Mitochondrial genome in animal cells

In the past decade, the development of new DNA, RNA, and protein technologies has greatly incremented the knowledge about the organization and expression of mitochondrial DNA. The complete base sequence of mitochondrial DNA of several animals is known and many data are rapidly accumulating on the mitochondrial genomes of other systems. Here we discuss the results so far obtained that disclosed unexpected features of mitochondrial genetics. Furthermore, mitochondrial DNA has become established as a powerful tool for evolutionary studies in animals. Evidences are preented demonstrating that the evolution of mitochondrial DNA has proceeded in different ways in the various taxonomic groups. Data on heteroplasmic animals, which demonstrate the rapid evolution of mitochondrial DNA, are also presented.     

Influence of hydrogeographic history and hybridization on the distribution of genetic variation in the pupfishes Cyprinodon atrorus and C. bifasciatus

The evolutionary importance of hybridization in animals has been subject of much debate. In this study, we examined the influence of hydrogeographic history and hybridization on the present distribution of nuclear and mitochondrial DNA variation in two pupfish species, Cyprinodon atrorus and Cyprinodon bifasciatus. Results presented here indicate that there has been limited introgression of nuclear genes; however, mtDNA introgression has been substantial, with complete replacement of the C. bifasciatus mitochondrial genome by that of C. atrorus. Subsequent to this replacement, there has been diversification of mitochondrial haplotypes along major geographic regions in the basin. Evidence was also found that mitochondrial replacement follows a predictable, cyclical pattern in this system, with isolation and diversification followed by re-contact and replacement of C. bifasciatus mitochondrial haplotypes by those of C. atrorus. This pattern is best explained by a combination of a numeric bias towards C. atrorus and mating site selection rather than selection for C. atrorus mitochondrial genome. These results demonstrate the important role hybridization can play in evolution.     

The Mitochondrial Genome of Protists

The data on the structure and functions of the mitochondrial genomes of protists (Protozoa and unicellular red and green algae) are reviewed. It is emphasized that mitochondrial gene structure and composition, as well as organization of mitochondrial genomes in protists are more diverse than in multicellular eukaryotes. The gene content of mitochondrial genomes of protists are closer to those of plants than animals or fungi. In the protist mitochondrial DNA, both the universal (as in higher plants) and modified (as in animals and fungi) genetic codes are used. In the overwhelming majority of cases, protist mitochondrial genomes code for the major and minor rRNA components, some tRNAs, and about 30 proteins of the respiratory chain and ribosomes. Based on comparison of the mitochondrial genomes of various protists, the origin and evolution of mitochondria are briefly discussed.     

The mitochondrial genome of protists

The data on the structure and functions of the mitochondrial genomes of protists (Protozoa and unicellular red and green algae) are reviewed. It is emphasized that mitochondrial gene structure and composition, as well as organization of mitochondrial genomes in protists are more diverse than in multicellular eukaryotes. The gene content of mitochondrial genomes of protists are closer to those of plants than animals or fungi. In the protist mitochondrial DNA, both the universal (as in higher plants) and modified (as in animals and fungi) genetic codes are used. In the overwhelming majority of cases, protist mitochondrial genomes code for the major and minor rRNA components, some tRNAs, and about 30 proteins of the respiratory chain and ribosomes. Based on comparison of the mitochondrial genomes of various protists, the origin and evolution of mitochondria are briefly discussed.     

Episodes of adaptive evolution of mitochondrial genome in asiatic salamanders (Amphibia,Caudata, Hynobiidae)

To elucidate the effect of natural selection on the evolution of mitochondrial DNA (mtDNA) in Asiatic salamanders of the family Hynobiidae, nucleotide sequences of 12 protein-coding genes were analyzed. Using a mixed effects model of evolution, it was found that, in spite of the pronounced effect of negative selection on the mtDNA evolution in Hynobiidae (which is typical for the animals in general), two phylogenetic clusters, the West Asian one, represented by the genera Ranodon and Paradactylodon, and North Eurasian one, represented by the genus Salamandrella, were formed under the influence of episodic positive selection. Analysis of protein sequences encoded by the mitochondrial genome also supported the influence of positive selection on the evolution of Hynobiidae at some stages of their cladogenesis. It is suggested that the signatures of adaptive evolution detected in the mtDNA of Hynobiidae were determined by the complex and long-lasting history of their formation, accompanied by adaptation to the changing environment.     

Inheritance and recombination of mitochondrial genomes in plants, fungi and animals

It is generally assumed that mitochondrial genomes are uniparentally transmitted, homoplasmic and nonrecombining. However, these assumptions draw largely from early studies on animal mitochondrial DNA (mtDNA). In this review, we show that plants, animals and fungi are all characterized by episodes of biparental inheritance, recombination among genetically distinct partners, and selfish elements within the mitochondrial genome, but that the extent of these phenomena may vary substantially across taxa. We argue that occasional biparental mitochondrial transmission may allow organisms to achieve the best of both worlds by facilitating mutational clearance but continuing to restrict the spread of selfish genetic elements. We also show that methodological biases and disproportionately allocated study effort are likely to have influenced current estimates of the extent of biparental inheritance, heteroplasmy and recombination in mitochondrial genomes from different taxa. Despite these complications, there do seem to be discernible similarities and differences in transmission dynamics and likelihood of recombination of mtDNA in plant, animal and fungal taxa that should provide an excellent opportunity for comparative investigation of the evolution of mitochondrial genome dynamics.     

Positive and negative selection on the mitochondrial genome

Several recent studies have confirmed that mitochondrial DNA variation and evolution are not consistent with the neutral theory of molecular evolution and might be inappropriate for estimating effective population sizes. Evidence for the action of both positive and negative selection on mitochondrial genes has been put forward, and the complex genetics of mitochondrial DNA adds to the challenge of resolving this debate. The solution could lie in distinguishing genetic drift from 'genetic draft' and in dissecting the physiology of mitochondrial fitness.     

Research on mitochondria and aging, 2006-2007

This review focuses on some of the 'hot topics' that fall under the general heading 'mitochondria and aging'. For each selected topic, we highlight recent publications that have either addressed specific problems within the field or presented novel findings of interest regarding the links between mitochondria and aging. These include studies on the structure of complex I and the mechanisms of superoxide production by this complex; work showing a novel site of hydrogen peroxide production within mitochondria that is modulated by caloric restriction; explorations of the relationship between the rate of evolution of mitochondrial DNA and lifespan; a demonstration that mitochondrial DNA mutations do not limit lifespan in mice; and investigations of the effects of mitochondrial fission on aging. We also list other relevant articles of interest and suggest some key challenges for the field in the near future.     

Genetic hitchhiking,mitonuclear coadaptation,and the origins of mt DNA barcode gaps

DNA barcoding based on mitochondrial (mt) nucleotide sequences is an enigma. Neutral models of mt evolution predict DNA barcoding cannot work for recently diverged taxa, and yet, mt DNA barcoding accurately delimits species for many bilaterian animals. Meanwhile, mt DNA barcoding often fails for plants and fungi. I propose that because mt gene products must cofunction with nuclear gene products, the evolution of mt genomes is best understood with full consideration of the two environments that impose selective pressure on mt genes: the external environment and the internal genomic environment. Moreover, it is critical to fully consider the potential for adaptive evolution of not just protein products of mt genes but also of mt transfer RNAs and mt ribosomal RNAs. The tight linkage of genes on mt genomes that do not engage in recombination could facilitate selective sweeps whenever there is positive selection on any element in the mt genome, leading to the purging of mt genetic diversity within a population and to the rapid fixation of novel mt DNA sequences. Accordingly, the most important factor determining whether or not mt DNA sequences diagnose species boundaries may be the extent to which the mt chromosomes engage in recombination.     

Nucleotide sequence and evolution of the 18S ribosomal RNA gene in maize mitochondria.

The nucleotide sequence of the gene coding for the 18S ribosomal RNA of maize mitochondria has been determined and a model for the secondary structure is proposed. Dot matrix analysis has been used to compare the extent and distribution of sequence similarities of the entire maize mitochondrial 18S rRNA sequence with that of 15 other small subunit rRNA sequences. The mitochondrial gene shows great similarity to the eubacterial sequences and to the maize chloroplast, and less similarity to mitochondrial rRNA genes in animals and fungi. We propose that this similarity is due to a slow rate of nucleotide divergence in plant mtDNA compared to the mtDNA of animals. Sequence comparisons indicate that the evolution of the maize mitochondrial 18S, chloroplast 16S and nuclear 17S ribosomal genes have been essentially independent, in spite of evidence for DNA transfer between organelles and the nucleus.     

Similar relative mutation rates in the three genetic compartments of Mesostigma and Chlamydomonas

Levels of nucleotide substitution at silent sites in organelle versus nuclear DNAs have been used to estimate relative mutation rates among these compartments and explain lineage-specific features of genome evolution. Synonymous substitution divergence values in animals suggest that the rate of mutation in the mitochondrial DNA is 10-50 times higher than that of the nuclear DNA, whereas overall data for most seed plants support relative mutation rates in mitochondrial, plastid, and nuclear DNAs of 1:3:10. Little is known about relative mutation rates in green algae, as substitution rate data is limited to only the mitochondrial and nuclear genomes of the chlorophyte Chlamydomonas. Here, we measure silent-site substitution rates in the plastid DNA of Chlamydomonas and the three genetic compartments of the streptophyte green alga Mesostigma. In contrast to the situation in animals and land plants, our results support similar relative mutation rates among the three genetic compartments of both Chlamydomonas and Mesostigma. These data are discussed in relation to published intra-species genetic diversity data for the three genetic compartments of Chlamydomonas and are ultimately used to address contemporary hypotheses on the organelle genome evolution. To guide future work, we describe evolutionary divergence data of all publically available Mesostigma viride strains and identify, for the first time, three distinct lineages of Mesostigma.     

Thermal habit, metabolic rate and the evolution of mitochondrial DNA

The hallmarks of animal mitochondrial DNA (mtDNA) are a rapid rate of sequence evolution, a small genome carrying the same set of homologous genes, maternal inheritance and lack of recombination. Over the past few years, a variety of different observations has challenged these accepted notions of mitochondrial biology. Notable examples include evidence for variable rates of mtDNA sequence evolution among taxa, evidence for large and variable mitochondrial genome sizes in certain groups, and a growing number of cases in metazoans of 'paternal leakage' in the inheritance of mtDNA. Several recent studies have uncovered different lines of evidence suggesting that an organism's thermal habit, or metabolic rate, can influence the evolution of mtDNA.     

Divergence of mitochondrial dna is not corroborated by nuclear dna, morphology, or behavior in Drosophila simulans

We ask whether the observed mitochondrial DNA (mtDNA) population subdivision of Drosophila simulans is indicative of organismal structure or of specific processes acting on the mitochondrial genome. Factors either intrinsic or extrinsic to the host genome may influence the evolutionary dynamics of mtDNA. Potential intrinsic factors include adaptation of the mitochondrial genome and of nucleomitochondrial gene complexes specific to the local environment. An extrinsic force that has been shown to influence mtDNA evolution in invertebrates is the bacterial endosymbiont Wolbachia. Evidence presented in this study suggests that mtDNA is not a good indicator of organismal subdivision in D. simulans. Furthermore, there is no evidence to suggest that Wolbachia causes any reduction in nuclear gene flow in this species. The observed differentiation in mtDNA is not corroborated by data from NADH: ubiquinone reductase 75kD subunit precursor or the Alcohol dehydrogenase-related loci, from the shape or size of the male genital arch, or from assortative premating behavior. We discuss these results in relation to a mitochondrial genetic species concept and the potential for Wolbachia-induced incompatibility to be a mechanism of speciation in insects. We conclude with an iterated appeal to include phylogenetic and statistical tests of neutrality as a supplement to phylogenetic and population genetic analyses when using mtDNA as an evolutionary marker.     

Oxidative stress, mitochondrial DNA mutation, and apoptosis in aging

A wide spectrum of alterations in mitochondria and mitochondrial DNA (mtDNA) with aging has been observed in animals and humans. These include (i) decline in mitochondrial respiratory function; (ii) increase in mitochondrial production of reactive oxygen species (ROS) and the extent of oxidative damage to DNA, proteins, and lipids; (iii) accumulation of point mutations and large-scale deletions of mtDNA; and (iv) enhanced apoptosis. Recent studies have provided abundant evidence to substantiate the importance of mitochondrial production of ROS in aging. On the other hand, somatic mtDNA mutations can cause premature aging without increasing ROS production. In this review, we focus on the roles that ROS play in the aging-associated decline of mitochondrial respiratory function, accumulation of mtDNA mutations, apoptosis, and alteration of gene expression profiles. Taking these findings together, we suggest that mitochondrial dysfunction, enhanced oxidative stress, subsequent accumulation of mtDNA mutations, altered expression of a few clusters of genes, and apoptosis are important contributors to human aging.     

Do mitochondria recombine in humans?

Until very recently, mitochondria were thought to be clonally inherited through the maternal line in most higher animals. However, three papers published in 2000 claimed population-genetic evidence of recombination in human mitochondrial DNA. Here I review the current state of the debate. I review the evidence for the two main pathways by which recombination might occur: through paternal leakage and via a mitochondrial DNA sequence in the nuclear genome. There is no strong evidence for either pathway, although paternal leakage seems a definite possibility. However, the population-genetic evidence, although not conclusive, is strongly suggestive of recombination in mitochondrial DNA. The implications of non-clonality for our understanding of human and mitochondrial evolution are discussed.     

Energy,ageing, fidelity and sex: oocyte mitochondrial DNA as a protected genetic template

Oxidative phosphorylation couples ATP synthesis to respiratory electron transport. In eukaryotes, this coupling occurs in mitochondria, which carry DNA. Respiratory electron transport in the presence of molecular oxygen generates free radicals, reactive oxygen species (ROS), which are mutagenic. In animals, mutational damage to mitochondrial DNA therefore accumulates within the lifespan of the individual. Fertilization generally requires motility of one gamete, and motility requires ATP. It has been proposed that oxidative phosphorylation is nevertheless absent in the special case of quiescent, template mitochondria, that these remain sequestered in oocytes and female germ lines and that oocyte mitochondrial DNA is thus protected from damage, but evidence to support that view has hitherto been lacking. Here we show that female gametes of Aurelia aurita, the common jellyfish, do not transcribe mitochondrial DNA, lack electron transport, and produce no free radicals. In contrast, male gametes actively transcribe mitochondrial genes for respiratory chain components and produce ROS. Electron microscopy shows that this functional division of labour between sperm and egg is accompanied by contrasting mitochondrial morphology. We suggest that mitochondrial anisogamy underlies division of any animal species into two sexes with complementary roles in sexual reproduction. We predict that quiescent oocyte mitochondria contain DNA as an unexpressed template that avoids mutational accumulation by being transmitted through the female germ line. The active descendants of oocyte mitochondria perform oxidative phosphorylation in somatic cells and in male gametes of each new generation, and the mutations that they accumulated are not inherited. We propose that the avoidance of ROS-dependent mutation is the evolutionary pressure underlying maternal mitochondrial inheritance and the developmental origin of the female germ line.     

Slow mitochondrial DNA sequence evolution in the Anthozoa (Cnidaria)

Mitochondrial genes have been used extensively in population genetic and phylogeographical analyses, in part due to a high rate of nucleotide substitution in animal mitochondrial DNA (mtDNA). Nucleotide sequences of anthozoan mitochondrial genes, however, are virtually invariant among conspecifics, even at third codon positions of protein-coding sequences. Hence, mtDNA markers are of limited use for population-level studies in these organisms. Mitochondrial gene sequence divergence among anthozoan species is also low relative to that exhibited in other animals, although higher level relationships can be resolved with these markers. Substitution rates in anthozoan nuclear genes are much higher than in mitochondrial genes, whereas nuclear genes in other metazoans usually evolve more slowly than, or similar to, mitochondrial genes. Although several mechanisms accounting for a slow rate of sequence evolution have been proposed, there is not yet a definitive explanation for this observation. Slow evolution and unique characteristics may be common in primitive metazoans, suggesting that patterns of mtDNA evolution in these organisms differ from that in other animal systems.     

Analysis of the complete human mtDNA genome: methodology and inferences for human evolution

The analysis of mitochondrial DNA (mtDNA) sequences has been a potent tool in our understanding of human evolution. However, almost all studies of human evolution based on mtDNA sequencing have focused on the control region, which constitutes less than 7% of the mitochondrial genome. The rapid development of technology for automated DNA sequencing has made it possible to study the complete mtDNA genomes in large numbers of individuals, opening the field of mitochondrial population genomics. Here we describe a suitable methodology for determining the complete human mitochondrial sequence and the global mtDNA diversity in humans. Also, we discuss the implications of the results with respect to the different hypotheses for the evolution of modern humans.