CaMKII oxidation is a critical performance/disease trade-off acquired at the dawn of vertebrate evolution
Journal
Nature Communications
Journal Volume
12
Journal Issue
1
Date Issued
2021
Author(s)
Abstract
Antagonistic pleiotropy is a foundational theory that predicts aging-related diseases are the result of evolved genetic traits conferring advantages early in life. Here we examine CaMKII, a pluripotent signaling molecule that contributes to common aging-related diseases, and find that its activation by reactive oxygen species (ROS) was acquired more than half-a-billion years ago along the vertebrate stem lineage. Functional experiments using genetically engineered mice and flies reveal ancestral vertebrates were poised to benefit from the union of ROS and CaMKII, which conferred physiological advantage by allowing ROS to increase intracellular Ca2+ and activate transcriptional programs important for exercise and immunity. Enhanced sensitivity to the adverse effects of ROS in diseases and aging is thus a trade-off for positive traits that facilitated the early and continued evolutionary success of vertebrates. ? 2021, The Author(s).
Subjects
cell component; detection method; experimental study; genetic analysis; oxidation; pleiotropy; reactive oxygen species; vertebrate; Vertebrata; calcium calmodulin dependent protein kinase II; Drosophila protein; reactive oxygen metabolite; aging; animal; animal model; calcium signaling; CRISPR Cas system; Drosophila melanogaster; evolution; female; fitness; gene editing; gene knock-in; genetics; male; metabolism; mouse; oxidation reduction reaction; phylogeny; physiology; point mutation; transgenic animal; vertebrate; Aging; Animals; Animals, Genetically Modified; Biological Evolution; Calcium Signaling; Calcium-Calmodulin-Dependent Protein Kinase Type 2; CRISPR-Cas Systems; Drosophila melanogaster; Drosophila Proteins; Female; Gene Editing; Gene Knock-In Techniques; Male; Mice; Models, Animal; Oxidation-Reduction; Phylogeny; Physical Fitness; Point Mutation; Reactive Oxygen Species; Vertebrates
SDGs
Other Subjects
calcium calmodulin dependent protein kinase II; reactive oxygen metabolite; calcium calmodulin dependent protein kinase II; Drosophila protein; cell component; detection method; experimental study; genetic analysis; oxidation; pleiotropy; reactive oxygen species; vertebrate; aging; animal experiment; animal tissue; antagonistic pleiotropy; Article; calcium cell level; calcium signaling; cell lineage; clustered regularly interspaced short palindromic repeat; controlled study; Drosophila melanogaster; exercise; female; gene editing; genetically engineered mouse strain; heart muscle contractility; human; immunity; male; mast cell; motor performance; mouse; nonhuman; oxidation; skeletal muscle; vertebrate; animal; animal model; CRISPR Cas system; evolution; fitness; gene knock-in; genetics; metabolism; oxidation reduction reaction; phylogeny; physiology; point mutation; transgenic animal; vertebrate; Vertebrata; Aging; Animals; Animals, Genetically Modified; Biological Evolution; Calcium Signaling; Calcium-Calmodulin-Dependent Protein Kinase Type 2; CRISPR-Cas Systems; Drosophila melanogaster; Drosophila Proteins; Female; Gene Editing; Gene Knock-In Techniques; Male; Mice; Models, Animal; Oxidation-Reduction; Phylogeny; Physical Fitness; Point Mutation; Reactive Oxygen Species; Vertebrates
Type
journal article