Chapter 7 **Phylogenetic Evolution and Phylogeography of Tibetan Sheep Based on mtDNA D-Loop Sequences 135** Jianbin Liu, Xuezhi Ding, Yufeng Zeng, Xian Guo, Xiaoping Sun and

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

Chao Yuan

Chapter 8 **Mitochondrial Aging and Metabolism: The Importance of a 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, Mónica Ríos-Silva and Blanca Torres-Mendoza

Preface

from transcription.

of an otherwise regular tRNA.

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

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

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

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‐

heavy and light strand replication (and transcription) origins.

Chapter 9 **Long Noncoding Mitochondrial RNAs (LncmtRNAs) as Targets for Cancer Therapy 179** Jaime Villegas Olavarria, Verónica A. Burzio, Vincenzo Borgna, Lorena Lobos-Gonzalez, Mariela Araya, Francisca Guevara, Claudio Villota and Luis O. Burzio

Chapter 10 **Mitochondrial DNA Variations in Tumors: Drivers or Passengers? 195** Edoardo Errichiello and Tiziana Venesio
