Initial BlastP searches were performed at the National Center for Biotechnology Information site (http://www.ncbi.nlm.nih.gov/BLAST) in the non-redundant protein database (E < 0.001) using human and S. cerevisiae proteins as queries and E. coli AspRS for bacterial retrevals. BLAST parameters (Expect threshold and filtering options) were adapted if needed for short and/or biased sequences. The final set contains 184 sequences from which 40 fungi, 31 animals, 10 plants and 103 bacteria. The complete list of species is provided in the Supplementary Materials.
Sequences were then aligned using PipeAlign. The alignment was manually refined based on secondary structure and known Sequence Signature Motifs (SSMs). 
 The conservation profile was computed by averaging the pairwise sequence identities of a given sequence set inside a sliding window of 50 residues length. The score is assigned to the residues in the center of the window.