CaMKII oxidation is a critical performance/disease trade-off acquired at the dawn of vertebrate evolution

Qinchuan Wang, Erick O. Hernández-Ochoa, Meera C. Viswanathan, Ian D. Blum, Danh C. Do, Jonathan M. Granger, Kevin R. Murphy, An Chi Wei, Susan Aja, Naili Liu, Corina M. Antonescu, Liliana D. Florea, C. Conover Talbot, David Mohr, Kathryn R. Wagner, Sergi Regot, Richard M. Lovering, Peisong Gao, Mario A. Bianchet, Mark N. WuAnthony Cammarato, Martin F. Schneider, Gabriel S. Bever, Mark E. Anderson

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number3175
JournalNature communications
Issue number1
StatePublished - Dec 1 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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