Mutation Patterns Due to Converging Mitochondrial Replication and Transcription Increase Lifespan, and Cause Growth Rate-Longevity Tradeoffs

Seligmann, Hervé

doi:10.5772/24319

Cited by 20 publications

(18 citation statements)

References 117 publications

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“…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][15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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

Seligmann¹

2018

Mitochondrial DNA - New Insights

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Mitochondrial genetic codes evolve as side effects of stop codon ambiguity: suppressor tRNAs with anticodons translating stops transform genetic codes to stopless genetic codes. This produces peptides from frames other than regular ORFs, potentially increasing protein numbers coded by single sequences. Previous descriptions of marine turtle Olive Ridley mitogenomes imply directed stop-depletion of noncoding +1 gene frames, stop-creation recodes regular ORFs to stopless genetic codes. In this analysis, directed stop codon depletion in usually noncoding gene frames of the spiraling whitefly Aleurodicus dispersusʼ mitogenome produces new ORFs, introduces stops in regular ORFs, and apparently increases coding redundancy between different gene frames. Directed stop codon mutations switch between peptides coded by regular and stopless genetic codes. This process seems opposite to directed stop creation in HIV ORFs within genomes of immunized elite HIV controllers. Unknown DNA replication/edition mechanisms probably direct stop creation/depletion beyond natural selection on stops. Switches between genetic codes regulate translation of different gene frames.

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Section: Introductionmentioning

confidence: 99%

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

Seligmann¹

2018

Mitochondrial DNA - New Insights

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“…In human mitochondria, stem-loop DNA structures define replication origins (Hixson et al, 1986; Clayton, 1992, 2000; Seligmann and Krishnan, 2006; Seligmann et al, 2006a,b; Seligmann, 2008, 2010a, 2011; Seligmann and Labra, 2014). They guide RNA processing in mitochondria (Ojala et al, 1981), and in giant viruses and their virophages (Byrne et al, 2009; Claverie and Abergel, 2009).…”

Section: Introductionmentioning

confidence: 99%

Evolution of Nucleotide Punctuation Marks: From Structural to Linear Signals

Houmami

Seligmann

2017

Front. Genet.

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We present an evolutionary hypothesis assuming that signals marking nucleotide synthesis (DNA replication and RNA transcription) evolved from multi- to unidimensional structures, and were carried over from transcription to translation. This evolutionary scenario presumes that signals combining secondary and primary nucleotide structures are evolutionary transitions. Mitochondrial replication initiation fits this scenario. Some observations reported in the literature corroborate that several signals for nucleotide synthesis function in translation, and vice versa. (a) Polymerase-induced frameshift mutations occur preferentially at translational termination signals (nucleotide deletion is interpreted as termination of nucleotide polymerization, paralleling the role of stop codons in translation). (b) Stem-loop hairpin presence/absence modulates codon-amino acid assignments, showing that translational signals sometimes combine primary and secondary nucleotide structures (here codon and stem-loop). (c) Homopolymer nucleotide triplets (AAA, CCC, GGG, TTT) cause transcriptional and ribosomal frameshifts. Here we find in recently described human mitochondrial RNAs that systematically lack mono-, dinucleotides after each trinucleotide (delRNAs) that delRNA triplets include 2x more homopolymers than mitogenome regions not covered by delRNA. Further analyses of delRNAs show that the natural circular code X (a little-known group of 20 translational signals enabling ribosomal frame retrieval consisting of 20 codons {AAC, AAT, ACC, ATC, ATT, CAG, CTC, CTG, GAA, GAC, GAG, GAT, GCC, GGC, GGT, GTA, GTC, GTT, TAC, TTC} universally overrepresented in coding versus other frames of gene sequences), regulates frameshift in transcription and translation. This dual transcription and translation role confirms for X the hypothesis that translational signals were carried over from transcriptional signals.

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“…Natural genomes are frequently characterized by gradients in nucleotide biases, proportional to times spent single stranded during replication. This is typically due to hydrolytic deaminations, resulting in the observed nucleotide bias gradients across genomes due to replication [33][34][35][36][37] and/or to transcription [38,39]. Some evidences suggest that deamination gradients do not always result from chemical changes, but from coding constraints that locate genes with high deamination risks at positions where these risks are low (i.e., close to replication/transcription origin(s)) and the genes with nucleotide contents that imply lower deamination risks at locations with higher deamination risks, i.e., at genomic locations that are distant from replication/transcription origins [36,40].…”

Section: Replication Origins and Rna Ringsmentioning

confidence: 99%

The primordial tRNA acceptor stem code from theoretical minimal RNA ring clusters

Demongeot

Seligmann

2020

BMC Genet

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Background: Theoretical minimal RNA rings code by design over the shortest length once for each of the 20 amino acids, a start and a stop codon, and form stem-loop hairpins. This defines at most 25 RNA rings of 22 nucleotides. As a group, RNA rings mimick numerous prebiotic and early life biomolecular properties: tRNAs, deamination gradients and replication origins, emergence of codon preferences for the natural circular code, and contents of early protein coding genes. These properties result from the RNA ring's in silico design, based mainly on coding nonredundancy among overlapping translation frames, as the genetic code's codon-amino acid assignments determine. RNA rings resemble ancestral tRNAs, defining RNA ring anticodons and corresponding cognate amino acids. Surprisingly, all examined RNA ring properties coevolve with genetic code integration ranks of RNA ring cognates, as if RNA rings mimick prebiotic and early life evolution. Methods: Distances between RNA rings were calculated using different evolutionary models. Associations between these distances and genetic code evolutionary hypotheses detect evolutionary models best describing RNA ring diversification. Results: Here pseudo-phylogenetic analyses of RNA rings produce clusters corresponding to the primordial code in tRNA acceptor stems, more so when substitution matrices from neutrally evolving pseudogenes are used rather than from functional protein coding genes reflecting selection for conserving amino acid properties. Conclusions: Results indicate RNA rings with recent cognates evolved from those with early cognates. Hence RNA rings, as designed by the genetic code's structure, simulate tRNA stem evolution and prebiotic history along neutral chemistry-driven mutation regimes.

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Mutation Patterns Due to Converging Mitochondrial Replication and Transcription Increase Lifespan, and Cause Growth Rate-Longevity Tradeoffs

Cited by 20 publications

References 117 publications

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

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

Evolution of Nucleotide Punctuation Marks: From Structural to Linear Signals

The primordial tRNA acceptor stem code from theoretical minimal RNA ring clusters

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