Why mammalian lineages respond differently to sexual selection: metabolic rate constrains the evolution of sperm size

The hypothesis that sperm competition should favour increases in sperm size, because it results in faster swimming speeds, has received support from studies on many taxa, but remains contentious for mammals. We suggest that this may be because mammalian lineages respond differently to sexual selection, owing to major differences in body size, which are associated with differences in mass-specific metabolic rate. Recent evidence suggests that cellular metabolic rate also scales with body size, so that small mammals have cells that process energy and resources from the environment at a faster rate. We develop the 'metabolic rate constraint hypothesis' which proposes that low mass-specific metabolic rate among large mammals may limit their ability to respond to sexual selection by increasing sperm size, while this constraint does not exist among small mammals. Here we show that among rodents, which have high mass-specific metabolic rates, sperm size increases under sperm competition, reaching the longest sperm sizes found in eutherian mammals. By contrast, mammalian lineages with large body sizes have small sperm, and while metabolic rate (corrected for body size) influences sperm size, sperm competition levels do not. When all eutherian mammals are analysed jointly, our results suggest that as mass-specific metabolic rate increases, so does maximum sperm size. In addition, species with low mass-specific metabolic rates produce uniformly small sperm, while species with high mass-specific metabolic rates produce a wide range of sperm sizes. These findings support the hypothesis that mass-specific metabolic rates determine the budget available for sperm production: at high levels, sperm size increases in response to sexual selection, while low levels constrain the ability to respond to sexual selection by increasing sperm size. Thus, adaptive and costly traits, such as sperm size, may only evolve under sexual selection when metabolic rate does not constrain cellular budgets.     

Effects of changing ambient temperature on metabolic, heart, and ventilation rates during steady state hibernation in golden-mantled ground squirrels (Spermophilus lateralis)

To determine whether metabolic rate is suppressed in a temperature-independent fashion in the golden-mantled ground squirrel during steady state hibernation, we measured body temperature and metabolic rate in ground squirrels during hibernation at different T(a)'s. In addition, we attempted to determine whether heart rate, ventilation rate, and breathing patterns changed as a function of body temperature or metabolic rate. We found that metabolic rate changed with T(a) as it was raised from 5 degrees to 14 degrees C, which supports the theory that different species sustain falls in metabolic rate during hibernation in different ways. Heart rate and breathing pattern also changed with changing T(a), while breathing frequency did not. That the total breathing frequency did not correlate closely with oxygen consumption or body temperature, while the breathing pattern did, raises important questions regarding the mechanisms controlling ventilation during hibernation.     

芘在土壤中的共代谢降解研究

高分子量多环芳烃（PAHs)的降解通常以共代谢方式进行,研究比较了高分子量多环芳烃代表种类芘作为唯一C源和能源的降解过程和有共代谢底物存在下的降解过程,结果表明,25d后前者中芘的降解率57％,而后者中芘的降解率为80％,且有共代谢底物存在下,芘在降解过程中关衰期缩短;水扬酸,邻苯二甲酸,琥珀酸钠能作为共代谢底物提高芘的降解率,琥珀酸钠效果最好,芘和低要子量多环芳烃之间也有共代谢关系,菲促进了芘的降解,但萘未出现同样的结果,此外,这阐明了共代谢原理和适宜作高分子量多环芳烃共代谢底物的物质。     

Systematizing the generation of missing metabolic knowledge

Genome‐scale metabolic network reconstructions are built from all of the known metabolic reactions and genes in a target organism. However, since our knowledge of any organism is incomplete, these network reconstructions contain gaps. Reactions may be missing, resulting in dead‐ends in pathways, while unknown gene products may catalyze known reactions. New computational methods that analyze data, such as growth phenotypes or gene essentiality, in the context of genome‐scale metabolic networks, have been developed to predict these missing reactions or genes likely to fill these knowledge gaps. A growing number of experimental studies are appearing that address these computational predictions, leading to discovery of new metabolic capabilities in the target organism. Gap‐filling methods can thus be used to improve metabolic network models while simultaneously leading to discovery of new metabolic gene functions. Biotechnol. Bioeng. 2010;107: 403–412. © 2010 Wiley Periodicals, Inc.     

一种基于代谢网络分析最小化基因组的方法及其在大肠杆菌中的应用

最小生命体的合成是合成生物学研究的重要方向。最小化基因组的同时而又不对细胞生长产生影响是代谢工程研究的一个重要目标。文中提出了一种从基因组尺度代谢网络模型出发,通过零通量反应删除及对非必需基因组合删除计算获得基因组最小化代谢网络模型的方法,利用该方法简化了大肠杆菌经典代谢网络模型iAF1260,由起始的1 260个基因简化得到了312个基因,而最优生物质生成速率保持不变。基因组最小化代谢网络模型预测了在细胞正常生长的前提下包含最少基因的代谢途径,为大肠杆菌获得最小基因组的湿实验设计提供了重要参考。     

Energetic inequivalence in eusocial insect colonies

The energetic equivalence rule states that population-level metabolic rate is independent of average body size. This rule has been both supported and refuted by allometric studies of abundance and individual metabolic rate, but no study, to my knowledge, has tested the rule with direct measurements of whole-population metabolic rate. Here, I find a positive scaling of whole-colony metabolic rate with body size for eusocial insects. Individual metabolic rates in these colonies scaled with body size more steeply than expected from laboratory studies on insects, while population size was independent of body size. Using consumer-resource models, I suggest that the colony-level metabolic rate scaling observed here may arise from a change in the scaling of individual metabolic rate resulting from a change in the body size dependence of mortality rates.     

Effects of aging and arm swing on the metabolic cost of stability in human walking

To gain insight into the mechanical determinants of walking energetics, we investigated the effects of aging and arm swing on the metabolic cost of stabilization. We tested two hypotheses: (1) elderly adults consume more metabolic energy during walking than young adults because they consume more metabolic energy for lateral stabilization, and (2) arm swing reduces the metabolic cost of stabilization during walking in young and elderly adults. To test these hypotheses, we provided external lateral stabilization by applying bilateral forces (10% body weight) to a waist belt via elastic cords while young and elderly subjects walked at 1.3m/s on a motorized treadmill with arm swing and with no arm swing. We found that the external stabilizer reduced the net rate of metabolic energy consumption to a similar extent in elderly and young subjects. This reduction was greater (6-7%) when subjects walked with no arm swing than when they walked normally (3-4%). When young or elderly subjects eliminated arm swing while walking with no external stabilization, net metabolic power increased by 5-6%. We conclude that the greater metabolic cost of walking in elderly adults is not caused by a greater cost of lateral stabilization. Moreover, arm swing reduces the metabolic cost of walking in both young and elderly adults likely by contributing to stability.     

恒温脊椎动物最大持续能量代谢率及其研究进展

研究最大持续代谢率具有重要的理论和实践意义,本文概述了近年来国外对脊椎动物最大持续代谢率研究的成果,概括介绍了限制最大持续代谢率的四个假说：（1）食物限制假说（food limit hypothesis) ,(2)外周限制假说（peripheral limit hypotheisis),(3)中心限制假说（central limit hypothesis)和（4）对称性形态构成假说（symmorphosis hypothesis),分析了静止代谢率随持续代谢率的增加而增加的机理,讨论了最大持续代谢率对动物的生态进化意义,最后指出了最大持续代谢率研究中可能的发展前景。     

Metabolomics analysis reveals differences in evolution between maize and rice

Metabolites are the intermediate and final products of metabolism, which play essential roles in plant growth, evolution and adaptation to changing climates. However, it is unclear how evolution contributes to metabolic variation in plants. Here, we investigated the metabolomics data from leaf and seed tissues in maize and rice. Using principal components analysis based on leaf metabolites but not seed metabolites, metabolomics data could be clearly separated for rice Indica and Japonica accessions, while two maize subgroups, temperate and tropical, showed more visible admixture. Rice and maize seed exhibited significant interspecific differences in metabolic variation, while within rice, leaf and seed displayed similar metabolic variations. Among 10 metabolic categories, flavonoids had higher variation in maize than rice, indicating flavonoids are a key constituent of interspecific metabolic divergence. Interestingly, metabolic regulation was also found to be reshaped dramatically from positive to negative correlations, indicative of the differential evolutionary processes in maize and rice. Moreover, perhaps due to this divergence significantly more metabolic interactions were identified in rice than maize. Furthermore, in rice, the leaf was found to harbor much more intense metabolic interactions than the seed. Our result suggests that metabolomes are valuable for tracking evolutionary history, thereby complementing and extending genomic insights concerning which features are responsible for interspecific differentiation in maize and rice.     

Systematic identification and elimination of flux bottlenecks in the aldehyde production pathway of Synechococcus elongatus PCC 7942

Isotopically nonstationary metabolic flux analysis (INST-MFA) provides a versatile platform to quantitatively assess in vivo metabolic activities of autotrophic systems. By applying INST-MFA to recombinant aldehyde-producing cyanobacteria, we identified metabolic alterations that correlated with increased strain performance in order to guide rational metabolic engineering. We identified four reactions adjacent to the pyruvate node that varied significantly with increasing aldehyde production: pyruvate kinase (PK) and acetolactate synthase (ALS) fluxes were directly correlated with product formation, while pyruvate dehydrogenase (PDH) and phosphoenolpyruvate carboxylase (PPC) fluxes were inversely correlated. Overexpression of enzymes for PK or ALS did not result in further improvements to the previous best-performing strain, while downregulation of PDH expression (through antisense RNA expression) or PPC flux (through expression of the reverse reaction, phosphoenolpyruvate carboxykinase) provided significant improvements. These results illustrate the potential of INST-MFA to enable a systematic approach for iterative identification and removal of pathway bottlenecks in autotrophic host cells.     

Role of the melanocortin-4 receptor in metabolic rate and food intake in mice

We evaluated the role of the melanocortin-4 receptor (MC-4R) in the control of metabolic rate and food intake in mice. Intraperitoneal administration of the non-selective MC-R agonist melanotan II (MT-II; a cyclic heptapeptide) increases metabolic rate in wildtype mice, while MC-4R knockout mice are insensitive to the effects of MT-II on metabolic rate. MC-4R knockout mice are also insensitive to the effects of MT-II on reducing food intake. We conclude that MC-4R can mediate control of both metabolic rate and food intake in mice. We infer that a role for MC-3R in mediating the acute effects of MT-II on basal metabolic rate and food intake in wildtype mice seems limited.     

Resting metabolic rate can vary with age independently from body mass changes in the Colorado potato beetle, Leptinotarsa decemlineata

Temperature and mass dependency of insect metabolic rates are well known, while less attention has been given to other factors, such as age. Among insect species that experience seasonal variation in environmental conditions, such as in temperate latitudes, age may also have indirect effects on the metabolic rate. We examined the effect of age on the resting metabolic rate of Leptinotarsa decemlineata during 11 days after adult emergence by using flow-through respirometry. Age had a significant mass-independent effect on metabolic rate of beetles. A twofold increase in metabolic rate occurred during the first 2 days of adult life after which metabolic rate decreased with age relatively slowly. Ten day-old adult beetles had a metabolic rate similar to newly emerged beetles. The beetles have to be able to complete their development and prepare for overwintering during the relatively short favourable summer periods. Therefore, the observed pattern in metabolic rate may reflect physiological changes in the pre-diapause beetles adapted to temperate latitudes.     

Metabolic responses to gradual cooling in chicken eggs treated with thiourea and oxygen

1. Late prenatal chicken embryos in eggs injected with saline showed a feeble homeothermic metabolic response to gradual cooling. This response was absent in thiourea-treated eggs. This suggests that the incipient homeothermic metabolic response before paranatal life may be attributed to thyroid development. 2. The compensatory metabolic response disappeared in embryos exposed to a hypoxic environment, while it was augmented in eggs in pure O2, decreasing as ambient temperature fell. 3. These results may indicate that the homeothermic metabolic response in late embryos is O2-conductance-limited and power-limited as previously suggested.     

Yeast metabolic innovations emerged via expanded metabolic network and gene positive selection

Yeasts are known to have versatile metabolic traits, while how these metabolic traits have evolved has not been elucidated systematically. We performed integrative evolution analysis to investigate how genomic evolution determines trait generation by reconstructing genome‐scale metabolic models (GEMs) for 332 yeasts. These GEMs could comprehensively characterize trait diversity and predict enzyme functionality, thereby signifying that sequence‐level evolution has shaped reaction networks towards new metabolic functions. Strikingly, using GEMs, we can mechanistically map different evolutionary events, e.g. horizontal gene transfer and gene duplication, onto relevant subpathways to explain metabolic plasticity. This demonstrates that gene family expansion and enzyme promiscuity are prominent mechanisms for metabolic trait gains, while GEM simulations reveal that additional factors, such as gene loss from distant pathways, contribute to trait losses. Furthermore, our analysis could pinpoint to specific genes and pathways that have been under positive selection and relevant for the formulation of complex metabolic traits, i.e. thermotolerance and the Crabtree effect. Our findings illustrate how multidimensional evolution in both metabolic network structure and individual enzymes drives phenotypic variations.     

Microsomal formation and chemical decomposition of pargyline N-oxide

Pargyline undergoes metabolic N-oxidation in rat and rabbit liver microsomal preparations. The reaction requires oxygen and is NADPH dependent. N-oxidation and N-demethylation are equal in both control and induced rat liver microsomes, while N-oxidation is more dominant in rabbit tissue. Experiments investigating the CO-sensitivity and the effects of metyrapone suggest that cytochrome P-450 systems are involved in both reactions in the rat while an additional enzyme is responsible for the N-oxidation in the rabbit. Pargyline N-oxide is characterized by chemical instability and undergoes two consecutive rearrangements to yield propenal and Schiff bases, the latter undergoing hydrolysis to aldehydes and primary amines. Accordingly, due to the inherent instability of the N-oxide, metabolic N-oxidation of pargyline is, in addition to α-carbon oxidation, indicated as a metabolic route to benzaldehyde. Similarly the ease with which pargyline N-oxide generates propenal implicates N-oxidation as a metabolic route to be considered when evaluating the toxicity of pargyline.     

Stem metabolism: Insights from oncometabolism and vice versa

Metabolism, is a transversal hot research topic in different areas, resulting in the integration of cellular needs with external cues, involving a highly coordinated set of activities in which nutrients are converted into building blocks for macromolecules, energy currencies and biomass. Importantly, cells can adjust different metabolic pathways defining its cellular identity. Both cancer cell and embryonic stem cells share the common hallmark of high proliferative ability but while the first represent a huge social-economic burden the second symbolize a huge promise. Importantly, research on both fields points out that stem cells share common metabolic strategies with cancer cells to maintain their identity as well as proliferative capability and, vice versa cancer cells also share common strategies regarding pluripotent markers. Moreover, the Warburg effect can be found in highly proliferative non-cancer stem cells as well as in embryonic stem cells that are primed towards differentiation, while a bivalent metabolism is characteristic of embryonic stem cells that are in a true naïve pluripotent state and cancer stem cells can also range from glycolysis to oxidative phosphorylation. Therefore, this review aims to highlight major metabolic similarities between cancer cells and embryonic stem cells demonstrating that they have similar strategies in both signaling pathways regulation as well as metabolic profiles while focusing on key metabolites.     

Evolutionary models of metabolism, behaviour and personality

I explore the relationship between metabolism and personality by establishing how selection acts on metabolic rate and risk-taking in the context of a trade-off between energy and predation. Using a simple time budget model, I show that a high resting metabolic rate is not necessarily associated with a high daily energy expenditure. The metabolic rate that minimizes the time spent foraging does not maximize the net gain rate while foraging, and it is not always advantageous for animals to have a higher metabolic rate when food availability is high. A model based on minimizing the ratio of mortality rate to net gain rate is used to determine how a willingness to take risks should be correlated with metabolic rate. My results establish that it is not always advantageous for animals to take greater risks when metabolic rate is high. When foraging intensity and metabolic rate coevolve, I show that in a particular case different combinations of foraging intensity and metabolic rate can have equal fitness.     

Colonization and recovery of lotic epilithic communities: A metabolic approach

Community respiration and net primary productivity measurements from precleaned and disturbed substrates of various sizes were collected to examine the colonization and recovery rates of lotic epilithic communities in situ. The assumptions and limitations of the technique for monitoring metabolic recovery are discussed. The results indicate that substrate size and heterogeneity affect the rates of metabolic recovery; metabolic recovery of the heterotrophic community component generally occurs before the autotrophic; following a physical disturbance 13–21 days are required for metabolic recovery while pre-cleaned mixed and homogenous large sized substrates require 15–21 days; a temporary summer metabolic equilibrium appears to exist in the Sheep River, the duration of which is dependent on abiotic environmental variables. Future metabolic studies should include structure and composition measurements to attain maximum information on the recovery of epilithic communities.     

Targeting amino acid metabolism in cancer growth and anti-tumor immune response

Recent advances in amino acid metabolism have revealed that targeting amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. There are currently several drugs in clinical trials that specifically target amino acid metabolic pathways in tumor cells. In the context of the tumor microenvironment,however,tumor cells form metabolic relationships with immune cells,and they oftencompete for common nutrients. Many tumors evolved to escape immune surveillance by taking advantage of their metabolic flexibility and redirecting nutrients for their own advantage. This review outlines the most recent advances in targeting amino acid metabolic pathways in cancer therapy while giving consideration to the impact these pathways may have on the anti-tumor immune response.     

Preferred step frequency during downhill running may be determined by muscle activity

It is well established that metabolic cost is minimized at an individual’s running preferred step frequency (PSF). It has been proposed that the metabolic minimum at PSF is due to a tradeoff between mechanical factors, however, this ignores muscle activity, the primary consumer of energy. Thus, we hypothesized that during downhill running, total muscle activity would be greater with deviations from PSF. Specifically, we predicted that slow step frequencies would have greater stance activity while fast step frequencies would have greater swing activity. We collected metabolic cost and leg muscle activity data while 10 healthy young adults ran at 3.0 m/s for 5 min at level and downhill at PSF and ±15% PSF. In support of our hypothesis, there was a significant main effect for step frequency for both metabolic cost and total muscle activity. In addition, there was greater muscle activity in the stance phase during the slower step frequency while muscle activity was greater in the swing phase during the fast step frequency. This suggests that PSF is partially determined by the tradeoff between the greater cost of muscle activity in the swing phase and lower cost in the stance phase with faster step frequency.