Sequence analysis of cDNAs for the human and bovine ATP synthase β subunit: mitochondrial DNA genes sustain seventeen times more mutations

We have cloned and sequenced human and bovine cDNAs for the subunit of the ATP synthase (ATP-synß), a nuclear DNA (nDNA) encoded oxidative phosphorylation (OXPHOS) gene. The two cDNAs were found to share 99% amino acid homology and 94% nucleotide homology. The evolutionary rate of ATPsynß was then compared with that of two mitochondrial DNA (mtDNA) ATP synthase genes (ATPase 6 and 8), seven other mtDNA OXPHOS genes, and a number of nuclear genes. The synonymous substitution rate for ATPsynß proved to be 1.9 × 10^–9 substitutions per site per year (substitutions × site^–1 × year^–1) (SSY). This is less than 1/2 that of the average nDNA gene, 1/12 the rate of ATPase 6 and 8, and 1/17 the rate of the average mtDNA gene. The synonymous and replacement substitution rates were used to calculate a new parameter, the selective constraint ratio. This revealed that even the most variable mtDNA protein was more constrained than the average nDNA protein. Thus, the high substitution mutation rate and strong selective constraints of mammalian mtDNA proteins suggest that mtDNA mutations may result in a disproportionately large number of human hereditary diseases of OXPHOS.     

Presence of a linear plasmid-like DNA molecule in the fungal pathogen Ceratocystis fimbriata Ell. & Halst.

Summary A plasmid-like molecule was detected in a strain of the ascomycete Ceratocystis fimbriata Ell. & Halst., a pathogenic fungus of Populus spp. The DNA replicon, designated pFQ501, was found to have a linear structure with a length of 6.0 kb (3.9 × 10⁶ daltons) and a density of 1.685 g/cc. This molecule was found to be associated with the mitochondria and was isolated from the gel; its restriction map was deduced from single and double digestions.     

Location,identity, amount and serial entry of chloroplast DNA sequences in crucifer mitochondrial DNAs

Southern blot hybridization techniques were used to examine the chloroplast DNA (cpDNA) sequences present in the mitochondrial DNAs (mtDNAs) of two Brassica species (B. campestris and B. hirta), two closely related species belonging to the same tribe as Brassica (Raphanus sativa, Crambe abyssinica), and two more distantly related species of crucifers (Arabidopsis thaliana, Capsella bursa-pastoris). The two Brassica species and R. sativa contain roughly equal amounts (12–14 kb) of cpDNA sequences integrated within their 208–242 kb mtDNAs. Furthermore, the 11 identified regions of transferred DNA, which include the 5 end of the chloroplast psaA gene and the central segment of rpoB, have the same mtDNA locations in these three species. Crambe abyssinica mtDNA has the same complement of cpDNA sequences, plus an additional major region of cpDNA sequence similarity which includes the 16S rRNA gene. Therefore, except for the more recently arrived 16S rRNA gene, all of these cpDNA sequences appear to have entered the mitochondrial genome in the common ancestor of these three genera. The mitochondrial genomes of A. thaliana and Capsella bursa-pastoris contain significantly less cpDNA (5–7 kb) than the four other mtDNAs. However, certain cpDNA sequences, including the central portion of the rbcL gene and the 3 end of the psaA gene, are shared by all six crucifer mtDNAs and appear to have been transferred in a common ancestor of the crucifer family over 30 million years ago. 1n conclusion, DNA has been transferred sequentially from the chloroplast to the mitochondrion during crucifer evolution and these cpDNA sequences can persist in the mitochondrial genome over long periods of evolutionary time.     

Pattern of mtDNA Variation in Three Populations from São Tomé e Príncipe

We have analysed the matrilineal genetic composition of three self‐reported ethnic groups from São Tomé e Príncipe (Gulf of Guinea), an African archipelago whose settlement begun in the late fifteenth century. Sequence data from the hypervariable segments I (HVS‐I) and II (HVS‐II) were obtained for 30 Angolares, 35 Forros and 38 Tongas. The repertory of mtDNA lineages in São Tomé e Príncipe denoted a fully African maternal pool, primarily arisen from a Central/Southwestern substratum. The absence of any lineages of putative European descent means that the European impact at the mitochondrial pool was virtually nil. Angolares showed a clear reduction of mtDNA diversity and a slight genetic differentiation relative to Tongas or Forros, whereas the latter two groups did not present any signs of genetic boundaries between each other. The data obtained here reinforce the depiction of genetic substructuring in São Tomé e Príncipe previously derived from Y‐chromosome STRs. In addition, the crossing of mtDNA and Y‐STR information led to the inference that the female mediated gene flow within the archipelago was less restricted than the male, a pattern that could be framed in the cultural traditions and socio‐historical interactions among the groups.     

Mitochondrial DNA and Y-Chromosome Variation in the Caucasus

We have analyzed mtDNA HVI sequences and Y chromosome haplogroups based on 11 binary markers in 371 individuals, from 11 populations in the Caucasus and the neighbouring countries of Turkey and Iran. Y chromosome haplogroup diversity in the Caucasus was almost as high as in Central Asia and the Near East, and significantly higher than in Europe. More than 27% of the variance in Y‐haplogroups can be attributed to differences between populations, whereas mtDNA showed much lower heterogeneity between populations (less then 5%), suggesting a strong influence of patrilocal social structure. Several groups from the highland region of the Caucasus exhibited low diversity and high differentiation for either or both genetic systems, reflecting enhanced genetic drift in these small, isolated populations. Overall, the Caucasus groups showed greater similarity with West Asian than with European groups for both genetic systems, although this similarity was much more pronounced for the Y chromosome than for mtDNA, suggesting that male‐mediated migrations from West Asia have influenced the genetic structure of Caucasus populations.     

Y Chromosome and Mitochondrial DNA Characterization of Pasiegos, a Human Isolate from Cantabria (Spain)

Mitochondrial DNA sequences and Y chromosome haplotypes were characterized in Pasiegos, a human isolate from Cantabria, and compared with those of other Cantabrian and neighbouring Northern Spain populations. Cantabria appears to be a genetically heterogeneous community. Whereas Lebaniegos do not differ from their eastern Basque and western Asturian and Galician neighbours, Pasiegos and other non‐Lebaniego Cantabrians show significant differences with all of them. Pasiegos are peculiar for their high frequencies of Y chromosomal markers (E‐M81) with North African assignation, and Y chromosomal (R‐SRY2627) and mtDNA (V, I, U5) markers related to northern European populations. This dual geographic contribution is more in agreement with the complex demographic history of this isolate, as opposed to recent drift effects. The high incidence in Cantabrians with pre‐V and V mtDNA haplotypes, considered as a signal of Postglacial recolonization in Europe from south‐western refugees, points to such refugees as a better candidate population than Basques for this expansion. However, this does not discount a conjoint recolonization.     

中国Leber遗传性视神经病变14484位点突变的家系分析

目的:了解我国Leber遗传性视神经病变(Leber’shereditaryopticneuropathy,LHON)线粒体DNA(mtDNA)14484位点突变患者的发病率和临床特征。方法:对来自117个家系的119例临床确诊或疑诊LHON的患者进行mtDNA检测。对3例证实为14484位点突变的家系做深入调查并收集相关病史及临床资料,抽取15例家属的血样进行mtDNA检测。结果:存在线粒体DNA突变的62例(62/119,52.1%)中,14484位点突变仅3例(4.8%)。该3例3个家系56例中,28例有眼部症状,外显率50%。发病经过和临床表现类似11778位点突变的LHON,但其中视力恢复者17例(60.7%)。15例家属的血样检测再次证实为14484位点突变。结论:我国LHON患者中14484位点突变者少见,其临床表现与11778位点突变者相似,惟视力恢复率高。     

Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.     

盆腔器官脱垂患者外周血和盆底组织中mtDNA和mtDNA~(4977)的含量及意义

目的:探讨盆腔器官脱垂(POP)患者外周血和盆底不同组织中线粒体DNA(mtDNA)及mtDNA 4977bp缺失(mtDNA4977)的含量变化与POP发生发展之间的关系。方法:采用实时定量PCR法分别检测26例POP患者和21例非POP患者外周血、骶韧带、阴道前后壁组织中mtDNA和mtDNA4977的相对含量。结果:(1)mtDNA在骶韧带中的含量,POP组明显低于非POP组,差异有统计学意义(P<0.05);而mtDNA在POP患者的外周血、阴道前壁和后壁中的含量,与非POP组比较,差异均无统计学意义(P>0.05)。mtDNA4977在POP患者的外周血、骶韧带、阴道前壁和后壁中的含量均显著高于非POP患者,差异有统计学意义(P<0.05)。无论mtDNA还是mtDNA4977,其含量在阴道前壁和后壁之间均无显著差异(P>0.05)。(2)随着POP程度不断加重(分析0到Ⅲ期POP),发现骶韧带中mtDNA含量呈下降趋势,而外周血、阴道前壁和后壁中此趋势不明显;在外周血、骶韧带、阴道前壁和后壁中mtDNA4977的比例却显著增加(P<0.05)。(3)POP患者外周血、骶韧带及阴道壁中mtDNA与mtDNA4977含量均无明显相关性(P>0.05)。mtDNA在POP患者外周血和骶韧带之间呈正相关(P<0.05),而mtDNA4977在POP患者外周血和骶韧带之间无显著相关性(P>0.05)。结论:mtDNA的消耗和mtDNA4977比例增加可能在POP分子水平的发病机制中起重要作用。