# Emergence of a \"Cyclosome\" in a Primitive Network Capable of Building \"Infinite\" Proteins +
## 6 Conclusions  
To conclude, a small circular RNA, called AL, has been proposed with a sequence that has the following features:  
* Its subsequences (namely, pentamers) are observed as relics in many parts of modern genomes, especially in Archaea;
* AL relics are often present in \({}^{\text{t}}\)RNA loops, and in mitochondrial D-loops;
* An AL-heptamer constitutes the major part of the exon/intron boundary;
* A scalar proximity to AL explains the relationships between polymerases and, more generally, between complete genomes in phylogenetic trees of Archaea. This proximity suggests a common origin for these genomes.  
Hence, the AL cyclosome could have played the role of an ancient protein-synthesizing machine. This claim is central to the stereochemical hypothesis of the genetic code [115] and to the proposal by [PERSON] in 1973 [116]: The existence of catalytic RNAs in clays such as the \"montmorillonite\" may have facilitated the synthesis of small peptides and long RNAs (as is now done by synthetases, polymerases and replicases), thereby constituting an autocatalytic loop at the origin of life.  
Hairpin palindromic structure Hairpin size  
The existence of a simple RNA structure capable of surviving as a stable hairpin or functioning in a ring form was postulated soon after [PERSON]'s hypothesis [46; 47; 112], and numerous experimental  
Figure 11: (**a**) The GlytRNA\({}^{\text{GCC}}\) of _Lupine_[66]; (**b**) reconstruction of the loops of the GlytRNA\({}^{\text{GCC}}\) of _Lupine_ from four partial hairpins built from AL ring; (**c**) frequency histograms of bases in the anticodon loop of tRNAs belonging to the three domains of life [114].  
works [117; 118; 119] now reinforce this stereochemical hypothesis in a field that continues to advance both experimentally and theoretically.  
We anticipate six research developments will follow from the hypothesis presented here:  
* An attempt to take into account the potential evolutional path from the AL ring to the large ribosomal subunits (LSU) extracted from the modular organization of the rRNAs structure [17; 94; 120];
* A search for more AL relics in modern genomes at critical functional steps of the nuclear transcription/translation processes (notably when they are coupled as in Archaea [121], in which the Archaea \(\mathrm{tRNA^{Gly}}\) presents the following sequence in its three successive loops: TGGTA CTGCCA TTCAA, that is a 16-mer from AL [122]), mitochondrial energetic or cellular immune receptor machineries);
* An attempt to explain the evolution of tRNA secondary structures in relation to the genetic code [123; 124; 125; 126; 127; 128; 129; 130];
* An attempt to understand the evolution of immune systems (from CRISPR and TOLL to RAG systems [94; 95; 96; 97]), taking into account the reuse of former AL RNA fragments already present in the \"cyclosome\";
* The discovery of sequences linked to AL useful for synthetic biology and studies on \"minimal cell\" and its primitive genome, with original stable structures as those observed in the \"cyclosome\" (Figure 12);
* The identification of genetic networks based on common sequences inherited from AL and appearing in regulatory RNAs like microRNAs or circular RNAs.  
**Supplementary Materials:** The following are available online at [[http://www.mdpi.com/2075-1729/9/2/51/s1](http://www.mdpi.com/2075-1729/9/2/51/s1)]([http://www.mdpi.com/2075-1729/9/2/51/s1](http://www.mdpi.com/2075-1729/9/2/51/s1)).  
**Author Contributions:** Both authors contributed equally to the research described in the manuscript.  
Figure 12: The palindromic structure of the 25 rings. The couples or triplets of rings are obtained by exchanging the blue and the red subsequences.  
**Acknowledgments:** We are greatly indebted to [PERSON], [PERSON], [PERSON], [PERSON], and [PERSON] for many discussions about the molecular structures potentially involved at the origin of life.  
**Conflicts of Interest:** The authors declare that there is no conflict of interest regarding the publication of this paper.