The Mitochondrial Genome and Human Mitochondrial Diseases

To date, more than 100 point mutations and several hundreds of structural rearrangements of mitochondrial DNA (mtDNA) are known too be connected with characteristic neuromuscular and other mitochondrial syndromes varying form those causing death at the neonatal stage to diseases with late ages of onset. The immediate cause of mitochondrial disorders is a defective oxidative phosphorylation. Wide phenotypic variation and the heteroplasmy phenomenon, which some authors include in mutation load, are characteristic of human mitochondrial diseases. As the numbers of cases identified and pedigrees described increase, data on the genotype–phenotype interaction and the structure and frequency of pathogenic and conditionally pathogenic mtDNA mutations in human populations are rapidly accumulated. The data on the genetics and epidemiology of mitochondrial diseases are not only important for differential diagnosis and genetic counseling. Since both neutral and mildly pathogenic mutations of mtDNA are progressively accumulated in maternal phyletic lines, molecular analysis of these mutations permits not only reconstruction of the genealogical tree of modern humans, but also estimation of the role that these mutations play in natural selection.     

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.     

后生动物线粒体基因组:起源、大小和基因排列进化

由于受到强烈的进化约束,后生动物线粒体基因组在大小和基因含量上一直保持稳定,相比之下核基因组则发生了巨大的改变。后生动物线粒体基因组结构的可塑性在一定程度上归功于可能由tRNA基因介导的基因重排事件,虽然亲缘关系密切的物种间也可能出现基因重排,但同门内的线粒体基因组仍趋向于具有类似的结构特征。我们对后生动物线粒体基因组的起源、大小和基因排列进化方面的特点进行了介绍。     

The Putative Mitochondrial Genome of Plasmodium falciparum

Intraerythrocytic stages of mammalian malarial parasites employ glycolysis for energy production but some aspects of mitochondrial function appear crucial to their survival since inhibitors of mitochondrial protein synthesis and electron transport have antimalarial effects. Investigations of the putative mitochondrial genome of Plasmodium falciparum have detected organellar rRNAs and tRNAs encoded by a 35 kb circular DNA. Some features of the organization and sequence of the rRNA genes are reminiscent of chloroplast DNAs. The 35 kb DNA also encodes open reading frames for proteins normally found in chloroplast but not mitochondrial genomes. An apparently unrelated 6 kb tandemly repeated element which encodes two mitochondrial protein coding genes and fragments of rRNA genes is also found in malarial parasites. The malarial mitochondrial genome thus appears quite unusual. Further investigations are expected to provide insights into the possible functional relationships between these molecules and perhaps their evolutionary history.     

Age-Associated Alterations of the Mitochondrial Genome

Age-associated alterations of the mitochondrial genome occur in several different species; however, their physiological relevance remains unclear. The age-associated changes of mitochondrial DNA (mtDNA) include nucleotide point mutations and modifications, as well as deletions. In this review, we summarize the current literature on age-associated mtDNA mutations and deletions and comment on their abundance. A clear need exists for a more thorough evaluation of the total damage to the mitochondrial genome that accumulates in aged tissues. © 1997 Elsevier Science Inc.     

The Mitochondrial Genome of the Honeybee Apis Mellifera: Complete Sequence and Genome Organization

The complete sequence of honeybee (Apis mellifera) mitochondrial DNA is reported being 16,343 bp long in the strain sequenced. Relative to their positions in the Drosophila map, 11 of the tRNA genes are in altered positions, but the other genes and regions are in the same relative positions. Comparisons of the predicted protein sequences indicate that the honeybee mitochondrial genetic code is the same as that for Drosophila; but the anticodons of two tRNAs differ between these two insects. The base composition shows extreme bias, being 84.9% AT (cf. 78.6% in Drosophila yakuba). In protein-encoding genes, the AT bias is strongest at the third codon positions (which in some cases lack guanines altogether), and least in second codon positions. Multiple stepwise regression analysis of the predicted products of the protein-encoding genes shows a significant association between the numbers of occurrences of amino acids and %T in codon family, but not with the number of codons per codon family or other parameters associated with codon family base composition. Differences in amino acid abundances are apparent between the predicted Apis and Drosophila proteins, with a relative abundance in the Apis proteins of lysine and a relative deficiency of alanine. Drosophila alanine residues are as often replaced by serine as conserved in Apis. The differences in abundances between Drosophila and Apis are associated with %AT in the codon families, and the degree of divergence in amino acid composition between proteins correlates with the divergence in %AT at the second codon positions. Overall, transversions are about twice as abundant as transitions when comparing Drosophila and Apis protein-encoding genes, but this ratio varies between codon positions. Marked excesses of transitions over chance expectation are seen for the third positions of protein-coding genes and for the gene for the small subunit of ribosomal RNA. For the third codon positions the excess of transitions is adequately explained as due to the restriction of observable substitutions to transitions for conserved amino acids with two-codon families; the excess of transitions over expectation for the small ribosomal subunit suggests that the conservation of nucleotide size is favored by selection.     

On the Origin of Indonesian Cattle

Background

Two bovine species contribute to the Indonesian livestock, zebu (Bos indicus) and banteng (Bos javanicus), respectively. Although male hybrid offspring of these species is not fertile, Indonesian cattle breeds are supposed to be of mixed species origin. However, this has not been documented and is so far only supported by preliminary molecular analysis.

Methods and Findings

Analysis of mitochondrial, Y-chromosomal and microsatellite DNA showed a banteng introgression of 10–16% in Indonesian zebu breeds. East-Javanese Madura and Galekan cattle have higher levels of autosomal banteng introgression (20–30%) and combine a zebu paternal lineage with a predominant (Madura) or even complete (Galekan) maternal banteng origin. Two Madura bulls carried taurine Y-chromosomal haplotypes, presumably of French Limousin origin. In contrast, we did not find evidence for zebu introgression in five populations of the Bali cattle, a domestic form of the banteng.

Conclusions

Because of their unique species composition Indonesian cattle represent a valuable genetic resource, which potentially may also be exploited in other tropical regions.     

基于线粒体基因片段核苷酸多态性的亚洲栽培稻起源进化研究

亚洲栽培稻的祖先是普通野生稻,已成为世界公认的观点,然而亚洲栽培稻的2个亚种:粳稻和籼稻是一次起源还是二次起源仍存在很大争议,其起源地是国内还是国外依然是国际学者间争论的焦点。本文通过对184份亚洲栽培稻和203份普通野生稻3段基因序列cox3、cox1、orf 224和2段基因间序列ssv-39/178、rps2-trnfM的多样性研究,验证了以下观点:1)粳稻起源于中国,籼稻起源于中国和国外;2)亚洲栽培稻的起源为二次起源,即普通野生稻存在偏籼和偏粳2种类型,亚洲栽培稻的2个亚种籼稻和粳稻在进化过程中分别由偏籼型的普通野生稻和偏粳型的普通野生稻进化而来。     

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.     

The Mitochondrial Genome of Chlorogonium elongatum Inferred from the Complete Sequence

The 22,704-bp circular mitochondrial DNA (mtDNA) of the chlamydomonad alga Chlorogonium elongatum was completely cloned and sequenced. The genome encodes seven proteins of the respiratory electron transport chain, subunit 1 of the cytochrome oxidase complex (cox1), apocytochrome b (cob), five subunits of the NADH dehydrogenase complex (nad1, nad2, nad4, nad5, and nad6), a set of three tRNAs (Q, W, M), and the large (LSU)- and small (SSU)-subunit ribosomal RNAs. Six group-I introns were found, two each in the cox1, cob, and nad5 genes. In each intron an open reading frame (ORF) related to maturases or endonucleases was identified. Both the LSU and the SSU rRNA genes are split into fragments intermingled with each other and with other genes. Although the average A + T content is 62.2%, GC-rich clusters were detected in intergenic regions, in variable domains of the rRNA genes, and in introns and intron-encoded ORFs. A comparison of the genome maps reveals that C. elongatum and Chlamydomonas eugametos mtDNAs are more closely related to one another than either is to Chlamydomonas reinhardtii mtDNA. Received: 3 November 1997 / Accepted: 12 January 1998     

The Mitochondrial Genome of the Entomoparasitic Green Alga Helicosporidium

Background

Helicosporidia are achlorophyllous, non-photosynthetic protists that are obligate parasites of invertebrates. Highly specialized, these pathogens feature an unusual cyst stage that dehisces inside the infected organism and releases a filamentous cell displaying surface projections, which will penetrate the host gut wall and eventually reproduce in the hemolymph. Long classified as incertae sedis or as relatives of other parasites such as Apicomplexa or Microsporidia, the Helicosporidia were surprisingly identified through molecular phylogeny as belonging to the Chlorophyta, a phylum of green algae. Most phylogenetic analyses involving Helicosporidia have placed them within the subgroup Trebouxiophyceae and further suggested a close affiliation between the Helicosporidia and the genus Prototheca. Prototheca species are also achlorophyllous and pathogenic, but they infect vertebrate hosts, inducing protothecosis in humans. The complete plastid genome of an Helicosporidium species was recently described and is a model of compaction and reduction. Here we describe the complete mitochondrial genome sequence of the same strain, Helicosporidium sp. ATCC 50920 isolated from the black fly Simulium jonesi.

Methodology/Principal Findings

The circular mapping 49343 bp mitochondrial genome of Helicosporidium closely resembles that of the vertebrate parasite Prototheca wickerhamii. The two genomes share an almost identical gene complement and display a level of synteny that is higher than any other sequenced chlorophyte mitochondrial DNAs. Interestingly, the Helicosporidium mtDNA feature a trans-spliced group I intron, and a second group I intron that contains two open reading frames that appear to be degenerate maturase/endonuclease genes, both rare characteristics for this type of intron.

Conclusions/Significance

The architecture, genome content, and phylogeny of the Helicosporidium mitochondrial genome are all congruent with its close relationship to Prototheca within the Trebouxiophyceae. The Helicosporidium mitochondrial genome does, however, contain a number of novel features, particularly relating to its introns.     

广西华珊瑚蛇线粒体基因组全序列测定与分析

本研究对眼镜蛇科广西华珊瑚蛇（Sinomicrurus peinani）线粒体基因组序列进行测定与分析,并探究其与近缘种的系统发育关系。结果表明,广西华珊瑚蛇线粒体基因组是一条全长19 477 bp的环状DNA,基因组碱基构成为A（33.4%）、T（28.1%）、C（26.6%）和G（11.9%）。共编码38个基因,包含2个核糖体RNA（rRNA）基因、22个转移RNA（tRNA）基因、13个蛋白质编码基因及1个线粒体基因控制区（D-loop）。13个蛋白质编码基因均采用AUG作为起始密码子,UAA和UGA作为终止密码子;蛋白质编码基因编码频率较高的氨基酸分别为亮氨酸（Leu）、异亮氨酸（Ile）、苏氨酸（Thr）和丝氨酸（Ser）;相对密码子使用度（RSCU）频率最高的4个密码子依次是CGA、UGA、CUA和CCA。22个tRNA,除tRNASer（一臂两环）外其他均可形成典型三叶草结构。基于眼镜蛇科线粒体基因组系统发育分析结果表明,与广西华珊瑚蛇关系最密切的是中华珊瑚蛇（Sinomicrurus macclellandi）,其次是孟加拉眼镜蛇（Naja kaouthia）与眼镜王蛇（Ophiophagus hannah）。     

Unraveling Selection in the Mitochondrial Genome of Drosophila

We examine mitochondrial DNA variation at the cytochrome b locus within and between three species of Drosophila to determine whether patterns of variation conform to the predictions of neutral molecular evolution. The entire 1137-bp cytochrome b locus was sequenced in 16 lines of Drosophila melanogaster, 18 lines of Drosophila simulans and 13 lines of Drosophila yakuba. Patterns of variation depart from neutrality by several test criteria. Analysis of the evolutionary clock hypothesis shows unequal rates of change along D. simulans lineages. A comparison within and between species of the ratio of amino acid replacement change to synonymous change reveals a relative excess of amino acid replacement polymorphism compared to the neutral prediction, suggestive of slightly deleterious or diversifying selection. There is evidence for excess homozygosity in our world wide sample of D. melanogaster and D. simulans alleles, as well as a reduction in the number of segregating sites in D. simulans, indicative of selective sweeps. Furthermore, a test of neutrality for codon usage shows the direction of mutations at third positions differs among different topological regions of the gene tree. The analyses indicate that molecular variation and evolution of mtDNA are governed by many of the same selective forces that have been shown to govern nuclear genome evolution and suggest caution be taken in the use of mtDNA as a ``neutral' molecular marker.