Epistatic interactions of genes influence within-individual variation of physical activity traits in mice

A number of quantitative trait loci (QTLs) recently have been discovered that affect various activity traits in mice, but their collective impact does not appear to explain the consistently moderate to high heritabilities for these traits. We previously suggested interactions of genes, or epistasis, might account for additional genetic variability of activity, and tested this for the average distance, duration and speed run by mice during a 3 week period. We found abundant evidence for epistasis affecting these traits, although, recognized that epistatic effects may well vary within individuals over time. We therefore conducted a full genome scan for epistatic interactions affecting these traits in each of seven three-day intervals. Our intent was to assess the extent and trends in epistasis affecting these traits in each of the intervals. We discovered a number of epistatic interactions of QTLs that influenced the activity traits in the mice, the majority of which were not previously found and appeared to affect the activity traits (especially distance and speed) primarily in the early or in the late age intervals. The overall impact of epistasis was considerable, its contribution to the total phenotypic variance varying from an average of 22–35% in the three traits across all age intervals. It was concluded that epistasis is more important than single-locus effects of genes on activity traits at specific ages and it is therefore an essential component of the genetic architecture of physical activity

Why Control Activity? Evolutionary Selection Pressures Affecting the Development of Physical Activity Genetic and Biological Regulation

The literature strongly suggests that daily physical activity is genetically and biologically regulated. Potential identities of the responsible mechanisms are unclear, but little has been written concerning the possible evolutionary selection pressures leading to the development of genetic/biological controls of physical activity. Given the weak relationship between exercise endurance and activity levels and the differential genomic locations associated with the regulation of endurance and activity, it is probable that regulation of endurance and activity evolved separately. This hypothesis paper considers energy expenditures and duration of activity in hunter/gatherers, pretechnology farmers, and modern Western societies and considers the potential of each to selectively influence the development of activity regulation. Food availability is also considered given the known linkage of caloric restriction on physical activity as well as early data relating food oversupply to physical inactivity. Elucidating the selection pressures responsible for the genetic/biological control of activity will allow further consideration of these pressures on activity in today’s society, especially the linkages between food and activity. Further, current food abundance is removing the cues for activity that were present for the first 40,000 years of human evolution, and thus future research should investigate the effects of this abundance upon the mechanisms regulating activity

Genetic variation for body weight change in mice in response to physical exercise

Abstract Background Physical activity is beneficial in reducing the weight gain and associated health problems often experienced by individuals as they age, but the association of weight change with physical activity remains complex. We tested for a possible genetic basis for this association between 9-12-week body weight change (WTC) and the distance, duration, and speed voluntarily run by 307 mice in an F2 population produced from an intercross of two inbred strains (C57L/J and C3H/HeJ) that differed dramatically in their physical activity levels. Results In this population WTC did show the expected negative association with the physical activity traits, but only the phenotypic correlation of WTC with speed (-0.18) reached statistical significance. Using an interval mapping approach with single-nucleotide polymorphism markers, we discovered five (four suggestive and one significant) quantitative trait loci (QTLs) affecting body weight change, only one of which appeared to show pleiotropic effects on the physical activity traits as well. Genome-wide epistasis scans also detected several pairwise interactions of QTLs with pleiotropic effects on WTC and the physical activity traits, but these effects made a significant contribution (51%) only to the covariance of WTC with speed. Conclusion It was concluded that the genetic contribution to the phenotypic association between WTC and the physical activity traits in this population of mice was primarily epistatic in origin, restricted to one measure of physical activity, and could be quite variable among different populations depending on the genetic background, experimental design and traits assessed

Differential Gene Expression in High- and Low-Active Inbred Mice

Numerous candidate genes have been suggested in the recent literature with proposed roles in regulation of voluntary physical activity, with little evidence of these genes' functional roles. This study compared the haplotype structure and expression profile in skeletal muscle and brain of inherently high- (C57L/J) and low- (C3H/HeJ) active mice. Expression of nine candidate genes [Actn2, Actn3, Casq1, Drd2, Lepr, Mc4r, Mstn, Papss2, and Glut4 (a.k.a. Slc2a4)] was evaluated via RT-qPCR. SNPs were observed in regions of Actn2, Casq1, Drd2, Lepr, and Papss2; however, no SNPs were located in coding sequences or associated with any known regulatory sequences. In mice exposed to a running wheel, Casq1 (P = 0.0003) and Mstn (P = 0.002) transcript levels in the soleus were higher in the low-active mice. However, when these genes were evaluated in naïve animals, differential expression was not observed, demonstrating a training effect. Among naïve mice, no genes in either tissue exhibited differential expression between strains. Considering that no obvious SNP mechanisms were determined or differential expression was observed, our results indicate that genomic structural variation or gene expression data alone is not adequate to establish any of these genes' candidacy or causality in relation to regulation of physical activity

Wicked Good Sports Medicine Symposium 2012 Program

2012 sports medicine symposium at the University of New England in Biddeford, Maine. Presenters and topics included: Daniel E. Lieberman: Why Exercise Really is Medicine (An Evolutionary Explanation); Samuel Headley: Exercise and Chronic Kidney Disease; Stella L. Volpe: Prevention of Weight Gain in a Large Portion Society; J. Timothy Lightfoot: Can You Be Born a Couch Potato? The Genetics that Control Your Physical Activity; Samuel N. Cheuvront: Answers to 10 Common Questions about Hydration; David Epstein: Missing the Phenotypes for the Genotypes.https://dune.une.edu/wgsms/1000/thumbnail.jp

Quantitative trait loci for physical activity traits in mice

The genomic locations and identities of the genes that regulate voluntary physical activity are presently unknown. The purpose of this study was to search for quantitative trait loci (QTL) that are linked with daily mouse running wheel distance, duration, and speed of exercise. F2 animals (n = 310) derived from high active C57L/J and low active C3H/HeJ inbred strains were phenotyped for 21 days. After phenotyping, genotyping with a fully informative single-nucleotide polymorphism panel with an average intermarker interval of 13.7 cM was used. On all three activity indexes, sex and strain were significant factors, with the F2 animals similar to the high active C57L/J mice in both daily exercise distance and duration of exercise. In the F2 cohort, female mice ran significantly farther, longer, and faster than male mice. QTL analysis revealed no sex-specific QTL but at the 5% experimentwise significance level did identify one QTL for duration, one QTL for distance, and two QTL for speed. The QTL for duration (DUR13.1) and distance (DIST13.1) colocalized with the QTL for speed (SPD13.1). Each of these QTL accounted for ∼6% of the phenotypic variance, whereas SPD9.1 (chromosome 9, 7 cM) accounted for 11.3% of the phenotypic variation. DUR13.1, DIST13.1, SPD13.1, and SPD9.1 were subsequently replicated by haplotype association mapping. The results of this study suggest a genetic basis of voluntary activity in mice and provide a foundation for future candidate gene studies

Species-specific molecular responses of wild coral reef fishes during a marine heatwave

The marine heatwave of 2016 was one of the longest and hottest thermal anomalies recorded on the Great Barrier Reef, influencing multiple species of marine ectotherms, including coral reef fishes. There is a gap in our understanding of what the physiological consequences of heatwaves in wild fish populations are. Thus, in this study, we used liver transcriptomes to understand the molecular response of five species to the 2016 heatwave conditions. Gene expression was species specific, yet we detected overlap in functional responses associated with thermal stress previously reported in experimental setups. The molecular response was also influenced by the duration of exposure to elevated temperatures. This study highlights the importance of considering the effects of extreme warming events when evaluating the consequences of climate change on fish communities