author={Theodore Garland and Martin T. Morgan and John G. Swallow and Justin S Rhodes and Isabelle Girard and Jason G. Belter and Patrick A. Carter},
Abstract To study the correlated evolution of locomotor behavior and exercise physiology, we conducted an artificial selection experiment. From the outbred Hsd:ICR strain of Mus domesticus, we began eight separate lines, each consisting of 10 breeding pairs. In four of the lines, we used within‐family selection to increase voluntary wheel running. The remaining four lines were random‐bred (within lines) to serve as controls. Various traits have been monitored to test for correlated responses… 

Artificial selection for high activity favors mighty mini-muscles in house mice.

The results demonstrate that during selection for voluntary wheel running, distinct adaptive paths that differentially exploit the genetic variation in morphological and physiological traits have been followed.

Phenotypic and Evolutionary Plasticity of Organ Masses in Response to Voluntary Exercise in House Mice1

The mini-muscle phenotype, caused by a Mendelian recessive allele that halves hindlimb muscle mass, was significantly associated with several other body composition traits, including reduced bodymass, increased tail length, increased heart mass, increased liver mass (females only), increased mean adrenal gland mass, and reduced Hct (wheel-access females only).

Selective breeding as a tool to probe skeletal response to high voluntary locomotor activity in mice.

A novel mouse-model based on selective breeding for high levels of voluntary wheel running is presented, and it is hypothesized that a reduction of myosin heavy-chain type-IIb isoforms with accounts for the observed ontogenetic changes in muscle mass.

Rapid and longer‐term effects of selective breeding for voluntary exercise behavior on skeletal morphology in house mice

The appendicular skeleton of house mice from four replicate High Runner lines bred for physical activity on wheels and four non‐selected Control lines was examined, finding 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.

Locomotor trade-offs in mice selectively bred for high voluntary wheel running

Mini-muscle mice had higher COT, mainly because of higher zero-speed intercepts and postural costs (intercept–resting metabolic rate), contrary to predictions, mice with altered limb morphology after intense selection for running long distances do not necessarily run more economically.

Evolution of hindlimb bone dimensions and muscle masses in house mice selectively bred for high voluntary wheel‐running behavior

Skeletal dimensions and muscle masses can evolve rapidly in response to directional selection on locomotor behavior in house mice bred for high levels of voluntary wheel running with four non‐selected control lines is demonstrated.

Experimental evolution and phenotypic plasticity of hindlimb bones in high‐activity house mice

It is shown that phylogenetic analyses of previously published data indicate a positive correlation between body mass‐corrected home range area and both hindlimb length and metatarsal/femur ratio in a sample of 19 species of Carnivora, although only the former is statistically significant in a multiple regression.

Genetic Basis of Aerobically Supported Voluntary Exercise: Results from a Selection Experiment with House Mice

Results indicate that selective breeding for high voluntary exercise has resulted in changes in allele frequencies for multiple genes associated with both motivation and ability for endurance exercise, providing candidate genes that may explain phenotypic changes observed in previous studies.


It is suggested that relatively small changes in the expression patterns of hippocampal genes underlie large changes in phenotypic response to selection, and that the genetic architecture of running motivation likely involves the dopaminergic system as well as CNS signaling machinery.

Effects of voluntary exercise and genetic selection for high activity levels on HSP72 expression in house mice.

Examination of expression of heat shock protein 72 in female mice from four replicate lines that had been selectively bred for high voluntary wheel running (S) and from four random-bred control lines (C) indicated that S mice had significantly elevated HSP72 expression only when housed with free wheels, which is not a simple proximate effect of their increased wheel running.



Effects of voluntary activity and genetic selection on muscle metabolic capacities in house mice Mus domesticus.

Genetic selection for increased voluntary wheel running did not reduce the capability of muscle aerobic capacity to respond to training, as indicated by higher levels of mitochondrial and glycolytic enzymes and gender-specific responses.

Artificial selection for increased wheel-running activity in house mice results in decreased body mass at maturity.

An artificial selection experiment for increased voluntary wheel-running activity in house mice (Mus domesticus) is conducted to test the hypothesis that body size and activity levels are negatively genetically correlated and to compare body masses of mice from control and selected lines after 14 generations of selection.

Behaviour of house mice artificially selected for high levels of voluntary wheel running

Wheel running is, at the genetic level, a largely independent axis of behaviour, and the genetic architecture of overall wheel running and its components seem conducive to increasing total distance moved without unduly increasing energy or time-related costs.

Artificial Selection for Increased Wheel-Running Behavior in House Mice

Replicated within-family selection for increased voluntary wheel running in outbred house mice (Mus domesticus) was applied with four high-selected and four control lines (10 families/line) and resulted in an average 75% increase in activity in the four selected lines, as compared with control lines.

Energy Cost of Wheel Running in House Mice: Implications for Coadaptation of Locomotion and Energy Budgets

The results suggest that, in small mammals, a substantial evolutionary increase in daily movement distances can be achieved by increasing running speed, without remarkable increases in total energy expenditure.

Effects of voluntary activity and genetic selection on aerobic capacity in house mice (Mus domesticus).

The results suggest the existence of a possible genetic correlation between voluntary activity levels (behavior) and aerobic capacity (physiology), and nests two-way analysis of covariance demonstrated that both genetic selection history and access to wheels had significant positive effects on VO2max.

Exercise physiology of wild and random-bred laboratory house mice and their reciprocal hybrids.

In general, the behavioral and/or whole organisms performance traits showed greater differences than the lower-level traits; thus, during the domestication of house mice, behavior may have evolved more rapidly than physiology.

Food consumption and body composition in mice selected for high wheel-running activity

The effects of genetic selection for high wheel running (13th generation) and prolonged access to running wheels on food consumption and body composition were studied in house mice and found a significant interaction between selection and wheel access treatments.

Multiple selection responses in house mice bidirectionally selected for thermoregulatory nest-building behavior: Crosses of replicate lines

The reciprocal F1 crosses showed significant heterosis for nest-building behavior compared to the contemporaneous generations of the parental lines, which support earlier findings that larger nests are closely related to fitness.