Preface

Chapter 7 **Phylogenetic Evolution and Phylogeography of Tibetan Sheep**

Jianbin Liu, Xuezhi Ding, Yufeng Zeng, Xian Guo, Xiaoping Sun and

**Based on mtDNA D-Loop Sequences 135**

**Section 3 The Human Mitogenome in Health and Disease 153**

Chapter 8 **Mitochondrial Aging and Metabolism: The Importance of a**

Mónica Ríos-Silva and Blanca Torres-Mendoza

Chapter 10 **Mitochondrial DNA Variations in Tumors: Drivers or**

Edoardo Errichiello and Tiziana Venesio

**for Cancer Therapy 179**

Villota and Luis O. Burzio

**Passengers? 195**

Chapter 9 **Long Noncoding Mitochondrial RNAs (LncmtRNAs) as Targets**

Jaime Villegas Olavarria, Verónica A. Burzio, Vincenzo Borgna, Lorena Lobos-Gonzalez, Mariela Araya, Francisca Guevara, Claudio

**Good Relationship in the Central Nervous System 155** Genaro Gabriel Ortiz, Mario A Mireles-Ramírez, Héctor González-Usigli, Miguel A Macías-Islas, Oscar K Bitzer-Quintero, Erandis Dheni Torres-Sánchez, Angélica L Sánchez-López, Javier Ramírez-Jirano,

Chao Yuan

**VI** Contents

The mitochondrial genome has always been the stepchild of modern molecular biology, per‐ haps because it is falsely considered as a quantitatively negligible curiosity. However, mito‐ genomes are probably at the crossroads of molecular biology and evolution. Mitogenomes, under constraints for size reduction, probably reflect the origin of life and its primordial coding systems by multiplying various types of sequence multifunctionalities. The evolution of mitochondrial genetic codes and the apparent use of different translation and transcrip‐ tion rules are notable examples. Notably, mitochondrial tRNAs differ from other tRNAs, pu‐ tatively suggesting independent origins of mitochondrial tRNAs when translation evolved from transcription.

Recent phylogenetic analyses of mitochondrial proteomes also suggest that mitogenomes are an independent branch of the tree of life. Indeed, mitogenomes use an elusive non-com‐ plementary circular code that differs from the otherwise near universal self-complementary circular code used in most pro- and eukaryotes to regulate the ribosomal translation frame, as circular code motifs are conserved in tRNAs and rRNAs. This might reflect that mitoge‐ nomes are rare exceptions to Chargaff's rule that complementary nucleotides have approxi‐ mately equal frequencies on any long enough single-stranded DNA or RNA sequence, evaded by single stranded genomes and organellar genomes, including mitogenomes. For mitogenomes, this is probably due to strand asymmetric replication that causes directional mutation gradients in nucleotide contents along the genome, according to distances from heavy and light strand replication (and transcription) origins.

Until additional independent evidence is found, we stick to the accepted view that mito‐ chondria are ultrasymbiontic alphaproteobacteria. Nevertheless, the ancestral synteny ob‐ served between amoeban mitogenomes and genomes of their parasites, the giant viruses, could fit the view that mitochondria are an independent lineage, and/or that giant viruses developed from hypothetical, rare endospore-like structures formed by stressed mitochon‐ dria or their proteobacterial ancestor while switching cellular hosts. Indeed, giant viruses might be an independent, though controversial, fourth major lineage of life. Another point that mitochondria teach us in relation to the origins of life relates to the main axis of RNA evolution, from tRNA-like to rRNA-like. Several alignments and structural evidence suggest that tRNA accretions formed rRNAs, and in particular the ribosomal translational core. Mi‐ tochondrial ribosomes include, instead of a 5S rRNA subunit, a structural element consisting of an otherwise regular tRNA.

This short compilation of chapters on mitogenomes reflects the importance of mitogenomes to some extents in relation to molecular biology (chapters 1-4) as a tool in population genet‐ ics and reconstructing recent evolution (chapters 5-7), and also in the management of eco‐ nomically important populations, including humans (chapters 8-10).

Mitogenomes prepare more surprises such as this example perhaps even unexpected to some authors of chapters in this book: some eukaryota lack mitochondria. Mitochondria will continue to open our minds.

> **Hervé Seligmann** The Natural History Collections The Hebrew University of Jerusalem Jerusalem, Israel

Marseille, Bouches-du-Rhône, Provence-Alpes-Côte d'Azur, France

**Ganesh Warthi**

**Molecular Biology**

**Section 1**

Aix-Marseille University

**Section 1**

**Molecular Biology**

ics and reconstructing recent evolution (chapters 5-7), and also in the management of eco‐

Mitogenomes prepare more surprises such as this example perhaps even unexpected to some authors of chapters in this book: some eukaryota lack mitochondria. Mitochondria will

Marseille, Bouches-du-Rhône, Provence-Alpes-Côte d'Azur, France

**Hervé Seligmann**

Jerusalem, Israel **Ganesh Warthi**

Aix-Marseille University

The Natural History Collections The Hebrew University of Jerusalem

nomically important populations, including humans (chapters 8-10).

continue to open our minds.

VIII Preface

**Chapter 1**

**Provisional chapter**

**True Mitochondrial tRNA Punctuation and Initiation**

**True Mitochondrial tRNA Punctuation and Initiation** 

DOI: 10.5772/intechopen.75555

**Using Overlapping Stop and Start Codons at Specific**

**Using Overlapping Stop and Start Codons at Specific** 

In all the taxa and genomic systems, numerous *trn* genes (specifying tRNA) exhibit at specific conserved positions nucleotide triplets corresponding to stop codons (TAG/TAA). Similarly, relatively high frequencies of start codons (ATG/ATA) occur in fungi/metazoan mitochondrial-*trn* genes. The last nucleotide of these triplets is the first involved in the 5′-Dor 5′-T-stem, respectively. Their frequencies are tRNA species dependent. The products of these genes which bear one or two types of these codons are called ss-tRNAs (for stop/start). Metazoan mt-genomes are generally very compact, and many same strand overlapping sequences may simultaneously code for tRNAs and mRNAs. However, this study suggests that overlaps are not a direct mechanism to substantially reduce genome size. For proteinencoding genes, occulting possible overlaps, there are only alternative start codons and/or truncated stop codons, but the first putative in-frame standard initiation codon or complete stop codon is in the upstream or downstream overlapping ss-*trn* sequences, respectively. Even if, to date, experimental data are missing, stress signals might regulate producing extended or not proteins. Finally, possible implications of tRNA/mRNA hybrid molecules

in the "RNA world" to "RNA/protein world" transition will be discussed.

**Keywords:** mitochondrion, tRNA origin, start codon, stop codon, overlap, origin of life,

Transfer RNAs are key partners in the ribosome-translation machinery. Generally, they are composed of c.70–90 nucleotides (nts). Moreover, they are the most abundant nucleic acid

> © 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.

**and Conserved Positions**

**and Conserved Positions**

Eric Faure and Roxane Barthélémy

Eric Faure and Roxane Barthélémy

http://dx.doi.org/10.5772/intechopen.75555

**Abstract**

RNA world

**1. Introduction**

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

#### **True Mitochondrial tRNA Punctuation and Initiation Using Overlapping Stop and Start Codons at Specific and Conserved Positions True Mitochondrial tRNA Punctuation and Initiation Using Overlapping Stop and Start Codons at Specific and Conserved Positions**

DOI: 10.5772/intechopen.75555

Eric Faure and Roxane Barthélémy Eric Faure and Roxane Barthélémy

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.75555

#### **Abstract**

In all the taxa and genomic systems, numerous *trn* genes (specifying tRNA) exhibit at specific conserved positions nucleotide triplets corresponding to stop codons (TAG/TAA). Similarly, relatively high frequencies of start codons (ATG/ATA) occur in fungi/metazoan mitochondrial-*trn* genes. The last nucleotide of these triplets is the first involved in the 5′-Dor 5′-T-stem, respectively. Their frequencies are tRNA species dependent. The products of these genes which bear one or two types of these codons are called ss-tRNAs (for stop/start). Metazoan mt-genomes are generally very compact, and many same strand overlapping sequences may simultaneously code for tRNAs and mRNAs. However, this study suggests that overlaps are not a direct mechanism to substantially reduce genome size. For proteinencoding genes, occulting possible overlaps, there are only alternative start codons and/or truncated stop codons, but the first putative in-frame standard initiation codon or complete stop codon is in the upstream or downstream overlapping ss-*trn* sequences, respectively. Even if, to date, experimental data are missing, stress signals might regulate producing extended or not proteins. Finally, possible implications of tRNA/mRNA hybrid molecules in the "RNA world" to "RNA/protein world" transition will be discussed.

**Keywords:** mitochondrion, tRNA origin, start codon, stop codon, overlap, origin of life, RNA world
