# Emergence of a \"Cyclosome\" in a Primitive Network Capable of Building \"Infinite\" Proteins +
## 4 Nucleo-Nucleic and Nucleo-Peptide Mechanisms
### Defence Mechanisms  
The CRISPR-CAS system provides bacteria like _Streptococcus agalactiae_ with adaptive immunity and the AL-pentamers ATGGT and ATTCA, and AL-hexamers AATGGT and TCAAGAT (corresponding respectively to the D-loop and T\(\Downarrow\)-loop of many \({}^{\mathrm{t}}\)RNAs) are often found at many levels of the system (CAS proteins, Casposon TIR and CRISP repeats [94]), e.g., typical repeat sequences for CRISPR1 and CRISPR3 [95] contain AL-heptamers shared by AL and tRNA loops:  
GTTTTGTACTCTCAAGATTTAAAGTAACTGTACAAC (CRISPR1)  
GTTTTAGAGCTGTGTTTCGATATGGTTCCAAAAC (CRISPR3),  
as well as the sequences of TIR and CRISPR compared in [96; 97], a consensus sequence from central part of the murine RSS VxL8, JB2.6, and JB2.2 [98; 99; 100], and human RSS spacer common for Vh, V328h2, and V328 [101; 102; 103] described in Table 6 and also the protein H354 of Mimivirus kasai [104] (see Supplementary Material 3 for calculations of AL-proximity CRISPR-CAS proteins).  
The probabilities of a match between the AL and sequences of elements involved in defence mechanisms, at different levels of evolution, are the following:  
p = 2.10\({}^{-9}\) for 19 matches (with an insertion) between TIR and CRISPR using the binomial distribution B(1/4,22), p = 8.10\({}^{-6}\) for 15 anti-matches between AL and CRISPR plus 1 quasi-anti-match G-T using the distribution B(1/4,21) \(\times\) B(3/8,1),  
\begin{table}
\begin{tabular}{|l|} \hline \(3\)’-ATACATCC(C)TCTTAAGTTCCCTT-5’ (TIR) \\ \hline \(3\)’-TTCCATCC -TCTTAAGTTCGATT-5’ (CRISPR) \\ \hline \(5\)’-ATGGTACTAG - CCATTCAAGATG-3’ (AL) \\ \hline \(5\)’-GTGATACAG - CCCTTAACAAAA-3’ (murine consensus RSS) \\ \hline \(5\)’-ATTCAAACATGAA-3’ (human RSS spacer) \\ \hline \end{tabular}
\end{table}
Table 6: Sequences of elements involved in defence mechanisms compared to AL.  
\begin{table}
\begin{tabular}{|l|} \hline TCAATCAAGATGAAAGGTACGT tRNA synthetase CCMP1335 XM_002286706.1 **2.73** \\ \hline AGAGTCAAAGATGAATAGTAGTA glvcyclt-tRNA synthetase CCMP1335 XM_002286964.1 **2.44** \\ \hline CCATGCAAGATGATGGGTG glvcyclt-tRNA synthetase CCMP1335 XM_002288084.1 **1.92** \\ \hline GCATTCAAGATGAACTCTTG **arginyl-tRNA synthetase CCMP1335 XM_002288460.1 **2.19** \\ \hline TCCATCTCATGGAATGATG methodi-tRNA synthetase CCMP1335 XM_002292549.1 **1.91** \\ \hline CTACCTGATGAAAGGTCATG vallylt-tRNA synthetase CCMP1335 XM_002295439.1 **2.32** \\ \hline GCATACAAGAGAGATGATGATG cystinylt-tRNA synthetase CCMP1335 XM_002286789.1 **2.04** \\ \hline CCATTCGAAATGTTGGATATG tRNA-Gly mitochondrion DQ186202.1 **7.14** \\ \hline CCATGTGTTGATGAAAC 605 ribosomal protein CCMP1335 XM_002290416.1 **1.83** \\ \hline CCAAGGAG\(\mathrm{p}=7.10^{-4}\) for 13 matches between AL and consensus RSS using the binomial distribution B(1/4,22), \(\mathrm{p}=2.10^{-6}\) for 11 matches between AL and RSS spacer using the binomial distribution B(1/4,12).  
In Mimivirus, a mechanism similar to CRISPR has been discovered [104], which involves two exonucleases R 350 and R 354 having respectively 3.02 and 3.71 as the values of the AL-proximity:  
* Acanthamoeba castellani mimivirus DNA, nearly complete genome, strain: Mimivirus kasaii GenBank: AP017644.1 457483-459936 R 350 Lambda-type exonuclease, with AL-proximity **3.02**;
* Acanthamoeba castellani mimivirus DNA, nearly complete genome, strain: Mimivirus kasaii GenBank: AP017644.1 462878-464527 R 354 Lambda-type exonuclease, with AL-proximity **3.71**. Moreover, the sequences of the genes of these exonucleases contain numerous heptamers like: \(5^{\prime}\)**-GATGAGAATGATGAAAGAT-\(3^{\prime}\)** (MIMIVIRE gene H354).