Citric acid cycle and the origin of MARS

Abstract

The vertebrate multiaminoacyl tRNA synthetase complex (MARS) is an assemblage of nine aminoacyl tRNA synthetases (ARSs) and three non-synthetase scaffold proteins, aminoacyl tRNA synthetase complex-interacting multifunctional protein (AIMP)1, AIMP2, and AIMP3. The evolutionary origin of the MARS is unclear, as is the significance of the inclusion of only nine of 20 tRNA synthetases. Eight of the nine amino acids corresponding to ARSs of the MARS are derived from two citric acid cycle intermediates, α-ketoglutatrate and oxaloacetate. We propose that the metabolic link with the citric acid cycle, the appearance of scaffolding proteins AIMP2 and AIMP3, and the subsequent disappearance of the glyoxylate cycle, together facilitated the origin of the MARS in a common ancestor of metazoans and choanoflagellates.

Figure 1

Amino acid biosynthetic pathways. Nineteen of the twenty amino acids (rounded rectangles) are synthesized directly or indirectly from the metabolites of glycolysis (nine) and the citric acid cycle (ten) (pathways separated by dashed horizontal line). Amino acids whose corresponding ARSs are components of the MARS are highlighted (gray background). Key components of glyoxylate cycle are shown (arrows with dashed lines). The citric acid cycle takes place in the mitochondria, whereas glycolysis and MARS are localized in the cytoplasm.

Figure 2

The origin of the MARS and other multi-ARS complexes. Tree of life with key branch points is shown (with example organisms in parentheses). The appearance and disappearance of AIMP1, 2, and 3, the glyoxylate cycle, and multi-ARS complexes are indicated (arrows); possible early origin of MARS is shown by dashed line. The presence or absence of AIMP2, AIMP3, isocitrate lyase, malate synthase (the latter two are glyoxylate cycle-specific enzymes) was determined using NCBI database and Origins of Multicellularity database of the Broad institute.