UC Riverside

Populations under directional selection may reach a selection limit after which they no longer respond to selection. This dissertation examined four possible genetic and/or physiological causes of selection limits reached in four replicate lines of mice bred for high voluntary wheel running (HR lines).

Chapter 1 used individual locus models to test the hypothesis that “phenotypic epistasis” (non-additive interactions among components of a trait) can allow maintenance of additive genetic variance (VA) for a complex behavioral trait at a selection limit. Models with phenotypic epistasis but purely additive genetic effects on component traits involving motivation and ability for speed and duration of running did not maintain VA, nor did genetic dominance or pleiotropy. However, models with genetic antagonistic pleiotropy did sometimes allow maintenance of VA.

Chapter 2 attempted to break the selection limits in HR lines by use of a hybrid cross with continued selection on it and the parental HR lines. The hybrid line did not break the limit for daily running distance. The genetic correlation between running duration and speed evolved from positive in the starting population to negative in the parental lines, and remained so in the hybrid line, which represents a type of genetic constraint.

Chapter 3 studied body composition (i.e., lean and fat mass) of mice before and after 6 days of wheel access. Despite increased exercise, HR lines lost less fat, indicating that preserving a baseline fat mass may be a limiting factor in HR locomotor activity.

Chapter 4 examined energetic perturbations imposed in early-life. Dams were given high-fat, high-sugar "Western" diet (WD) or standard chow from 2 weeks prior to pairing until pups were 14 days of age, when all mice were switched to standard chow. From weaning to adulthood, offspring received physiological and behavioral tests. Maternal WD increased juvenile home-cage activity for both HR and C mice (only males tested). Maternal WD also increased fat and lean masses of adult mice, but 6 days of wheel access reversed the effect on fat. Offspring of dams given WD did not increase wheel running, indicating that fat availability itself does not increase wheel running.