Patrick A. Carter

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; Hsd:ICR strain) was applied with four high-selected and four control lines (10 families/line). Mice were housed individually with access to activity wheels for a period of 6 days, and selection was based on the mean number of revolutions run on days 5 and 6. Prior to selection, heritabilities of mean revolutions run per day (rev/day), average running velocity (rpm), and number of minutes during which any activity occurred (min/day) were estimated by midparent–offspring regression. Heritabilities were 0.18, 0.28, and 0.14, respectively; the estimate for min/day did not differ significantly from zero. Ten generations of selection for increased rev/day resulted in an average 75% increase in activity in the four selected lines, as compared with control lines. Realized heritability averaged 0.19 (range, 0.12–0.24 for the high-activity lines), or 0.28 when adjusted for within-family selection. Rev/day increased mainly through changes in rpm rather than min/day. These lines will be studied for correlated responses in exercise physiology capacities and will be made available to other researchers on request.

Evolution of a small-muscle polymorphism in lines of house mice selected for high activity levels.

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. Here, we report on organ masses, with emphasis on the triceps surae muscle complex, an important extensor of the ankle. Mice from the selected lines exhibit reduced total body mass, increased relative (mass‐corrected) kidney mass, and reduced relative triceps surae mass. In addition, a discrete muscle‐mass polymorphism was observed: some individuals had triceps surae that were almost 50% lighter than normal for their body mass. This small‐muscle phenotype was observed in only three of the eight lines: in one control line, it has fluctuated in frequency between zero and 10%, whereas in two of the selected lines it has increased in frequency to approximately 50% by generation 22. Data from a set of parents and offspring (generations 23 and 24) are consistent with inheritance as a single autosomal recessive allele. Evidence for the adaptive significance of the small‐muscle allele was obtained by fitting multiple‐generation data to hierarchical models that include effects of genetic drift and/or selection. The small‐muscle allele is estimated to have been present at low frequency (approximately 7%) in the base population, and analysis indicates that strong selection favors the allele in the selected but not control lines. We hypothesize that the small muscles possess functional characteristics and/or that the underlying allele causes pleiotropic effects (e.g., reduced total body mass; increased relative heart, liver, and kidney mass) that facilitate high levels of wheel running. Nevertheless, at generation 22, wheel running of affected individuals did not differ significantly from those with normal‐sized muscles, and the magnitude of response to selection has been similar in all four selected lines, indicating that multiple genetic “solution” are possible in response to selection for high activity levels.

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

We have developed a novel model to study the correlated evolution of behavioural and morphophysiological traits in response to selection for increased locomotor activity. We used selective breeding to increase levels of voluntary wheel running in four replicate lines of laboratory house mice, Mus domesticus, with four random-bred lines maintained as controls. The experiment presented here tested for correlated behavioural responses in the wheel-cage complex, with wheels either free to rotate or locked (environmental factor). After 13 generations, mice from selected lines ran 2.2 times as many revolutions/day as controls on days 5 and 6 of initial exposure to wheels (10 826 versus 4890 revolutions/day, corresponding to 12.1 and 5.5 km/day, respectively). This increase was caused primarily by mice from selected lines running faster, not more minutes per day. Focal-animal observations confirmed that the increase in revolutions/day involved more actual running (or climbing in locked wheels), not an increase in coasting (or hanging). Not surprisingly, access to free versus locked wheels had several effects on behaviour, including total time spent in wheels, sniffing and biting. However, few behaviours showed statistically significant differences between the selected and control lines. Selection did not increase the total time spent in wheels (either free or locked), the frequency of nonlocomotor activities performed in the wheels, nor the amount of locomotor activity in cages attached to the wheels; as well, selection did not decrease the amount of time spent sleeping. Thus, wheel running is, at the genetic level, a largely independent axis of behaviour. Moreover, 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. The selection experiment also offers a new approach to study the proximate mechanisms of wheel-running behaviour itself. For example, frequencies of sniffing and wire biting were reduced in selected females but not males. This result suggests that motivation or function of wheel running may differ between the sexes. Copyright 1999 The Association for the Study of Animal Behaviour.

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

Laboratory house mice (Mus domesticus) that had experienced 10 generations of artificial selection for high levels of voluntary wheel running ran about 70% more total revolutions per day than did mice from random‐bred control lines. The difference resulted primarily from increased average velocities rather than from increased time spent running. Within all eight lines (four selected, four control), females ran more than males. Average daily running distances ranged from 4.4 km in control males to 11.6 km in selected females. Whole‐animal food consumption was statistically indistinguishable in the selected and control lines. However, mice from selected lines averaged approximately 10% smaller in body mass, and mass‐adjusted food consumption was 4% higher in selected lines than in controls. The incremental cost of locomotion (grams food/revolution), computed as the partial regression slope of food consumption on revolutions run per day, did not differ between selected and control mice. On a 24‐h basis, the total incremental cost of running (covering a distance) amounted to only 4.4% of food consumption in the control lines and 7.5% in the selected ones. However, the daily incremental cost of time active is higher (15.4% and 13.1% of total food consumption in selected and control lines, respectively). If wheel running in the selected lines continues to increase mainly by increases in velocity, then constraints related to energy acquisition are unlikely to be an important factor limiting further selective gain. More generally, our 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.

Open-Field Behavior of House Mice Selectively Bred for High Voluntary Wheel-Running

Open-field behavioral assays are commonly used to test both locomotor activity and emotionality in rodents. We performed open-field tests on house mice (Mus domesticus) from four replicate lines genetically selected for high voluntary wheel-running for 22 generations and from four replicate random-bred control lines. Individual mice were recorded by video camera for 3 min in a 1-m2 open-field arena on 2 consecutive days. Mice from selected lines showed no statistical differences from control mice with respect to distance traveled, defecation, time spent in the interior, or average distance from the center of the arena during the trial. Thus, we found little evidence that open-field behavior, as traditionally defined, is genetically correlated with wheel-running behavior. This result is a useful converse test of classical studies that report no increased wheel-running in mice selected for increased open-field activity. However, mice from selected lines turned less in their travel paths than did control-line mice, and females from selected lines had slower travel times (longer latencies) to reach the wall. We discuss these results in the context of the historical open-field test and newly defined measures of open-field activity.

Glucocorticoid Response to Forced Exercise in Laboratory House Mice (Mus domesticus)

We examined the time course and sex differences of the glucocorticoid response to forced, moderate-intensity treadmill exercise in outbred laboratory house mice. Mice (n = 64 total) were divided into eight groups, each of four males and four females, which were run on a motorized treadmill at 1.0 km/h for either 0, 2, 5, 10, 15, 25, 40, or 60 min. Serum samples were taken immediately after exercise and corticosterone (CORT) concentration was determined by radioimmunoassay. Resting CORT levels ranged between 11.6 and 29.5 ng/mL for both sexes. CORT levels increased with length of exercise and then exhibited a plateau by 25 min in females and by 40 min in males. Females displayed a significantly more rapid increase in serum CORT levels and attained higher maximal CORT levels than males. Females also had significantly larger adrenal glands, both in absolute terms and relative to body mass.

Body temperatures of house mice artificially selected for high voluntary wheel-running behavior: repeatability and effect of genetic selection.

We studied rectal body temperatures of house mice (Mus domesticus) that had been artificially selected for high voluntary wheel running.1. At generation 17, mice from the four replicate selected lines ran, on average, 2.5-times as many revolutions/day as did mice from the four random-bred control lines.2. During the day, repeatability of individual differences in body temperature measured 4 days apart was low; at night, repeatability was statistically significant across three time scales (1 day, 1 week, 2 weeks).3. During the day, body temperatures of selected and control animals did not differ; at night, mice from selected lines had higher body temperatures. However, when amount of wheel running immediately prior to measurement was included as a covariate, the difference was no longer statistically significant.Higher body temperatures, associated with increased activity, might enhance locomotor abilities through Q10 effects, increase metabolic rate and food requirements, affect sleep patterns, and alter expression of heat-shock proteins.

Limits to behavioral evolution: the quantitative genetics of a complex trait under directional selection.

Replicated selection experiments provide a powerful way to study how “multiple adaptive solutions” may lead to differences in the quantitative–genetic architecture of selected traits and whether this may translate into differences in the timing at which evolutionary limits are reached. We analyze data from 31 generations (n = 17,988) of selection on voluntary wheel running in house mice. The rate of initial response, timing of selection limit, and height of the plateau varied significantly between sexes and among the four selected lines. Analyses of litter size and realized selection differentials seem to rule out counterposing natural selection as a cause of the selection limits. Animal‐model analyses showed that although the additive genetic variance was significantly lower in selected than control lines, both before and after the limits, the decrease was not sufficient to explain the limits. Moreover, directional selection promoted a negative covariance between additive and maternal genetic variance over the first 10 generations. These results stress the importance of replication in selection studies of higher‐level traits and highlight the fact that long‐term predictions of response to selection are not necessarily expected to be linear because of the variable effects of selection on additive genetic variance and maternal effects.

ONTOGENIES IN MICE SELECTED FOR HIGH VOLUNTARY WHEEL‐RUNNING ACTIVITY. I. MEAN ONTOGENIES

Abstract The evolutionary importance of postnatal ontogenies has long been recognized, but most studies of ontogenetic trajectories have focused exclusively on morphological traits. For animals, this represents a major omission because behavioral traits and their ontogenies often have relatively direct relationships to fitness. Here four replicate lines of house mice artificially selected for high early‐age wheel running and their four replicate control lines were used to evaluate the effects of early‐age directional selection, genetic drift, and activity environment (presence or absence of a running wheel) on variation in the ontogenies of three traits known to be genetically correlated: voluntary wheel running, body mass, and food consumption. Early‐age selection significantly changed both the shape and position of the wheel‐running and food‐consumption ontogenies while influencing the position, but not the shape, of the body mass ontogeny. Genetic drift (as indicated by variation among replicate lines) produced significant changes in both the position and shape of all three ontogenies; however, its effect differed between the selection and control groups. For wheel running and food consumption, genetic drift only influenced the control ontogenies, whereas for body mass, genetic drift had a significant effect in both selection groups. Both body‐mass and food‐consumption ontogenies were significantly altered by activity environment, with the environment causing significant changes in the shape and position of both ontogenies. Overall the results demonstrate strong effects of early‐age selection, genetic drift, and environmental variation on the evolution and expression of behavioral and morphological ontogenies, with selection changing only the position of the morphological ontogeny but both the position and shape of the behavioral ontogenies.

Nesting Behavior of House Mice (Mus Domesticus) Selected for Increased Wheel-Running Activity

Nest building was measured in “active” (housed with access to running wheels) and “sedentary” (without wheel access) mice (Mus domesticus) from four replicate lines selected for 10 generations for high voluntary wheel-running behavior, and from four randombred control lines. Based on previous studies of mice bidirectionally selected for thermoregulatory nest building, it was hypothesized that nest building would show a negative correlated response to selection on wheel-running. Such a response could constrain the evolution of high voluntary activity because nesting has also been shown to be positively genetically correlated with successful production of weaned pups. With wheel access, selected mice of both sexes built significantly smaller nests than did control mice. Without wheel access, selected females also built significantly smaller nests than did control females, but only when body mass was excluded from the statistical model, suggesting that body mass mediated this correlated response to selection. Total distance run and mean running speed on wheels was significantly higher in selected mice than in controls, but no differences in amount of time spent running were measured, indicating a complex cause of the response of nesting to selection for voluntary wheel running.