Abstract Replicate lines under uniform selection often evolve in different ways. Previously, analyses using whole-genome sequence data for individual mice (Mus musculus) from 4 replicate High Runner lines and 4 nonselected control lines demonstrated genomic regions that have responded consistently to selection for voluntary wheel-running behavior. Here, we ask whether the High Runner lines have evolved differently from each other, even though they reached selection limits at similar levels. We focus on 1 High Runner line (HR3) that became fixed for a mutation at a gene of major effect (Myh4Minimsc) that, in the homozygous condition, causes a 50% reduction in hindlimb muscle mass and many pleiotropic effects. We excluded HR3 from SNP analyses and identified 19 regions not consistently identified in analyses with all 4 lines. Repeating analyses while dropping each of the other High Runner lines identified 12, 8, and 6 such regions. (Of these 45 regions, 37 were unique.) These results suggest that each High Runner line indeed responded to selection somewhat uniquely, but also that HR3 is the most distinct. We then applied 2 additional analytical approaches when dropping HR3 only (based on haplotypes and nonstatistical tests involving fixation patterns). All 3 approaches identified 7 new regions (as compared with analyses using all 4 High Runner lines) that include genes associated with activity levels, dopamine signaling, hippocampus morphology, heart size, and body size, all of which differ between High Runner and control lines. Our results illustrate how multiple solutions and “private” alleles can obscure general signatures of selection involving “public” alleles.
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Genetic Basis of Aerobically Supported Voluntary Exercise: Results from a Selection Experiment with House Mice
Abstract House mice from 4 replicate lines selectively bred for 61 generations for voluntary wheel-running behavior were compared with 4 non-selected control lines using multiple genome-wide analytical techniques on both haplotype and single nucleotide polymorphism data......
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- Award ID(s):
- 1655362
- PAR ID:
- 10287758
- Date Published:
- Journal Name:
- Genetics
- Volume:
- 216
- Issue:
- 3
- ISSN:
- 1943-2631
- Page Range / eLocation ID:
- 781 to 804
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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