreover, variation among inbred strains derives from differences between species as well as from differences within species, and these proportions differ in different genomic regions. Wild mice thus provide a reservoir of additional genetic variation that may be useful for mapping studies. Together these results suggest that wild mice will be a valuable complement to laboratory strains for studying the genetics of complex traits.     

Broad‐scale ecological implications of ectothermy and endothermy in changing environments

Aim Physiology is emerging as a basis for understanding the distribution and diversity of organisms, and ultimately for predicting their responses to climate change. Here we review how the difference in physiology of terrestrial vertebrate ectotherms (amphibians and reptiles) and endotherms (birds and mammals) is expected to influence broad‐scale ecological patterns. Location Global terrestrial ecosystems. Methods We use data from the literature and modelling to analyse geographic gradients in energy use and thermal limits. We then compare broad‐scale ecological patterns for both groups with expectations stemming from these geographic gradients. Results The differences in thermal physiology between ectotherms and endotherms result in geographically disparate macrophysiological constraints. Field metabolic rate (FMR) is stable or decreases slightly with temperature for endotherms, while it generally increases for ectotherms, leading to opposing latitudinal gradients of expected FMR. Potential activity time is a greater constraint on the distributions of ectotherms than endotherms, particularly at high latitudes. Differences in the primary correlates of abundance and species richness for two representative taxonomic groups are consistent with the consequences of these basic physiological differences. Ectotherm richness is better predicted by temperature, whereas endotherm richness is more strongly associated with primary productivity. Finally, in contrast to endotherms, ectotherm richness is not strongly related to abundance. Main conclusions Differences in thermal physiology affect how organisms interact with and are constrained by their environment, and may ultimately explain differences in the geographic pattern of biodiversity for endotherms and ectotherms. Linking the fields of physiological and broad‐scale ecology should yield a more mechanistic understanding of how biodiversity will respond to environmental change.     

RAPD- and allozyme analysis of genetic variability of Panax ginseng C.A. Meyer and P. quinquefolius L

Inter- and intraspecific variation of two ginseng species Panax ginseng and P. quinquefolius was estimated by studying 159 RAPD and 39 allozyme loci. Parameters of polymorphism and genetic diversity were determined and a tree was constructed to characterize the differences between individual plants, samples, and species. Genetic variation in P. ginseng proved to be lower than in P. quinquefolius. Gene diversity in the total P. ginseng sample was comparable with the mean expected heterozygosity of herbaceous plants. This suggests that wild P. ginseng plants in various areas of the currently fragmented natural habitat and cultivated plants of different origin have retained a significant proportion of their gene pool. The mean heterozygosity calculated per polymorphic locus for the RAPD phenotypes is similar to that of the allozyme loci and may be helpful in estimating gene diversity in populations of rare and endangered plant species.     

DEVELOPMENTAL NOISE,PHENOTYPIC PLASTICITY,AND ALLOZYME HETEROZYGOSITY IN DAPHNIA

Previous theories and studies have postulated negative correlations between allozyme heterozygosity and developmental noise and between heterozygosity and phenotypic plasticity. We examined these relationships for morphological and life-history traits of Daphnia magna in four independent experiments using two different Moscow populations and one German population. Clones were raised under a range of food levels or individual densities. Heterozygosity was scored at five allozyme loci in two experiments and at three loci in two others. Relative differences in developmental noise among clones with different heterozygosity levels were estimated as the pooled residual variation from an analysis of variation that removed the effects of macroenvironment, clones, and their interaction. Plasticity was measured as the amount of macroenvironmental variation plus genotype-by-environment interaction variation. We found a positive correlation between developmental noise and heterozygosity, although this correlation varied among traits and experiments. This result contradicts most previous claims about these relationships. In contrast, we found that phenotypic plasticity and heterozygosity were negatively correlated for some traits. Developmental noise and phenotypic plasticity were correlated for only two traits in two different experiments. This trait-specific relationship is in concordance with previous studies. Our results could not be explained by effects of developmental time, a previously hypothesized mechanism. We propose several explanations for our results and the disparate results of others that do not require that heterozygosity be the actual cause of variation in developmental noise.     

Population Genetic Structure of Endemic and Endangered Yellow Catfish, Horabagrus brachysoma, Using Allozyme Markers

The allozyme variation and population genetic structure of Horabagrus brachysoma in three natural populations from the southern part of the Western Ghats region, India, were investigated by polyacrylamide gel electrophoresis. Variations at 14 loci from 14 enzyme systems were analyzed. The allozyme analysis revealed a high level of genetic variation in this species, with an average of observed alleles per locus of 2.357 and observed heterozygosity of 0.178. The positive value of the fixation index (FIS=0.507) implied a significant deficiency of heterozygosity at the population level. The highly significant probability (P<0.0001) for the overall loci suggested that the three sample sets were not part of the same gene pool.     

Allozyme and RFLP Heterozygosities as Correlates of Growth Rate in the Scallop Placopecten Magellanicus: A Test of the Associative Overdominance Hypothesis

Several studies have reported positive correlations between the degree of enzyme heterozygosity and fitness-related traits. Notable among these are the correlations between heterozygosity and growth rate in marine bivalves. Whether the correlation is the result of intrinsic functional differences between enzyme variants at the electrophoretic loci scored or arises from non-random genotypic associations between these loci and others segregating for deleterious recessive genes (the associative overdominance hypothesis) is a matter of continuing debate. A prediction of the associative overdominance hypothesis, not shared by explanations that treat the enzyme loci as causative agents of the correlation, is that the correlation is not specific to the type of genetic marker used. We have tested this prediction by scoring heterozygosity at single locus nuclear restriction fragment length polymorphisms (RFLPs) in a cohort of juvenile scallops (Placopecten magellanicus) in which growth rate was known to be positively correlated with an individual's degree of allozyme heterozygosity. A total of 222 individuals were scored for their genotypes at seven allozyme loci, two nonspecific protein loci of unknown function and eight nuclear RFLPs detected by anonymous cDNA probes. In contrast to the enzyme loci, no correlation was observed between growth rate and the degree of heterozygosity at the DNA markers. Furthermore, there was no relationship between the magnitude of heterozygote deficiency at a locus and its effect on the correlation. The differences observed between the effects of allozyme and RFLP heterozygosity on growth rate provide evidence against the associative overdominance hypothesis, but a strong case against this explanation must await corroboration from similar studies in different species.     

Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure

The FTO gene has significant polymorphic variation associated with obesity, but its function is unknown. We screened a population of 150 whites (103F/47M) resident in NE Scotland, United Kingdom, for variants of the FTO gene and linked these to phenotypic variation in their energy expenditure (basal metabolic rate (BMR) and maximal oxygen consumption VO(2)max) and energy intake. There was no significant association between the FTO genotype and BMR or VO(2)max. The FTO genotype was significantly associated (P = 0.024) with variation in energy intake, with average daily intake being 9.0 MJ for the wild-type TT genotype and 10.2 and 9.5 MJ for the "at risk" AT and AA genotypes, respectively. Adjusting intake for BMR did not remove the significance (P = 0.043). FTO genotype probably affects obesity via effects on food intake rather than energy expenditure.     

Comparative losses of quantitative and molecular genetic variation in finite populations of Drosophila melanogaster

Quantitative genetic variation, the main determinant of the ability to evolve, is expected to be lost in small populations, but there are limited data on the effect, and controversy as to whether it is similar to that for near neutral molecular variation. Genetic variation for abdominal and sternopleural bristle numbers and allozyme heterozygosity were estimated in 23 populations of Drosophila melanogaster maintained at effective population sizes of 25, 50, 100, 250 or 500 for 50 generations, as well as in 19 highly inbred populations and the wild outbred base population. Highly significant negative regressions of proportion of initial genetic variation retained on inbreeding due to finite population size were observed for both quantitative characters (b = -0.67 +/- 0.14 and -0.58 +/- 0.11) and allozyme heterozygosity (b = -0.79 +/- 0.10), and the regression coefficients did not differ significantly. Thus, quantitative genetic variation is being lost at a similar rate to molecular genetic variation. However, genetic variation for all traits was lost at rates significantly slower than predicted by neutral theory, most likely due to associative overdominance. Positive, but relatively low correlations were found among the different measures of genetic variation, but their low magnitudes were attributed to large sampling errors, rather than differences in the underlying processes of loss.     

Genetic variation in a subtropical population of Daphnia

We assayed a subtropical population of Daphnia ambigua for genetic variation using protein electrophoresis (9 loci) and quantitative genetics approaches (life history characters). Our goal was to obtain information about relative levels of variation in a subtropical population, and compare them with extensive previous studies in the temperate and arctic zones. The observed level of allozymic variation (H = 0.11) was consistent with those previously observed in other temperate zone Daphnia populations. However, variation for quantitative traits (heritability) was lower than typically observed in previously-studied temperate populations: estimates were not statistically different from zero. Because allozyme heterozygosity was consistent with previous temperate zone estimates, and the polymorphic allozyme loci did not depart from the expectations of Hardy-Weinberg equilibrium, we concluded that a period of clonal selection was the most likely explanation for the low heritabilities observed. We do not conclude that this study provides evidence to suggest that subtropical populations harbor lower levels of genetic variation because of their location.