. Effects of voluntary activity and genetic selection on aerobic capacity in house mice (Mus domesticus). J. Appl. Physiol. 84(1): 69-76, 1998.-An animal model was developed to study effects on components of exercise physiology of both ''nature'' (10 generations of genetic selection for high voluntary activity on running wheels) and ''nurture'' (7-8 wk of access or no access to running wheels, beginning at weaning). At the end of the experiment, mice from both wheel-access groups were significantly lighter in body mass than mice from sedentary groups. Within the wheel-access group, a statistically significant, negative relationship existed between activity and final body mass. In measurements of maximum oxygen consumption during forced treadmill exercise (V O 2 max ), mice with wheel access were significantly more cooperative than sedentary mice; however, trial quality was not a significant predictor of individual variation in V O 2 max . Nested two-way analysis of covariance demonstrated that both genetic selection history and access to wheels had significant positive effects on V O 2 max . A 12% difference in V O 2 max existed between wheelaccess selected mice, which had the highest mass-corrected V O 2 max , and sedentary control mice, which had the lowest. The respiratory exchange ratio at V O 2 max was also significantly lower in the wheel-access group. Our results suggest the existence of a possible genetic correlation between voluntary activity levels (behavior) and aerobic capacity (physiology).

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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 "solutions" are possible in response to selection for high activity levels.

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.

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