RNA sequencing of poly(A+) transcriptome of quadriceps muscles from wildtype and CaMK2gVV/CaMK2gVV mice under sedentary and post-acute exercise conditions

Reactive oxygen species (ROS) contribute to health and disease. CaMKII is a widely expressed enzyme whose activation by oxidation of regulatory domain methionines (ox-CaMKII) contributes to cardiovascular disease, asthma, and cancer. Here we integrate comparative genomic and experimental data to show that CaMKII activation by ROS arose more than half-a-billion years ago on the vertebrate stem lineage where it constituted a bridge between ROS and increased intracellular Ca2+ release, exercise responsive gene transcription, and improved performance in skeletal muscle.  These enhancements to fight-or-flight physiology were likely key in facilitating a well-evidenced shift in the behavioural ecology of our immediate chordate ancestors, and, in turn, the evolutionary success of vertebrates. Still, the ox-CaMKII innovation must be considered a critical evolutionary trade-off, as it rendered us more susceptible to common and often fatal diseases by providing ROS an expanded role in those processes. This poly(A+) transcriptome profiling study examined the actue transcriptional response of mouse skeletal muscles three hours after a single bout of submaximal exericse in wildtype and mutant mice whose CaMKIIg cannot be activated by reactive oxygen species. Wildtype and CaMK2gVV/CaMK2gVV mice were either kept sedentary or forced to performed a submaximal running exercise. Four mice per genotype were used for each condition. Three hours after the group of exercised mice finished running, all mice were sacrifed for mRNA sequencing by Illumina NovaSeq 6000.