**2. Materials and methods**

codons [2–8] by tRNAs with anticodons matching stops [9–11] or by tRNAs with expanded anticodons [12–14]. Assuming fusion of different transcripts explains the origins of some of these non-canonical RNAs [15]. Some human RNAs matching exons differ from their DNA by specific changes, called RDDs (RNA-DNA differences) [16]. RDDs can be single nucleotide substitutions or deletions [17–19], presumably resulting from post-transcriptional edition [20, 21]. Some short transcripts correspond to mitochondrial DNA at the condition that one assumes mono- or dinucleotide deletions after each transcribed nucleotide triplet [22, 23]. Formation of secondary structures by del-transformed sequences apparently downregulates

Another type of systematic transformation consists of 23 systematic exchanges between nucleotides, 9 symmetric (X ↔ Y, e.g. A ↔ C,) [25, 26] and 14 asymmetric exchanges (X → Y → Z → X, e.g. A → C → G → A) [26, 27]. For example, in systematic transformation A ↔ C, nucleotide A is introduced in place of nucleotide C and vice versa. The two-headed arrow (↔) indicates that A and C replace each other during transcription. One-headed arrows (→) indicate asymmetric exchanges: in the example A → C → G → A, nucleotide A is systematically incorporated in place of every C; similarly, C replaces G and G replaces A during RNA polymerisation. Transcripts corresponding to systematic exchanges are called swinger RNAs. BLASTn analyses detect about 100 predicted swinger RNAs (longer than 100 nucleotides) in GenBank's EST database in addition to the (approximately) 10,000 canonical human mitochondrial RNAs in that database. Hence, about 1% of the human mitochondrial transcripts in GenBank's EST database correspond to 1 among 23 systematic nucleotide exchanges [25–28]. These systematic nucleotide exchanges (an expression that fits chemical contexts) are called bijective transformations in mathematical contexts [29–31]; swinger transcription fits

Mitogenomes are comparatively small, also because of the selection against multiple direct repeats [32–35] and invert repeats [15]: these form secondary structures that are frequently excised; such deletions are frequently deleterious. Vertebrate mitogenomes have densely packed coding and non-coding regions templating for RNAs. Non-canonical transformations greatly increase potential numbers of RNA products for single sequences: four and five RNA transcripts when assuming systematic deletions of mono- and dinucleotides for deltranscriptions, respectively, and 23 swinger RNAs when considering systematic nucleotide exchanges. Therefore, studies of swinger transformations focus on the human mitogenome, which is short (16,569 bp), hence reducing potential false-positive detections due to sheer genome size and because ample sequence data are available from several sources for this

Note that swinger DNA has been detected (mainly corresponding to rRNA genes) for mitochondrial and nuclear sequences [36–38]. Hence, swinger RNAs result from canonical transcription of swinger-transformed DNA or swinger transcription of regular DNA [22]. Some mass spectra match predicted peptides translated from del- and swinger-transformed RNA [39–42]. Detection of chimeric RNAs, consisting of part regular, and part swinger-transformed contiguous sequences suggests that regular canonical and swinger-transformed RNA result

del-transcription itself or its products, delRNAs [24].

biological contexts.

80 Mitochondrial DNA - New Insights

organism.
