John G. Swallow

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.

The long and short of sperm polymorphisms in insects

Production of more than one morphological type of sperm in a common testis has been documented for a variety of invertebrates, including gastropods, spiders, centipedes, and insects. This unusual phenomenon is diffcult to explain by current theory, particularly since available evidence indicates that one sperm type is often incapable of effecting fertilization. In this review we critically examine evidence on the distribution and development of sperm heteromorphisms among insects in light of competing hypotheses for the evolutionary origin, maintenance, and function of a non‐fertilizing class of sperm. To date, no single hypothesis, including alternatives which assume non‐fertilizing sperm are non‐adaptive, or that they provision, facilitate, or compete with fertilizing sperm, has received strong empirical support by any group of insects. The diversity of sperm heteromorphisms suggests that non‐fertilizing sperm may have different functions in different clades or even serve multiple functions within a clade. We suggest that insight could be gained from (1) new models for the evolution of sperm polymorphism, (2) comparative studies that focus on multiple traits simultaneously (e.g. sperm number, proportion, length, and remating rate) and utilize clades in which more than one gain or loss of sperm heteromorphism has been documented (e.g. Pentatomidae, Carabidae, or Diopsidae), and (3) experimental studies that exploit individual variation or directly manipulate the composition of the male ejaculate.

Quantitative Genetics of Locomotor Speed and Endurance in the Lizard Lacerta vivipara

We used quantitative genetic analyses to test the hypothesis of a trade-of between locomotor speed and endurance in a population of the European lizard Lacerta vivipara, which is the subject of long-term demographic studies. We estimated the heritability of maximal sprint speed, treadmill endurance, and tail length, a morphometric trait that may afect locomotor performance, as well asphenotypic, genetic, and environmental correlations between these traits. Gravid females were captured in the field and held in the laboratory under standardized conditions until giving birth; traits were then measured on their ofspring. Prior to genetic analyses, we used multiple regressions to remove the efects of such covariates as body size (mass and snout-vent length), dam age, and length of time dams were held in captivity prior toparturition. When we examined the residual characters, heritability was low and statistically nonsignficant for speed but relatively high for both endurance (0.46) and tail length (0.51). None of the phenotypic, genetic, or environmental correlations between traits was statistically significant. Thus, we found no evidence for a trade-off between speed and endurance; these results are consistent with those reported in two previous studies of squamate reptiles (the garter snake Thamnophis sirtalis and the fence lizard Sceloporus occidentalis). The lack of a negative genetic correlation between speed and endurance suggests that these aspects of locomotor abilities are relatively free to evolve independently, such that natural selection could increase both speed and endurance. However, the species studied to date have low to moderate capacities for speed and endurance, as compared with other squamates. Physiologically based trade-offs-for example, those caused by the composition ofmuscle fiber types-should be more likely to exist in species that have high capacities for speed and/or endurance.

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.

Phenotypic and evolutionary plasticity of organ masses in response to voluntary exercise in house mice.

Abstract We used a novel mouse model to study the effects of selective breeding for high locomotor activity (14 generations) on relative organ sizes, hematocrit (Hct), and blood hemoglobin (Hb) concentration. We also examined effects of exercise training and genotype-by-environment interactions by housing animals for 8 weeks with wheels that were either free to rotate or locked. Mice from the four replicate High-Runner (HR) lines were smaller in total body mass but had larger body mass-adjusted kidneys relative to the four Control lines (P < 0.05). Control and HR lines did not differ significantly for mass-adjusted tail length or masses of the “triceps surae” hindlimb muscle group, heart (ventricle), spleen, liver, adrenal glands or gonads. Wheel access caused a reduction in body mass and an increase in relative heart mass. In females only, wheel access caused a reduction in relative spleen mass. Wheel access did not affect relative tail length or relative mass of the triceps surae, liver, adrenal gland or gonads. Significant interactions between selection history and wheel access were observed in females for spleen, liver, and gonad mass as well as Hct and Hb. Wheel access caused increases in both Hct and Hb, mainly in the HR lines. 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 body mass, increased tail length, increased heart mass, increased liver mass (females only), increased mean adrenal gland mass (females only), increased mean kidney mass (males only), and reduced Hct (wheel-access females only). Results are discussed in context of the beneficial acclimation hypothesis, genotype-by-environment interactions, and the potential for “nurture” to be self-reinforcing of “nature” in some complex behavioral-physiological phenotypes.

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.

Effects of Excessive Long-Term Exercise on Cardiac Function and Myocyte Remodeling in Hypertensive Heart Failure Rats

The long-term effects of exercise on cardiac function and myocyte remodeling in hypertension/progression of heart failure are poorly understood. We investigated whether exercise can attenuate pathological remodeling under hypertensive conditions. Fifteen female Spontaneously Hypertensive Heart Failure rats and 10 control rats were housed with running wheels beginning at 6 months of age. At 22 months of age, heart function of the trained rats was compared with heart function of age-matched sedentary hypertensive and control rats. Heart function was measured using echocardiography and left ventricular catheterization. Cardiac myocytes were isolated to measure cellular dimensions. Fetal gene expression was determined using Western blots. Exercise did not significantly impact myocyte remodeling or ventricular function in control animals. Sedentary hypertensive rats had significant chamber dilatation and cardiac hypertrophy. In exercised hypertensive rats, however, exercise time was excessive and resulted in a 21% increase in left ventricular diastolic dimension (P<0.001), a 24% increase in heart to body weight ratio (P<0.05), a 27% increase in left ventricular myocyte volume (P<0.01), a 13% reduction in ejection fraction (P<0.001), and a 22% reduction in fractional shortening (P<0.01) compared with sedentary hypertensive rats. Exercise resulted in greater fibrosis and did not prevent activation of the fetal gene program in hypertensive rats. We conclude that excessive exercise, in the untreated hypertensive state can have deleterious effects on cardiac remodeling and may actually accelerate the progression to heart failure.