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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Trade-offs in muscle physiology in selectively bred high runner mice
ABSTRACT A trade-off between locomotor speed and endurance occurs in various taxa, and is thought to be underpinned by a muscle-level trade-off. Among four replicate high runner (HR) lines of mice, selectively bred for voluntary wheel-running behavior, a negative correlation between average running speed and time spent running has evolved. We hypothesize that this trade-off is due to changes in muscle physiology. We studied the HR lines at generation 90, at which time one line (L3) is fixed for the mini-muscle phenotype, another is polymorphic (L6) and the others (L7, L8) lack mini-muscle individuals. We used in situ preparations to quantify the contractile properties of the triceps surae muscle complex. Maximal shortening velocity varied significantly, being lowest in mini-muscle mice (L3 mini=25.2 mm s−1, L6 mini=25.5 mm s−1), highest in normal-muscle mice L6 and L8 (40.4 and 50.3 mm s−1, respectively) and intermediate in normal-muscle L7 mice (37.2 mm s−1). Endurance, measured both as the slope of the decline in force and the proportion of initial force that could be sustained, also varied significantly. The slope was shallowest in mini-muscle mice (L3 mini=−0.00348, L6 mini=−0.00238), steepest in lines L6 and L8 (−0.01676 and −0.01853), and intermediate in L7 (−0.01145). Normalized sustained force was highest in mini-muscle mice (L3 mini=0.98, L6 mini=0.92) and lowest in L8 (0.36). There were significant, negative correlations between velocity and endurance metrics, indicating a muscle-level trade-off. However, this muscle-level trade-off does not seem to underpin the organismal-level speed and endurance trade-off previously reported as the ordering of the lines is reversed: the lines that run the fastest for the least time have the lowest muscle complex velocity and highest endurance.
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- Award ID(s):
- 2038528
- PAR ID:
- 10417287
- Date Published:
- Journal Name:
- Journal of Experimental Biology
- Volume:
- 225
- Issue:
- 23
- ISSN:
- 0022-0949
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Artificial selection yielded four replicate high runner (HR) lines of mice that reached apparent selection limits (~ threefold increase in wheel revolutions per day vs. four control lines), despite maintenance of additive genetic variance. After 68 generations, we used animal models to test for changes in additive-genetic variances and covariance of the two measured components (average speed and duration) of running distance. We also attempted to break the selection limit by crossing two HR lines, then continuing directional selection on this hybrid line and on the two parental lines for nine generations. The genetic correlation between speed and duration was positive in the base population, but evolved to be negative in the two parental HR lines. Although heritability for both speed and duration (but not distance) increased in the hybrid line, their genetic correlation remained negative. Hybrid F1mice from generation 68 parents showed heterosis for running distance, which was lost in subsequent generations, and the hybrid line did not exceed the limit. Both male and female hybrids ran faster than parental lines for most generations, but running duration was intermediate or reduced, reflecting their negative genetic correlation. The evolved genetic trade-off between speed and duration may explain the inability for the hybrid line to break the selection limit for distance run, despite renewed additive genetic variance for at least one of its component traits.
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Physical inactivity is a scourge to human health, promoting metabolic disease and muscle wasting. Interestingly, multiple ecological niches have relaxed investment into physical activity, providing an evolutionary perspective into the effect of adaptive physical inactivity on tissue homeostasis. One such example, the Mexican cavefish
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We compared the fecal microbial community composition and diversity of four replicate lines of mice selectively bred for high wheel-running activity over 81 generations (HR lines) and four non-selected control (C) lines. We performed 16S rRNA gene sequencing on fecal samples taken 24 hours after weaning, identifying a total of 2,074 bacterial Operational Taxonomic Units. HR and C mice did not significantly differ for measures of alpha diversity, but HR had a higher relative abundance of the family Clostridiaceae. These results differ from a study of rats, where a line bred for high forced-treadmill endurance and that also ran more on wheels had lower relative abundance of Clostridiaceae, as compared with a line bred for low endurance that ran less on wheels. Within the HR and C groups, replicate lines had unique microbiomes based on unweighted UniFrac beta diversity, indicating random genetic drift and/or multiple adaptive responses to selection.
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Abstract Selection experiments can elucidate the varying course of adaptive changes across generations. We examined the appendicular skeleton of house mice from four replicate High Runner (HR) lines bred for physical activity on wheels and four non‐selected Control (C) lines. HR mice reached apparent selection limits between generations 17 and 27, running ~3‐fold more than C. Studies at generations 11, 16, and 21 found that HR mice had evolved thicker hindlimb bones, heavier feet, and larger articular surface areas of the knee and hip joint. Based on biomechanical theory, any or all of these evolved differences may be beneficial for endurance running. Here, we studied mice from generation 68, plus a limited sample from generation 58, to test whether the skeleton continued to evolve after selection limits were reached. Contrary to our expectations, we found few differences between HR and C mice for these later generations, and some of the differences in bone dimensions identified in earlier generations were no longer statistically significant. We hypothesize that the loss of apparently coadapted lower‐level traits reflects (1) deterioration related to a gradual increase in inbreeding and/or (2) additional adaptive changes that replace the functional benefits of some skeletal changes.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1242/jeb.244083
