Lab Mice in the Field: Unorthodox Daily Activity and Effects of a Dysfunctional Circadian Clock Allele

Abstract

Daily patterns of animal behavior are potentially of vast functional importance. Fitness benefits have been identified in nature by the association between individual timing and survival or by the fate of individuals after experimental deletion of their circadian pacemaker. The recent advances in unraveling the molecular basis of circadian timing enable new approaches to natural selection on timing. The investigators report on the effect and fate of the mutant Per2 Brdm1 allele in 4 replicate populations of house mice in a seminatural outside environment over 2 years. This allele is known to compromise circadian organization and entrainment and to cause multiple physiological disturbances. Mice (N = 250) bred from Per2Brdm1 heterozygotes were implanted subcutaneously with transponders and released in approximately Mendelian ratios in four 400 m 2 pens. An electronic system stored the times of all visits to feeders of each individual. The study first demonstrates that mice are not explicitly nocturnal in this natural environment. Feeding activity was predominantly and sometimes exclusively diurnal and spread nearly equally over day and night under the protective snow cover in winter. The effect of Per2 Brdm1 on activity timing is negligible compared to seasonal changes in all genotypes. Second, the Per2 Brdm1 allele did not have persistent negative effects on fitness. In the first year, the allele gradually became less frequent by reducing survival. New cohorts captured had the same Per2Brdm1 frequency as the survivors from previous cohorts, consistent with an absence of an effect on reproduction. In the second year, the allele recovered to about its initial frequency (0.54). These changes in selective advantage were primarily due to female mice, as females lived longer and the sex ratio dropped to about 25% males in the population. While it is unknown which selective advantage led to the recovery, the results caution against inferences from laboratory experiments on fitness consequences in the natural environment. It also demonstrates that the activity of mice, while strictly nocturnalPublished in " " which should be cited to refer to this work.

Natural selection against a circadian clock gene mutation in mice

“…However, a causal relationship between diurnality and longevity is unlikely here: During the summer, when the long-living mice from the release cohort (the only ones still present from this cohort) became more diurnal, the population density increased. Diurnal behavior under high population densities is consistent with earlier reports of mice maintained under field conditions (14). Activity during the day may have led to a different predation risk between genotypes.…”

“…Here, despite laboratory studies showing an array of deleterious physiological consequences for health in Per2 Brdm1 (22), there was no overall effect on fitness in outdoor conditions. In contrast to the tau mutation, the Per2 Brdm1 mutation does not strongly affect the circadian period and had a negligible effect on activity patterns in outdoor conditions (14). We cannot exclude the possibility that the effects we report for the tau mutation may be due to an unknown noncircadian pleiotropic effect, even though the earlier laboratory studies on tau mutant hamsters have clearly revealed health consequences as a result of the deleterious impact of inappropriate entrainment to artificial lighting regimes (17).…”

Drosophila circadian rhythms in seminatural environments: Summer afternoon component is not an artifact and requires TrpA1 channels

“…However, recent seminatural studies in mice, hamsters, and Drosophila have revealed some unexpected findings. For example, the widely held belief from laboratory studies that mice and golden hamsters are nocturnal needs to be revised because in the wild they are predominantly or exclusively diurnal (1,2). Similarly in Drosophila melanogaster, locomotor rhythms studied in seminatural conditions reveal that deeply held, laboratory-derived assumptions may require significant revision.…”

Methods in field chronobiology

“…Here, we highlight the methods to translate selection experiments into semi-natural conditions using results from two competition experiments with mice [16,87]. The experiments integrated existing monitoring methods with present-day availability of circadian mutants.…”

“…The mutant and wild-type mice were released into four outdoor enclosures in near Mendelian ratio (homozygote : heterozygote : wild-type ¼ 1 : 2 : 1). However, there was no selection against the mutant allele over the course of two consecutive years [87].…”