**1. Introduction**

Mitochondrial genetic code diversification frequently reassigns stop codons to amino acids [1]. This situation probably reflects ambiguity in roles of stop codons during translation in mitochondria. Indeed, phylogenetic reconstructions of the evolution of genetic codes based on differences between codons in amino acid and stop codon assignments resemble known phylogenies of organisms using these genetic codes, if ambiguity of stop codons in mitochondrial (but not nuclear) genetic codes is accounted [2].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

These observations suggest translational activity of mitochondrial tRNAs with anticodons matching stop codons [3] templated by antisense strands of regular mitochondrial tRNAs [4, 5]. Predicted occurrences of mitochondrial stop suppressor (antiterminator) tRNAs coevolve with stop codon usages in predicted off-frame protein coding genes in all analyzed mitochondria (primates and Drosophila [6, 7], including their ribosomal RNAs [8], turtles [9] and Chaetognaths [10]), and in a peptide detected by specific monoclonal immunolocalization in human mitochondria [11]. Hence, there are probably more mitochondrion-encoded genes than usually accepted [12, 13]. Mitogenome size reduction probably causes gene multifunctionality, including mt tDNAs functioning as replication origins [14–21].

is frequently used as shortcut for inverse complement, but the A<>T + C<>G transformed sequence is a different sequence because it lacks the 3′-to-5′ inversion combined with nucleotide complementarity. The shortcut has been used because 3′-to-5′ inverted sequences had not

Directed Mutations Recode Mitochondrial Genes: From Regular to Stopless Genetic Codes

http://dx.doi.org/10.5772/intechopen.80871

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It seems regular transcription occasionally switches abruptly to swinger transcription (and vice versa), as indicated by chimeric RNAs. These RNAs correspond in part to regular DNA, and an adjacent part corresponds to DNA only if accounting for swinger transformation [62]. Corresponding chimeric peptides have also been detected [63]. Chimeric DNA also exists: the mitogenome of the stonefly *Kamimuria wangi* (NC\_024033) is regular, beside its 16S rRNA,

Secondary structures are important components of RNA function and evolution [64, 65]. Secondary structures formed by tRNA sequences punctuate posttranscriptional processing of mitochondrial transcripts [66–68]. Palindromes potentially forming secondary structures after sequence swinger-tranformation associate with detected mitochondrial swinger RNAs [69]. This is similar to what is known from regular RNA processing in mitochondria and, surprisingly, giant viruses [70] which bear also other striking resemblances with mitogenomes, including similar gene order [71]. Transcription sometimes deletes systematically mono- or dinucleotides after transcribing trinucleotides (del-transcription), translated into peptides that in part converge with peptides translated from regular RNAs by expanded anticodons [38]. Del-transcription, or at least detection of delRNAs, seems downregulated by secondary structures formed after transformation of the sequence by systematic dele-

Phenomena systematically exchanging nucleotides remind more specific mechanisms that alter the genetic code according to which a protein is coded, from a regular genetic code to a stopless genetic code, and/or vice versa. Indeed, previous analyses of mitogenomes revealed that in one GenBank mitogenome (from a marine turtle, the Olive Ridley, *Lepidochelys olivacea*), following GenBank's annotations, several regular protein coding genes do not code for the regular proteins essential for mitochondrial metabolism and usually encoded at these genomic locations. These essential proteins are indeed coded by the corresponding sequences, but only after a frameshift, and only if stops in that frame are translated, explaining the erroneous annotation of stopless ORFs (abbreviation for open reading frames) that do not code for

This was originally interpreted as resulting from directed selection on stop codons. Observations of systematic mutations in contexts creating stop codons in ORFs of HIV genes specifically in elite controllers immune to HIV [73, 74] suggests that enzymatically directed mutagenesis during DNA replication and/or edition could transform ORFs coded according to a regular genetic code into one coded by a stopless genetic code, and vice versa, as observed in several mitochondrial genes of the Olive Ridley. For HIV, introducing stops presumably

been described previous to the description of A<>T + C<>G transformed sequences.

which is entirely swinger transformed along transformation A<>T + C<>G [46].

**1.3. Regulation of alternative transcriptions by secondary structure**

**1.4. Mechanisms that switch between genetic codes?**

drastically reduces viral production and contributes to immunity.

recognized mitochondrial proteins [9].

tions [72].

Translation of stop codons occurs in different organisms [22, 23], but seems particularly widespread in mitochondria [2, 3] as reflected by the evolution of mitochondrial genetic codes [1]. Nuclear genetic codes lacking dedicated stop codons have been described in protists [24–27] and fungi [28].
