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 Jr; David Mohr; Kathryn R Wagner; Sergi Regot; Richard M Lovering; Peisong Gao; Mario A Bianchet; Mark N Wu; Anthony Cammarato; Martin F Schneider; Gabriel S Bever; Mark E Anderson

doi:10.1038/s41467-021-23549-3

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

Nat Commun. 2021 May 26;12(1):3175. doi: 10.1038/s41467-021-23549-3.

Authors

Qinchuan Wang¹, Erick O Hernández-Ochoa², Meera C Viswanathan³, Ian D Blum⁴, Danh C Do³, Jonathan M Granger³, Kevin R Murphy³, An-Chi Wei⁵, Susan Aja^{6

7}, Naili Liu⁸, Corina M Antonescu⁹, Liliana D Florea⁹, C Conover Talbot Jr¹⁰, David Mohr¹¹, Kathryn R Wagner^{4

8}, Sergi Regot¹², Richard M Lovering¹³, Peisong Gao³, Mario A Bianchet^{4

14}, Mark N Wu⁴, Anthony Cammarato³, Martin F Schneider², Gabriel S Bever^{3

15}, Mark E Anderson¹⁶

Affiliations

¹ Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. qinchuan.wang@jhmi.edu.
² Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.
³ Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁴ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁵ Department of Electrical Engineering, Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
⁶ Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁷ Center for Metabolism and Obesity Research, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁸ Center for Genetic Muscle Disorders, Kennedy Krieger Institute, Baltimore, MD, USA.
⁹ Johns Hopkins Computational Biology Consulting Core, Baltimore, MD, USA.
¹⁰ Institute for Basic Biomedical Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹¹ Johns Hopkins School of Medicine Genetic Resources Core Facility, Baltimore, MD, USA.
¹² Department of Molecular Biology & Genetics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹³ Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, USA.
¹⁴ Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, MD, USA.
¹⁵ Center for Functional Anatomy & Evolution, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹⁶ Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. mark.anderson@jhmi.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aging / physiology*
Animals
Animals, Genetically Modified
Biological Evolution*
CRISPR-Cas Systems / genetics
Calcium Signaling / physiology
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
Drosophila Proteins / genetics
Drosophila Proteins / metabolism
Drosophila melanogaster
Female
Gene Editing
Gene Knock-In Techniques
Male
Mice
Models, Animal
Oxidation-Reduction
Phylogeny
Physical Fitness / physiology
Point Mutation
Reactive Oxygen Species / metabolism*
Vertebrates / physiology*

Substances

Drosophila Proteins
Reactive Oxygen Species
Calcium-Calmodulin-Dependent Protein Kinase Type 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding