Mitochondrial DNA Evolution in Mice

This study extends knowledge of mitochondrial DNA (mtDNA) diversity in mice to include 208 animals belonging to eight species in the subgenus Mus. Highly purified mtDNA from each has been subjected to high-resolution restriction mapping with respect to the known sequence of one mouse mtDNA. Variation attributed to base substitutions was encountered at about 200 of the 300 cleavage sites examined, and a length mutation was located in or near the displacement loop. The variability of different functional regions in this genome was as follows, from least to most: ribosomal RNA, transfer RNA, known proteins, displacement loop and unidentified reading frames.—Phylogenetic analysis confirmed the utility of the Sage and Marshall revision of mouse classification, according to which there are at least four species of commensal mice and three species of aboriginal mice in the complex that was formerly considered to be one species. The most thoroughly studied of these species is Mus domesticus, the house mouse of Western Europe and the Mediterranean region, which is the mitochondrial source of all 50 of the laboratory strains examined and of the representatives of wild house mice introduced by Europeans to North and South America during the past few hundred years.—The level of mtDNA variation among wild representatives of (M. musculus) and several other mammalian species. By contrast, among the many laboratory strains that are known or suspected to stem from the pet mouse trade, there is little interstrain variation, most strains having the "old inbred" type of domesticus mtDNA, whose frequency in the 145 wild mice examined is low, about 0.04. Also notable is the apparent homogeneity of mtDNA in domesticus races that have fixed six or more fused chromosomes and the close relationship of some of these mtDNAs to those of karyotypically normal mice.—In addition, this paper discusses fossil and other evidence for the view that in mice, as in many other mammals, the average rate of point mutational divergence in mtDNA is 2–4% per million years. From this, it is estimated that the commensal association between mice and our ancestors began more than a million years ago, i.e., at an early stage in the evolution of Homo erectus.     

Sequence Evolution of Drosophila Mitochondrial DNA

We have compared nucleotide sequences of corresponding segments of the mitochondrial DNA (mtDNA) molecules of Drosophila yakuba and Drosophila melanogaster, which contain the genes for six proteins and seven tRNAs. The overall frequency of substitution between the nucleotide sequences of these protein genes is 7.2%. As was found for mtDNAs from closely related mammals, most substitutions (86%) in Drosophila mitochondrial protein genes do not result in an amino acid replacement. However, the frequencies of transitions and transversions are approximately equal in Drosophila mtDNAs, which is in contrast to the vast excess of transitions over transversions in mammalian mtDNAs. In Drosophila mtDNAs the frequency of C----T substitutions per codon in the third position is 2.5 times greater among codons of two-codon families than among codons of four-codon families; this is contrary to the hypothesis that third position silent substitutions are neutral in regard to selection. In the third position of codons of four-codon families transversions are 4.6 times more frequent than transitions and A----T substitutions account for 86% of all transversions. Ninety-four percent of all codons in the Drosophila mtDNA segments analyzed end in A or T. However, as this alone cannot account for the observed high frequency of A----T substitutions there must be either a disproportionately high rate of A----T mutation in Drosophila mtDNA or selection bias for the products of A----T mutation. --Consideration of the frequencies of interchange of AGA and AGT codons in the corresponding D. yakuba and D. melanogaster mitochondrial protein genes provides strong support for the view that AGA specifies serine in the Drosophila mitochondrial genetic code.     

Complete Mitochondrial Genomes and Eutherian Evolution

Recent large-scale nuclear DNA phylogenies have supported unconventional interordinal relationships among modern eutherians as well as divergence dates (100 mya) that substantially predate the first appearance of fossils from modern eutherians near the Cretaceous/Cenozoic (K/T) boundary (65-70 mya). For comparison to the nuclear data, I analyzed 12 complete mitochondrial DNA (mtDNA) protein-coding genes (10,677 bp) from 53 eutherian taxa, using maximum-likelihood methods to estimate model parameters (GTR + I + ) and to optimize topology and branch-length estimates. Although closely resembling the nuclear DNA trees, the mtDNA maximum-likelihood tree is just one of seven statistically indistinguishable ( lnL 1.747) trees, each suggesting different evolutionary relationships. This 53-taxon data set and another including 56 taxa provide no statistically significant support for a monophyletic afrotherian clade. In fact, these mitochondrial DNA sequences fail to support the monophyly of three putative eutherian divisions suggested by the nuclear data (Afrotheria, Laurasiatheria or Euarchontoglires). By comparison to well-supported branches describing relationships among families, those describing interordinal relationships are extremely short and only tenuously supported. Neither these sequences, nor sequences simulated under a known tree, fully resolve any interordinal relationship. Even simulated sequences that are twice as long (22kb) as mtDNA protein-coding genes are too short and too saturated to resolve the deepest and shortest interordinal relationships. Further, the mammalian mtDNA sequences appear to depart significantly from molecular-clock and quartet dating assumptions. Unlike recent nuclear DNA studies, I find that mtDNA genes, by themselves, are inadequate to describe relationships or divergence times at the base of the eutherian tree.     

Origin and Evolution of the Mitochondrial Proteome

The endosymbiotic theory for the origin of mitochondria requires substantial modification. The three identifiable ancestral sources to the proteome of mitochondria are proteins descended from the ancestral α-proteobacteria symbiont, proteins with no homology to bacterial orthologs, and diverse proteins with bacterial affinities not derived from α-proteobacteria. Random mutations in the form of deletions large and small seem to have eliminated nonessential genes from the endosymbiont-mitochondrial genome lineages. This process, together with the transfer of genes from the endosymbiont-mitochondrial genome to nuclei, has led to a marked reduction in the size of mitochondrial genomes. All proteins of bacterial descent that are encoded by nuclear genes were probably transferred by the same mechanism, involving the disintegration of mitochondria or bacteria by the intracellular membranous vacuoles of cells to release nucleic acid fragments that transform the nuclear genome. This ongoing process has intermittently introduced bacterial genes to nuclear genomes. The genomes of the last common ancestor of all organisms, in particular of mitochondria, encoded cytochrome oxidase homologues. There are no phylogenetic indications either in the mitochondrial proteome or in the nuclear genomes that the initial or subsequent function of the ancestor to the mitochondria was anaerobic. In contrast, there are indications that relatively advanced eukaryotes adapted to anaerobiosis by dismantling their mitochondria and refitting them as hydrogenosomes. Accordingly, a continuous history of aerobic respiration seems to have been the fate of most mitochondrial lineages. The initial phases of this history may have involved aerobic respiration by the symbiont functioning as a scavenger of toxic oxygen. The transition to mitochondria capable of active ATP export to the host cell seems to have required recruitment of eukaryotic ATP transport proteins from the nucleus. The identity of the ancestral host of the α-proteobacterial endosymbiont is unclear, but there is no indication that it was an autotroph. There are no indications of a specific α-proteobacterial origin to genes for glycolysis. In the absence of data to the contrary, it is assumed that the ancestral host cell was a heterotroph.     

The Mitochondrial Genome of Raphanus sativus and Gene Evolution of Cruciferous Mitochondrial Types

To explore the mitochondrial genes of the Cruciferae family, the mitochondrial genome of Raphanus sativus (sat) was sequenced and annotated. The circular mitochondrial genome of sat is 239,723 bp and includes 33 protein-coding genes, three rRNA genes and 17 tRNA genes. The mitochondrial genome also contains a pair of large repeat sequences 5.9 kb in length, which may mediate genome reorga-nization into two sub-genomic circles, with predicted sizes of 124.8 kb and 115.0 kb, respectively. Furthermore, gene evolution of mitochondrial genomes within the Cruciferae family was analyzed using sat mitochondrial type (mitotype), together with six other re-ported mitotypes. The cruciferous mitochondrial genomes have maintained almost the same set of functional genes. Compared with Cycas taitungensis (a representative gymnosperm), the mitochondrial genomes of the Cruciferae have lost nine protein-coding genes and seven mitochondrial-like tRNA genes, but acquired six chloroplast-like tRNAs. Among the Cruciferae, to maintain the same set of genes that are necessary for mitochondrial function, the exons of the genes have changed at the lowest rates, as indicated by the numbers of single nucleotide polymorphisms. The open reading frames (ORFs) of unknown function in the cruciferous genomes are not conserved. Evolutionary events, such as mutations, genome reorganizations and sequence insertions or deletions (indels), have resulted in the non- conserved ORFs in the cruciferous mitochondrial genomes, which is becoming significantly different among mitotypes. This work represents the first phylogenic explanation of the evolution of genes of known function in the Cruciferae family. It revealed significant variation in ORFs and the causes of such variation.     

Plant Mitochondrial Genome Evolution and Cytoplasmic Male Sterility

Mitochondria are responsible for providing energy currency to life processes in the molecular form of ATP and are therefore typically referred to as the power factories of cells. Plant mitochondria are also relevant to the common phenomenon of cytoplasmic male sterility, which is agronomically important in various crop species. Cytoplasmic male sterility (CMS) is a complex trait that may be influenced by patterns of mitochondrial genome evolution, and by intergenomic gene transfer among the organellar and nuclear compartments of plant cells. Here, we review patterns and processes that shape plant mitochondrial genomes, some relevant interactions between organelles, and the general features shared by the majority of cytoplasmic male-sterile genes in plants to further the goal of understanding CMS.     

线粒体的分子进化与氧效应

线粒体通常被认为是消耗氧气产生ATP的细胞器.但自然界有多种生物具有厌氧型线粒体,其厌氧生物化学和遗传学研究表明,线粒体可能来源于兼性厌氧的α-蛋白细菌,在有氧环境中,起始共生体的厌氧功能丧失或被改变而进化成为经典的线粒体,但在厌氧环境中,有氧呼吸功能丧失了进化.厌氧型线粒体为了完成能量的转化,改变了呼吸链的组成,表现出产能模式的多样性.而经典线粒体在利用氧化反应获得能量的同时,也通过电子漏产生了自由基,对生命体本身构成了威胁.事实上,生命体呼吸链的进化是沿着不断加强对氧的利用效率和不断克服氧毒性的方向发展的.     

Neutral and Non-Neutral Evolution of Drosophila Mitochondrial DNA

To test hypotheses of neutral evolution of mitochondrial DNA (mtDNA), nucleotide sequences were determined for 1515 base pairs of the NADH dehydrogenase subunit 5 (ND5) gene in the mitochondrial DNA of 29 lines of Drosophila melanogaster and 9 lines of its sibling species Drosophila simulans. In contrast to the patterns for nuclear genes, where D. melanogaster generally exhibits much less nucleotide polymorphism, the number of segregating sites was slightly higher in a global sample of nine ND5 sequences in D. melanogaster (s = 8) than in the nine lines of D. simulans (s = 6). When compared to variation at nuclear loci, the mtDNA variation in D. melanogaster does not depart from neutral expectations. The ND5 sequences in D. simulans, however, show fewer than half the number of variable sites expected under neutrality when compared to sequences from the period locus. While this reduction in variation is not significant at the 5% level, HKA tests with published restriction data for mtDNA in D. simulans do show a significant reduction of variation suggesting a selective sweep of variation in the mtDNA in this species. Tests of neutral evolution based on the ratios of synonymous and replacement polymorphism and divergence are generally consistent with neutral expectations, although a significant excess of amino acid polymorphism within both species is localized in one region of the protein. The rate of mtDNA evolution has been faster in D. melanogaster than in D. simulans and the population structure of mtDNA is distinct in these species. The data reveal how different rates of mtDNA evolution between species and different histories of neutral and adaptive evolution within species can compromise historical inferences in population and evolutionary biology.     

The Evolution of tRNA-Leu Genes in Animal Mitochondrial Genomes

Abstract We report the results of a comparative analysis of the sequences of multicomponent monooxygenases, a family of enzymes of great interest for bioremediation of contaminated soil. We show that their function, in terms of substrate specificity, can be deduced from their subunit organization and composition, that rearrangements of subunits as well as recruitments of new ones can be used to explain their different properties and functionalities, and that the observed pattern can be rationalized invoking a number of evolutionary events, including horizontal gene transfer. Our analysis highlights the plasticity and modularity of this family of enzymes, which might very well be the reason underlying the extremely rapid emergence of new bacterial strains able to grow on contaminated soils.     

Lineage-Specific Evolution of Echinoderm Mitochondrial ATP Synthase Subunit 8

Peculiar evolutionary properties of the subunit 8 of mitochondrial ATP synthase (ATPase8) are revealed by comparative analyses carried out between both closely and distantly related species of echinoderms. The analysis of nucleotide substitution in the three echinoids demonstrated a relaxation of amino acid functional constraints. The deduced protein sequences display a well conserved domain at the N-terminus, while the central part is very variable. At the C-terminus, the broad distribution of positively charged amino acids, which is typical of other organisms, is not conserved in the two different echinoderm classes of the sea urchins and of the sea stars. Instead, a motif of three amino acids, so far not described elsewhere, is conserved in sea urchins and is found to be very similar to the motif present in the sea stars. Our results indicate that the N-terminal region seems to follow the same evolutionary pattern in different organisms, while the maintenance of the C-terminal part in a phylum-specific manner may reflect the co-evolution of mitochondrial and nuclear genes.     

Mitochondrial DNA Evidence and Evolution in Varanoidea (Squamata)

Varanoidea is a monophyletic group of anguimorph lizards, comprising the New World helodermatids, the Bornean earless monitor Lanthanotus borneensis , and the Old World monitors ( Varanus ). I use mitochondrial DNA sequences and extensive taxonomic sampling to test alternative hypotheses of varanoid relationships. The most parsimonious hypothesis confirms the monophyly of Varanoidea ( Heloderma, Lanthanotus , and Varanus ) and Varanus , as well as the sister-taxon relationship of Varanus and Lanthanotus . The relationships among Varanus species differ in several respects from previous hypotheses. Three major lineages are recognized within Varanus : an African clade basal to the rest of the group, an Indo-Asian clade, and an Indo-Australian clade. Within the last lineage, the endemic Australian dwarf monitors ( Odatria ) form a clade sister to the large Australian monitors (the gouldii group). Tests of the effects of rate heterogeneity and homoplasy demonstrate that putative process partitions of data are largely congruent with one another and contribute positive support to the overall hypothesis.     

Evolution of the Mitochondrial Cytochrome Oxidase II Gene in Collembola

The sequence of the mitochondrial COII gene has been widely used to estimate phylogenetic relationships at different taxomonic levels across insects. We investigated the molecular evolution of the COII gene and its usefulness for reconstructing phylogenetic relationships within and among four collembolan families. The collembolan COII gene showed the lowest A + T content of all insects so far examined, confirming that the well-known A + T bias in insect mitochondrial genes tends to increase from the basal to apical orders. Fifty-seven percent of all nucleotide positions were variable and most of the third codon positions appeared free to vary. Values of genetic distance between congeneric species and between families were remarkably high; in some cases the latter were higher than divergence values between other orders of insects. The remarkably high divergence levels observed here provide evidence that collembolan taxa are quite old; divergence levels among collembolan families equaled or exceeded divergences among pterygote insect orders. Once the saturated third-codon positions (which violated stationarity of base frequencies) were removed, the COII sequences contained phylogenetic information, but the extent of that information was overestimated by parsimony methods relative to likelihood methods. In the phylogenetic analysis, consistent statistical support was obtained for the monophyly of all four genera examined, but relationships among genera/families were not well supported. Within the genus Orchesella, relationships were well resolved and agreed with allozyme data. Within the genus Isotomurus, although three pairs of populations were consistently identified, these appeared to have arisen in a burst of evolution from an earlier ancestor. Isotomurus italicus always appeared as basal and I. palustris appeared to harbor a cryptic species, corroborating allozyme data. Received: 12 January 1996 / Accepted: 10 August 1996     

金丝猴属的DNA序列变异及进化与保护遗传学研究

金丝猴的分类及系统发育存在许多争议。本文测定了２只川金丝猴、８只滇金丝猴、１只越南金丝猴和１只灰叶猴的２５３ｂｐ的线粒体细胞色素ｂ基因的序列。其中４７个位点（１９％）检出变异。我们采用简约法、最大似然法和距离法构建了一系列的分子系统树,得到相同的拓扑结构,从而可能在分子水平澄清了金丝猴属的系统发育。结果表明,云南金丝猴与越南金丝猴间的关系较与川金丝猴的为近。金丝猴属的分化大约发生在２～６百万年以前。这３种金丝猴均是独立的种,且都应归入金丝猴属。对８只来自野外的滇金丝猴（其中包括了昆明动物研究所圈养群体的所有６只创立者）的非损伤性遗传分析提示,编号为ＹＫ２的母猴是维持该圈养群体遗传多样性的关键猴。我们建立的这种非损伤性遗传分析方法广泛适用于珍稀濒危动物的遗传多样性及遗传管理研究。     

Experimental Relocation of the Mitochondrial ATP9 Gene to the Nucleus Reveals Forces Underlying Mitochondrial Genome Evolution

Only a few genes remain in the mitochondrial genome retained by every eukaryotic organism that carry out essential functions and are implicated in severe diseases. Experimentally relocating these few genes to the nucleus therefore has both therapeutic and evolutionary implications. Numerous unproductive attempts have been made to do so, with a total of only 5 successes across all organisms. We have taken a novel approach to relocating mitochondrial genes that utilizes naturally nuclear versions from other organisms. We demonstrate this approach on subunit 9/c of ATP synthase, successfully relocating this gene for the first time in any organism by expressing the ATP9 genes from Podospora anserina in Saccharomyces cerevisiae. This study substantiates the role of protein structure in mitochondrial gene transfer: expression of chimeric constructs reveals that the P. anserina proteins can be correctly imported into mitochondria due to reduced hydrophobicity of the first transmembrane segment. Nuclear expression of ATP9, while permitting almost fully functional oxidative phosphorylation, perturbs many cellular properties, including cellular morphology, and activates the heat shock response. Altogether, our study establishes a novel strategy for allotopic expression of mitochondrial genes, demonstrates the complex adaptations required to relocate ATP9, and indicates a reason that this gene was only transferred to the nucleus during the evolution of multicellular organisms.     

Covariation of Mitochondrial Genome Size with Gene Lengths: Evidence for Gene Length Reduction During Mitochondrial Evolution

Reduction of genome size and gene shortening have been observed in a number of parasitic and mutualistic intracellular symbionts. Reduction of coding capacity is also a unifying principle in the evolutionary history of mitochondria, but little is known about the evolution of gene length in mitochondria. The genes for cytochrome c oxidase subunits I–III, cytochrome b, and the large and small subunit rRNAs are, with very few exceptions, always found on the mitochondrial genome. These resident mitochondrial genes can therefore be used to test whether the reduction in gene lengths observed in a number of intracellular symbionts is also seen in mitochondria. Here we show that resident mitochondrial gene products are shorter than their corresponding counterparts in -proteobacteria and, furthermore, that the reduction of mitochondrial genome size is correlated with a reduction in the length of the corresponding resident gene products. We show that relative genomic AT content, which has been identified as a factor influencing gene lengths in other systems, cannot explain gene length/genome size covariance observed in mitochondria. Our data are therefore in agreement with the idea that gene length evolves as a consequence of selection for smaller genomes, either to avoid accumulation of deleterious mutations or triggered by selection for a replication advantage.     

Mitochondrial DNA Genetics and the Heteroplasmy Conundrum in Evolution and Disease

The unorthodox genetics of the mtDNA is providing new perspectives on the etiology of the common “complex” diseases. The maternally inherited mtDNA codes for essential energy genes, is present in thousands of copies per cell, and has a very high mutation rate. New mtDNA mutations arise among thousands of other mtDNAs. The mechanisms by which these “heteroplasmic” mtDNA mutations come to predominate in the female germline and somatic tissues is poorly understood, but essential for understanding the clinical variability of a range of diseases. Maternal inheritance and heteroplasmy also pose major challengers for the diagnosis and prevention of mtDNA disease.     

The Rates of Molecular Evolution in Rodent and Primate Mitochondrial DNA

A higher rate of molecular evolution in rodents than in primates at synonymous sites and, to a lesser extent, at amino acid replacement sites has been reported previously for most nuclear genes examined. Thus in these genes the average ratio of amino acid replacement to synonymous substitution rates in rodents is lower than in primates, an observation at odds with the neutral model of molecular evolution. Under Ohta's mildly deleterious model of molecular evolution, these observations are seen as the consequence of the combined effects of a shorter generation time (driving a higher mutation rate) and a larger effective population size (resulting in more effective selection against mildly deleterious mutations) in rodents. The present study reports the results of a maximum-likelihood analysis of the ratio of amino acid replacements to synonymous substitutions for genes encoded in mitochondrial DNA (mtDNA) in these two lineages. A similar pattern is observed: in rodents this ratio is significantly lower than in primates, again consistent only with the mildly deleterious model. Interestingly the lineage-specific difference is much more pronounced in mtDNA-encoded than in nuclear-encoded proteins, an observation which is shown to run counter to expectation under Ohta's model. Finally, accepting certain fossil divergence dates, the lineage-specific difference in amino acid replacement-to-synonymous substitution ratio in mtDNA can be partitioned and is found to be entirely the consequence of a higher mutation rate in rodents. This conclusion is consistent with a replication-dependent model of mutation in mtDNA. Received: 24 September 1999 / Accepted: 18 September 2000