Why methionine as the initiating amino acid?Production of methioninein the supposed prebiotic chemistry conditions, present no particularchallenges (Kim andBenner, 2018) .
Methionine could be initially incorporated into the primordialRNA-dependent world as a cofactor because, among others, of its involvement inmethyltransferase activities although spontaneous emergence of S-Adenosylmethioninein the RNA world is very conceivable (Laurino and Tawfik, 2017) .In addition, thiol-richpeptides can play various catalytic roles (Vallée et al., 2017) and compounds with sulfur and thioesters must have played a crucial role inthe origin of amino acid activation and peptide bond synthesis (Jakubowski, 2016) . Furthermore, methionine preferentially interactswith its codon AUG (Mellersh,1993) . Therefore,several studies, not all mentioned here, suggest that methionine and its thiolatedprecursor and derivativemolecules would have rapidly interacted with RNAs and play critical roles inthe RNA world to the RNA/protein world transition.On the other hand,if one extrapolates data from current biological systems to proto-cell world,various data suggest that it should be very advantageous to initiate thesynthesis of proteins with a methionine. For many proteins, the identity ofthe first residue that remains after removal of the NH2-terminalmethionine residue has a profound influence on half-life.
This is called the N-end rule. Even if it hasdifferences according to the type of proteins and the organisms, methionine isone of the few amino acids that can significantly increase the half-life ofproteins (Varshavsky, 1995) . In current organisms, the rapid removalof initial methionine allows an increased protein turnover that is an adaptivemechanism, but in the distant past, it could be very advantageous for theproteins (or only peptides) to remain functional for very long periods and thusto retain the initiating amino acid. This could also be correlated to the relativelyhigh biologic half-life of methionine. Moreover, the metabolic cost of methionine synthesis ishighest among the amino acids (Kaleta et al., 2013) ; so, initiating synthesis by this amino acid almost ensuringthat the risk of deficiencies in other amino acids and energy intermediarieswas low.Already in the RNAworld, the interactions with methionine could have to be numerous, moreover,the advantage that would be obtained by the integration of this amino acid asthe first residue during the synthesis of the proteins is such that a codonstart coding for this amino acid (or a modified version as N-formylmethionine) mighthave appeared very early in the course of evolution.
In prebiotic conditions,selection largely depended on the stability of the molecules. The cloverleaftRNAs and the rRNAs (constituting the proto-PTC and moreover being able toderive from tRNA fusion) are very stable molecules (Megel et al.,2015) . A mRNA in the form of ss-tRNA or a combination of severalof these last molecules would have been weakly fragile. In the supposedly conditionsof the prebiotic world, methionine could be protected from degradation by, inpart, interacting with the RNA, and under standard conditions of life, itproved to be a relatively stable molecule and which moreover can stabilize theproteins when it is the first incorporated residue and also the second.
Theorigin of codons of initiation attributed to methionine is thus very old and their presences at thefirst stages of the RNA/protein world and in some proto-tRNAs can not beexcluded.