An official website of the United States government
ABSTRACT Selection experiments play an increasingly important role in comparative and evolutionary physiology. However, selection experiments can be limited by relatively low statistical power, in part because replicate line is the experimental unit for analyses of direct or correlated responses (rather than number of individuals measured). One way to increase the ability to detect correlated responses is through a meta-analysis of studies for a given trait across multiple generations. To demonstrate this, we applied meta-analytic techniques to two traits (body mass and heart ventricle mass, with body mass as a covariate) from a long-term artificial selection experiment for high voluntary wheel-running behavior. In this experiment, all four replicate High Runner (HR) lines reached apparent selection limits around generations 17–27, running approximately 2.5- to 3-fold more revolutions per day than the four non-selected Control (C) lines. Although both traits would also be expected to change in HR lines (relative heart size expected to increase, expected direction for body mass is less clear), their statistical significance has varied, despite repeated measurements. We compiled information from 33 unique studies and calculated a measure of effect size (Pearson's R). Our results indicate that, despite a lack of statistical significance in most generations, HR mice have evolved larger hearts and smaller bodies relative to controls. Moreover, plateaus in effect sizes for both traits coincide with the generational range during which the selection limit for wheel-running behavior was reached. Finally, since reaching the selection limit, absolute effect sizes for body mass and heart ventricle mass have become smaller (i.e. closer to 0).
more »
« less
Selective breeding for high voluntary exercise in mice increases maximal ( V̇ O2,max) but not basal metabolic rate
ABSTRACT 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
More Like this
-
-
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.more » « less
-
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.more » « less
-
How traits at multiple levels of biological organization evolve in a correlated fashion in response to directional selection is poorly understood, but two popular models are the very general “behavior evolves first” (BEF) hypothesis and the more specific “morphology-performance-behavior-fitness” (MPBF) paradigm. Both acknowledge that selection often acts relatively directly on behavior and that when behavior evolves, other traits will as well but most with some lag. However, this proposition is exceedingly difficult to test in nature. Therefore, we studied correlated responses in the high-runner (HR) mouse selection experiment, in which four replicate lines have been bred for voluntary wheel-running behavior and compared with four non-selected control (C) lines. We analyzed a wide range of traits measured at generations 20–24 (with a focus on new data from generation 22), coinciding with the point at which all HR lines were reaching selection limits (plateaus). Significance levels (226 P values) were compared across trait types by ANOVA, and we used the positive false discovery rate to control for multiple comparisons. This meta-analysis showed that, surprisingly, the measures of performance (including maximal oxygen consumption during forced exercise) showed no evidence of having diverged between the HR and C lines, nor did any of the life history traits (e.g., litter size), whereas body mass had responded (decreased) at least as strongly as wheel running. Overall, results suggest that the HR lines of mice had evolved primarily by changes in motivation rather than performance ability at the timethey were reaching selection limits. In addition, neither the BEF model nor the MPBF model of hierarchical evolution provides a particularly good fit to theHRmouse selection experiment.more » « less
-
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
- Free Publicly Accessible Full Text
-
Accepted Manuscript
- Journal Article:
- https://doi.org/10.1242/jeb.245256
