We have used selective breeding with house mice to study coadaptation of morphology and physiology with the evolution of high daily levels of voluntary exercise. Here, we compared hindlimb bones and muscle masses from the 11th generation of four replicate High Runner (HR) lines of house mice bred for high levels of voluntary wheel running with four non‐selected control (C) lines. Mass, length, diameter, and depth of the femur, tibia‐fibula, and metatarsal bones, as well as masses of gastrocnemius and quadriceps muscles, were compared by analysis of covariance with body mass or body length as the covariate. Mice from HR lines had relatively wider distal femora and deeper proximal tibiae, suggesting larger knee surface areas, and larger femoral heads. Sex differences in bone dimensions were also evident, with males having thicker and shorter hindlimb bones when compared with females. Several interactions between sex, linetype, and/or body mass were observed, and analyses split by sex revealed several cases of sex‐specific responses to selection. A subset of the HR mice in two of the four HR lines expressed the mini‐muscle phenotype, characterized mainly by an ∼50% reduction in hindlimb muscle mass, caused by a Mendelian recessive mutation, and known to have been under positive selection in the HR lines. Mini‐muscle individuals had elongated distal elements, lighter and thinner hindlimb bones, altered 3rd trochanter muscle insertion positions, and thicker tibia‐fibula distal widths. Finally, several differences in levels of directional or fluctuating asymmetry in bone dimensions were observed between HR and C, mini‐ and normal‐muscled mice, and the sexes. This study demonstrates that skeletal dimensions and muscle masses can evolve rapidly in response to directional selection on locomotor behavior.
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Selective breeding for high voluntary exercise in mice increases maximal ( V̇ O2,max) but not basal metabolic rate
In general, sustained high rates of physical activity require a high maximal aerobic capacity (V̇O2,max), which may also necessitate a high basal aerobic metabolism (BMR), given that the two metabolic states are linked via shared organ systems, cellular properties and metabolic pathways. We tested the hypotheses that (a) selective breeding for high voluntary exercise in mice would elevate both V̇O2,max and BMR, and (b) these increases are accompanied by increases in the size of some internal organs (ventricle, triceps surae muscle, liver, kidney, spleen, lung, brain). We measured 72 females from generations 88 and 96 of an ongoing artificial selection experiment comprising four replicate High Runner (HR) lines bred for voluntary daily wheel-running distance and four non-selected control lines. With body mass as a covariate, HR lines as a group had significantly higher V̇O2,max (+13.6%, P<0.0001), consistent with previous studies, but BMR did not significantly differ between HR and control lines (+6.5%, P=0.181). Additionally, HR mice did not statistically differ from control mice for whole-body lean or fat mass, or for the mass of any organ collected (with body mass as a covariate). Finally, mass-independent V̇O2,max and BMR were uncorrelated (r=0.073, P=0.552) and the only statistically significant correlation with an organ mass was for V̇O2,max and ventricle mass (r=0.285, P=0.015). Overall, our results indicate that selection for a behavioral trait can yield large changes in behavior without proportional modifications to underlying morphological or physiological traits.
more » « less- Award ID(s):
- 2038528
- PAR ID:
- 10508208
- Publisher / Repository:
- Journal of Experimental Biology
- Date Published:
- Journal Name:
- Journal of Experimental Biology
- Volume:
- 226
- Issue:
- 15
- ISSN:
- 0022-0949
- Page Range / eLocation ID:
- jeb245256
- Subject(s) / Keyword(s):
- Basal metabolic rate Behavior Endothermy Energetics Experimental evolution Locomotion
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Uncovering relationships between neuroanatomy, behavior, and evolution are important for understanding the factors that control brain function. Voluntary exercise is one key behavior that both affects, and may be affected by, neuroanatomical variation. Moreover, recent studies suggest an important role for physical activity in brain evolution. We used a unique and ongoing artificial selection model in which mice are bred for high voluntary wheel-running behavior, yielding four replicate lines of high runner (HR) mice that run ∼3-fold more revolutions per day than four replicate nonselected control (C) lines. Previous studies reported that, with body mass as a covariate, HR mice had heavier whole brains, non-cerebellar brains, and larger midbrains than C mice. We sampled mice from generation 66 and used high-resolution microscopy to test the hypothesis that HR mice have greater volumes and/or cell densities in nine key regions from either the midbrain or limbic system. In addition, half of the mice were given 10 weeks of wheel access from weaning, and we predicted that chronic exercise would increase the volumes of the examined brain regions via phenotypic plasticity. We replicated findings that both selective breeding and wheel access increased total brain mass, with no significant interaction between the two factors. In HR compared to C mice, adjusting for body mass, both the red nucleus (RN) of the midbrain and the hippocampus (HPC) were significantly larger, and the whole midbrain tended to be larger, with no effect of wheel access nor any interactions. Linetype and wheel access had an interactive effect on the volume of the periaqueductal gray (PAG), such that wheel access increased PAG volume in C mice but decreased volume in HR mice. Neither linetype nor wheel access affected volumes of the substantia nigra, ventral tegmental area, nucleus accumbens, ventral pallidum (VP), or basolateral amygdala. We found no main effect of either linetype or wheel access on neuronal densities (numbers of cells per unit area) for any of the regions examined. Taken together, our results suggest that the increased exercise phenotype of HR mice is related to increased RN and hippocampal volumes, but that chronic exercise alone does not produce such phenotypes.
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Abstract Bone modeling and remodeling are aerobic processes that entail relatively high oxygen demands. Long bones receive oxygenated blood from nutrient arteries, epiphyseal‐metaphyseal arteries, and periosteal arteries, with the nutrient artery supplying the bulk of total blood volume in mammals (~ 50–70%). Estimates of blood flow into these bones can be made from the dimensions of the nutrient canal, through which nutrient arteries pass. Unfortunately, measuring these canal dimensions non‐invasively (i.e. without physical sectioning) is difficult, and thus researchers have relied on more readily visible skeletal proxies. Specifically, the size of the nutrient artery has been estimated from dimensions (e.g. minimum diameters) of the periosteal (external) opening of the nutrient canal. This approach has also been utilized by some comparative morphologists and paleontologists, as the opening of a nutrient canal is present long after the vascular soft tissue has degenerated. The literature on nutrient arteries and canals is sparse, with most studies consisting of anatomical descriptions from surgical proceedings, and only a few investigating the links between nutrient canal morphology and physiology or behavior. The primary objective of this study was to evaluate femur nutrient canal morphology in mice with known physiological and behavioral differences; specifically, mice from an artificial selection experiment for high voluntary wheel‐running behavior. Mice from four replicate high runner (
HR ) lines are known to differ from four non‐selected control (C) lines in both locomotor and metabolic activity, withHR mice having increased voluntary wheel‐running behavior and maximal aerobic capacity (VO 2max) during forced treadmill exercise. Femora from adult mice (average age 7.5 months) of the 11th generation of this selection experiment were μCT ‐scanned and three‐dimensional virtual reconstructions of nutrient canals were measured for minimum cross‐sectional area as a skeletal proxy of blood flow. Gross observations revealed that nutrient canals varied far more in number and shape than prior descriptions would indicate, regardless of sex or genetic background (i.e.HR vs. C lines). Canals adopted non‐linear shapes and paths as they traversed from the periosteal to endosteal borders through the cortex, occasionally even branching within the cortical bone. Additionally, mice from bothHR and C lines averaged more than four nutrient canals per femur, in contrast to the one to two nutrient canals described for femora from rats, pigs, and humans in prior literature. Mice fromHR lines had significantly larger total nutrient canal area than C lines, which was the result not of an increase in the number of nutrient canals, but rather an increase in their average cross‐section size. This study demonstrates that mice with an evolutionary history of increased locomotor activity and maximal aerobic metabolic rate have a concomitant increase in the size of their femoral nutrient canals. Although the primary determinant of nutrient canal size is currently not well understood, the present results bolster use of nutrient canal size as a skeletal indicator of aerobically supported levels of physical activity in comparative studies. -
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Abstract Objectives Little is known about how ilium cortical bone responds to loading. Using a mouse model, this study presents data testing the hypothesis that iliac cross‐sectional properties are altered in response to increased activity.
Materials and Methods The sample derives from lines of High Runner (HR) mice bred for increased wheel‐running activity. Four treatment groups of female mice were tested: non‐selected control lines housed without (
N = 19) and with wheels (N = 20), and HR mice housed without (N = 17) and with wheels (N = 18) for 13 weeks beginning at weaning. Each pelvis was μCT‐scanned, cross‐sectional properties (cortical area—Ct.Ar , total area—Tt.Ar , polar moment of area, and polar section modulus) were determined from the ilium midshaft, and robusticity indices (ratio of the square root ofCt.Ar orTt.Ar to caudal ilium length) were calculated. Mixed models were implemented with linetype, wheel access, and presence of the mini‐muscle phenotype as fixed effects, replicate line nested within linetype as a random effect, and body mass as a covariate.Results Results demonstrate that the mouse ilium morphologically resembles a long bone in cross section. Body mass and the mini‐muscle phenotype were significant predictors of iliac cross‐sectional properties. Wheel access only had a statistically significant effect on
Ct.Ar and its robusticity index, with greater values in mice with wheel access.Discussion These results suggest that voluntary exercise increases cortical area, but does not otherwise strengthen the ilium in these mice, corroborating previous studies on the effect of increased wheel‐running activity on femoral and humeral cross‐sectional properties in these mice.
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Matsunami, Hiroaki (Ed.)Ethologically relevant chemical senses and behavioral habits are likely to coadapt in response to selection. As olfaction is involved in intrinsically motivated behaviors in mice, we hypothesized that selective breeding for a voluntary behavior would enable us to identify novel roles of the chemosensory system. Voluntary wheel running (VWR) is an intrinsically motivated and naturally rewarding behavior, and even wild mice run on a wheel placed in nature. We have established 4 independent, artificially evolved mouse lines by selectively breeding individuals showing high VWR activity (High Runners; HRs), together with 4 non-selected Control lines, over 88 generations. We found that several sensory receptors in specific receptor clusters were differentially expressed between the vomeronasal organ (VNO) of HRs and Controls. Moreover, one of those clusters contains multiple single-nucleotide polymorphism loci for which the allele frequencies were significantly divergent between the HR and Control lines, i.e., loci that were affected by the selective breeding protocol. These results indicate that the VNO has become genetically differentiated between HR and Control lines during the selective breeding process. Although the role of the vomeronasal chemosensory receptors in VWR activity remains to be determined, the current results suggest that these vomeronasal chemosensory receptors are important quantitative trait loci for voluntary exercise in mice. We propose that olfaction may play an important role in motivation for voluntary exercise in mammals.more » « less
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1242/jeb.245256
