The secondary structures of the Xenopus laevis and human mitochondrial small ribosomal subunit RNA are similar

AbstractExtensive corrections of the nucleotide sequence of the Xenopuslaevis mitochondrial small ribosomal subunit RNA gene [Roe et al. (1985) J. Biol. Chem. 260, 9759-9774] are reported. We found an additional fragment of 142 nucleotides and describe 25 nucleotide differences scattered in the gene. The nucleotide sequence of the X. laevis mitochondrial 12 S rRNA gene presents 80% homology with that of the same gene of bovine mitochondrion. We propose a new secondary structure for the product of the X. laevis gene. Contrary to the finding of Roe et al., we observed the same general organization of stems and loops as for the human mitochondrial 12 S rRNA gene product. On the other hand, the structural homology observed between the mitochondrial and cytoplasmic small subunit rRNAs of X. laevis appears much lower. These results strongly suggest that animal vertebrate mitochondrial DNAs have followed the same evolutionary pathway

Mendelian breeding units <i>versus</i> standard sampling strategies: mitochondrial DNA variation in southwest Sardinia

We report a sampling strategy based on Mendelian Breeding Units (MBUs), representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region) in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits

Chronic Progressive External Ophthalmoplegia Is Associated with a Novel Mutation in the Mitochondrial tRNA(Asn) Gene

Chronic progressive external ophthalmoplegia (CPEO) is caused by a decreased oxidative phosphorylation (OXPHOS) activity due to large-scale deletions of the mitochondrial genome in 50 % of the patients. The deletions encompass structural OXPHOS genes as well as tRNA genes, required for their expression so that the pathogenesis could be due to the deleted OXPHOS subunits or to an impaired mitochondrial translation. We have analyzed the mitochondrial genome of a patient presenting with CPEO for single base substitutions and discovered a novel heteroplasmic mutation in the tRNAAsn gene at position 5692 that converts a highly conserved adenine into a guanine. This mutation is unique because it is located at the transition of the anticodon loop to the anticodon stem and it leads to an additional base pair, thus reducing the number of loop-forming nucleotides from seven to five. Our findings suggest that CPEO can be caused by a single base substition in a mitochondrial tRNA gene so that the mitochondrial protein synthesis becomes the rate limiting step in OXPHOS fidelity

Role of mitochondria in Parkinson disease

The cause of the selective degeneration of nigrostriatal neurons in Parkinson disease (PD) has remained largely unknown. Exceptions include rare missense mutations in the alpha-synuclein gene on chromosome 4, a potentially pathogenic mutation affecting the ubiquitin pathway, and mutations in the parkin gene on chromosome 6. However, unlike classical PD, the latter syndrome is not associated with the formation of typical Lewy bodies. In contrast, a biochemical defect of complex I of the mitochondrial respiratory chain has been described in a relatively large group of confirmed PD cases. Recent cybrid studies indicate that the complex I defect in PD has a genetic cause and that it may arise from mutations in the mitochondrial DNA, Sequence analysis of the mitochondrial genome supports the view that mitochondrial point mutations are involved in PD pathogenesis. However, although mitochondria function as regulators in several known forms of cell death, their exact involvement in PD has remained unresolved. This is of relevance because classical apoptosis does not appear to play a major role in the degeneration of the parkinsonian nigra

Molecular phylogenetics and mitochondrial evolution

The myth of a "typical" mitochondrial genome (mtDNA) is a rock-hard belief in the field of genetics, at least for the animal kingdo

Mitochondrial DNA data of Cabo Verde Immigrant Population Living in Lisboa

Póster apresentado em 8 th International Y Chromosome User Workshop 5 th International EMPOP Meeting, Innsbruck, September 06-08, 2012Mitochondrial DNA (mtDNA) analysis found an important role in forensic genetics, especially when nuclear DNA analysis does not give a conclusive response. It is a powerful tool to exclude samples as originating from the same matriline. Features that increase the vested interest of mtDNA are the high copy number per cell, maternal inheritance, absence of recombination, and high mutation rate. Due to the higher overall mutation rate, the control region is comparatively enriched in sequence variation and therefore its analysis is important to establish haplotypes and haplogroups. Haplogroup assignment became noteworthy to clarify the history and demographic past of a population. As well as occurring all over Europe, in Portugal, and particularly in Lisboa, immigrant populations are increasing. The Instituto Nacional de Medicina Legal e Ciências Forenses is carrying out a comprehensive genetic study with the aim of portraying the genetic diversity of the immigrants who live in Lisboa. Within that objective, the present study intends to: obtain the mtDNA variability of Cabo Verde Immigrant Population Living in Lisboa and classify haplotypes into haplogroups. The studied population shows great interpopulation genetic variability due to the high frequency of unique haplotypes. Cabo Verde immigrants living in Lisboa exhibit haplotypes that belong to haplogroups observed in native Africans and in West Eurasian. MtDNA control region typing is extremely useful as a technique to differentiate among degraded samples frequently found in forensic genetics and to establish its global frequency when having knowledge of the genetic structure of populations.N/

mtDB: Human Mitochondrial Genome Database, a resource for population genetics and medical sciences

The mitochondrial genome, contained in the subcellular mitochondrial network, encodes a small number of peptides pivotal for cellular energy production. Mitochondrial genes are highly polymorphic and cataloguing existing variation is of interest for medical scientists involved in the identification of mutations causing mitochondrial dysfunction, as well as for population genetics studies. Human Mitochondrial Genome Database (mtDB) (http://www.genpat.uu.se/mtDB) has provided a comprehensive database of complete human mitochondrial genomes since early 2000. At this time, owing to an increase in the number of published complete human mitochondrial genome sequences, it became necessary to provide a web-based database of human whole genome and complete coding region sequences. As of August 2005 this database contains 2104 sequences (1544 complete genome and 560 coding region) available to download or search for specific polymorphisms. Of special interest to medical researchers and population geneticists evaluating specific positions is a complete list of (currently 3311) mitochondrial polymorphisms among these sequences. Recent expansions in the capabilities of mtDB include a haplotype search function and the ability to identify and download sequences carrying particular variant

mtDB: Human Mitochondrial Genome Database, a resource for population genetics and medical sciences

The mitochondrial genome, contained in the subcellular mitochondrial network, encodes a small number of peptides pivotal for cellular energy production. Mitochondrial genes are highly polymorphic and cataloguing existing variation is of interest for medical scientists involved in the identification of mutations causing mitochondrial dysfunction, as well as for population genetics studies. Human Mitochondrial Genome Database (mtDB) () has provided a comprehensive database of complete human mitochondrial genomes since early 2000. At this time, owing to an increase in the number of published complete human mitochondrial genome sequences, it became necessary to provide a web-based database of human whole genome and complete coding region sequences. As of August 2005 this database contains 2104 sequences (1544 complete genome and 560 coding region) available to download or search for specific polymorphisms. Of special interest to medical researchers and population geneticists evaluating specific positions is a complete list of (currently 3311) mitochondrial polymorphisms among these sequences. Recent expansions in the capabilities of mtDB include a haplotype search function and the ability to identify and download sequences carrying particular variants

The bacterial and mitochondrial ribosomal A-site molecular switches possess different conformational substates

The A site of the small ribosomal subunit participates in the fidelity of decoding by switching between two states, a resting ‘off’ state and an active decoding ‘on’ state. Eight crystal structures of RNA duplexes containing two minimal decoding A sites of the Homo sapiens mitochondrial wild-type, the A1555G mutant or bacteria have been solved. The resting ‘off’ state of the mitochondrial wild-type A site is surprisingly different from that of the bacterial A site. The mitochondrial A1555G mutant has two types of the ‘off’ states; one is similar to the mitochondrial wild-type ‘off’ state and the other is similar to the bacterial ‘off’ state. Our present results indicate that the dynamics of the A site in bacteria and mitochondria are different, a property probably related to the small number of tRNAs used for decoding in mitochondria. Based on these structures, we propose a hypothesis for the molecular mechanism of non-syndromic hearing loss due to the mitochondrial A1555G mutation