Metabolic origin of the fused aminoacyl-tRNA synthetase, glutamyl-prolyl-tRNA synthetase

About 1 billion years ago, in a single-celled holozoan ancestor of all animals, a gene fusion of two tRNA synthetases formed the bifunctional enzyme, glutamyl-prolyl-tRNA synthetase (EPRS). We propose here that a confluence of metabolic, biochemical, and environmental factors contributed to the spec...

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Bibliographic Details
Published in:The Journal of biological chemistry 2018-12, Vol.293 (49), p.19148-19156
Main Authors: Eswarappa, Sandeep M., Potdar, Alka A., Sahoo, Sarthak, Sankar, Santhosh, Fox, Paul L.
Format: Article
Language:English
Subjects:
Amino Acyl-tRNA Synthetases - chemistry
Amino Acyl-tRNA Synthetases - genetics
Amino Acyl-tRNA Synthetases - metabolism
Animals
Bacteria - genetics
Bacterial Proteins - chemistry
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Citric Acid Cycle
Editors' Picks
Evolution, Molecular
Gene Fusion
Glutamate-tRNA Ligase - chemistry
Glutamate-tRNA Ligase - genetics
Glutamate-tRNA Ligase - metabolism
Glutamic Acid - chemistry
Glutamic Acid - metabolism
Ketoglutaric Acids - chemistry
Ketoglutaric Acids - metabolism
Models, Chemical
Proline - chemistry
Proline - metabolism
Protein Biosynthesis - genetics
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Summary:About 1 billion years ago, in a single-celled holozoan ancestor of all animals, a gene fusion of two tRNA synthetases formed the bifunctional enzyme, glutamyl-prolyl-tRNA synthetase (EPRS). We propose here that a confluence of metabolic, biochemical, and environmental factors contributed to the specific fusion of glutamyl- (ERS) and prolyl- (PRS) tRNA synthetases. To test this idea, we developed a mathematical model that centers on the precursor–product relationship of glutamic acid and proline, as well as metabolic constraints on free glutamic acid availability near the time of the fusion event. Our findings indicate that proline content increased in the proteome during the emergence of animals, thereby increasing demand for free proline. Together, these constraints contributed to a marked cellular depletion of glutamic acid and its products, with potentially catastrophic consequences. In response, an ancient organism invented an elegant solution in which genes encoding ERS and PRS fused to form EPRS, forcing coexpression of the two enzymes and preventing lethal dysregulation. The substantial evolutionary advantage of this coregulatory mechanism is evidenced by the persistence of EPRS in nearly all extant animals.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.RA118.004276