Mitochondrial DNA haplotype association in mice selectively bred for high voluntary wheel running

Abstract

Mitochondrial DNA (mtDNA) haplotypes have been associated with various human and rodent phenotypes, such as nonshivering thermogenesis capacity, learning capability, and disease risk. Although the mammalian mtDNA control region (D‐loop) is highly polymorphic, D‐loops in laboratory mice are apparently identical, and variation occurs elsewhere in the mitochondrial genome – mainly between nucleotide base pairs 9820 and 9830. In fact, this region has been associated with reactive oxygen species (ROS) production. We hypothesized that the capacity for high levels of wheel running activity would be associated with mtDNA haplotype. To test this, we analyzed the polymorphic region of the mitochondrial genome in ~ 10 mice from each of 4 replicate lines selectively bred for 54 generations for high voluntary wheel running and from 4 non‐selected control lines. Sequencing of this polymorphic region revealed a variable number of adenine repeat insertions within and among the lines of mice. Four lines were fixed with 9 adenine repeats, two were fixed with 10, and 2 were variable with 9–11 adenine repeat insertions. These adenine repeat insertions will be tested for correlations with body mass, litter size, and wheel running activity. This system may provide an experimental model to dissect the physiological processes linking mtDNA single nucleotide polymorphisms to exercise activity. Supported by NSF IOS‐1121273 to TG.