The Conservation Of Lysine Acetylation From Mouse To Human

Each and every one of the cellular processes requires the use of proteins. To enable plasticity in response to different stimuli, those proteins should have several regulatory layers, one of which is the attachment of posttranslational modifications – PTMs.

Lysine acetylation is a common, highly reversible PTM found in all life forms. There is a large variety of acetylated proteins, including histones, transcription factors, chaperones and many more. Acetylation sites on those key proteins tend to be evolutionary conserved. Yet, in spite of its clear significance in maintaining physiological and molecular homeostasis, the effect of protein acetylation is not fully understood.

Here we present an examination of the conservation level of lysine residues vs. the conservation of acetylated lysine residues in orthologous proteins between mouse and human. We have found that while only 76% of lysines are conserved between the proteomes, there is a 92% conservation of acetylated lysines. Moreover, pathway analysis of the acetylated proteins shows a common attribute – the effect on key processes in the cell, like fatty acid and energy metabolism, inflammation, one carbon cycle and more. Furthermore, pathway analysis of the 8% of proteins that lost their acetylation during evolution also show key pathways like fatty acid and energy metabolism, neurodegenerative diseases, etc. Our results open a door for research of the evolution of acetylation and its importance in guiding key processes and evolutionary-related changes between organisms.