The complete sequence of the 16,569-base pair human mitochondrial genome is presented. The genes for the 12S and 16S rRNAs, 22 tRNAs, cytochrome c oxidase subunits I, II and III, ATPase subunit 6, cytochrome b and eight other predicted protein coding genes have been located. The sequence shows extreme economy in that the genes have none or only a few noncoding bases between them, and in many cases the termination codons are not coded in the DNA but are created post-transcriptionally by polyadenylation of the mRNAs.

Sequence and organization of the human mitochondrial genome

The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme

A 3'-end proximal segment of most of the putative mRNAs encoded in the heavy strand of HeLa cell mtDNA has been partially sequences and aligned with the DNA sequence. In all cases, the 3'-end nucleotide of the individual mRNA coding sequences has been found to be immediately contiguous to a tRNA gene or another mRNA coding sequence. These and previous results indicate that the heavy (H) strand sequences coding for the rRNA, poly(A)-containing RNA and tRNA species form a continuum extending over almost the entire length of this strand. We propose that the H strand is transcribed into a single polycistronic RNA molecule, which is processed later into mature species by precise endonucleolytic cleavages which occur, in most cases, immediately before and after a tRNA sequence.

tRNA punctuation model of RNA processing in human mitochondria

Sequence and gene organization of mouse mitochondrial DNA

In the past decade, mitochondrial DNA (mtDNA) analysis has become established as a powerful tool for evolutionary studies of animals. These studies, recently reviewed by Avise (8) and Wilson et al (149), have used mtDNA analyses to provide insights into population structure and gene flow, hybridization, biogeography, and phylogenetic relationships. Major advances have been made in our understanding of the molecular biology of animal mtDNA (reviewed in 7, 28). A powerful synergism exists between the two fields of research: Evolutionary studies provide comparative data on mtDNA organization and function, and molecular investigations can, and should, improve the level of sophistication of evolutionary studies that use mtDNA. Here we focus on molecular aspects of animal mtDNA that are especially relevant to its use in evolutionary studies. Thus, we consider the form and frequency of three types of change in mtDNA: base substitution, length variation, and sequence rearrangement. Attention is also given to the nature and possible consequences of interactions between nuclear and mitochondrial (mt) genes. In the concluding sections, we discuss the way in which the knowledge of molecular processes allows informed use of mtDNA variation in evolutionary studies. Only animal mtDNAs are considered. The molecular biology and evolution of chloroplast DNA and nonmetazoan mtDNAs have been reviewed elsewhere (41, 66, 111, 121, 123).

https://www.jstor.org/stable/pdfplus/2097133.pdf

Evolution of animal mitochondrial dna: relevance for population biology and systematics

The tRNA genes punctuate the reading of genetic information in human mitochondrial DNA

Fractionation of mitochondrial RNA from HeLa cells by high-resolution electrophoresis under strongly denaturing conditions☆

In the past 2 years, the determination of the complete sequence of the human and bovine mtDNAs by Sanger’s group in Cambridge, England (see Anderson et al., this volume) has revealed the unique features of the genetic code and of the gene organization in the mammalian mitochondrial genome (Anderson et al. 1981). The parallel work carried out in our laboratory on the organization of the mtDNA transcripts in HeLa cells has produced a perfectly matching picture, providing at the same time important information on both the structure of the mitochondrial genes and their mode of expression (Ojala et al. 1980Ojala et al. 1981; Montoya et al. 1981). Thus, the extraordinarily compact gene organization of the mammalian mtDNA, with its continuous genes mostly butt-jointed to each other and a nearly complete absence of noncoding stretches, has been shown to have its precise counterpart in the tight arrangement of the mtDNA transcripts and in the distinctive structural features of the mitochondrial mRNAs. Moreover, the interspersion of the tRNA genes with the rRNA and protein-coding genes and their immediate juxtaposition have pointed to an additional functional role for tRNA sequences related to their positions in mtDNA, namely, as recognition signals for RNA processing (Attardi et al. 1980a; Ojala et al. 1981). The information on the structural organization of the genes and their transcripts in the human mitochondrial genome has further provided the framework for an in-depth analysis of the metabolic behavior of mtRNAs in HeLa cells (Gelfand and Attardi 1981). The correlation and integration of...

A Comprehensive View of Mitochondrial Gene Expression in Human Cells

The organization of the genes in the human mitochondrial genome and their mode of transcription are being investigated by a detailed mapping, structural and metabolic analysis of the various discrete poly(A)-containing and non-poly(A)-containing RNA species coded for by mitochondrial DNA (mit-DNA). Several approaches, involving different RNA-DNA hybridization techniques, RNA and DNA sequencing methods, and analysis of kinetic behavior, are being used in this work. A fine structural study of the ribosomal RNA region of mit-DNA has failed to reveal the presence of inserts in the main body of the 12S and 16S rRNA cistrons. The sequence of 71 nucleotides at the 5′-end of 12S rRNA and that of 32 nucleotides at the 5′-end of 16S rRNA have been determined. Experiments of hybridization of nascent RNA chains with different restriction fragments of mitochondrial DNA have led to the identification in this DNA of a region containing a point of initiation of L strand transcription. Several giant poly(A)-containing and non-poly(A)-containing L strand transcripts have been identified and characterized in their map location and metabolic behavior.

Christian Merkel

Papers

The tRNA genes punctuate the reading of genetic information in human mitochondrial DNA

Fractionation of mitochondrial RNA from HeLa cells by high-resolution electrophoresis under strongly denaturing conditions☆

A Comprehensive View of Mitochondrial Gene Expression in Human Cells

The organization of the genes in the human mitochondrial genome and their mode of transcription