High-Throughput Detection of mtDNA Mutations Leading to tRNA Processing Errors.

Some mutations in the tRNA genes of mitochondrial DNA (mtDNA) have been demonstrated to affect the processing of the mitochondrial transcriptome in human patients with mitochondrial disease. A recent analysis of mtDNA mutations in 527 human tumors revealed that approximately a quarter of the somatic mt-tRNA gene mutations lead to aberrant processing of the mitochondrial transcriptome in these tumors. Here, we describe a method, based on mtDNA mutations induced by the mtDNA mutator mouse, to map the sites that lead to transcript processing abnormalities.

Current progress with mammalian models of mitochondrial DNA disease.

Mitochondrial disorders make up a large class of heritable diseases that cause a broad array of different human pathologies. They can affect many different organ systems, or display very specific tissue presentation, and can lead to illness either in childhood or later in life. While the over 1200 genes encoded in the nuclear DNA play an important role in human mitochondrial disease, it has been known for over 30 years that mutations of the mitochondria's own small, multicopy DNA chromosome (mtDNA) can lead to heritable human diseases.

Increased Total mtDNA Copy Number Cures Male Infertility Despite Unaltered mtDNA Mutation Load.

Mutations of mtDNA cause mitochondrial diseases and are implicated in age-associated diseases and aging. Pathogenic mtDNA mutations are often present in a fraction of all mtDNA copies, and it has been widely debated whether the proportion of mutant genomes or the absolute number of wild-type molecules determines if oxidative phosphorylation (OXPHOS) will be impaired. Here, we have studied the male infertility phenotype of mtDNA mutator mice and demonstrate that decreasing mtDNA copy number worsens mitochondrial aberrations of spermatocytes and spermatids in testes, whereas an increase in mtDNA copy number rescues the fertility phenotype and normalizes testes morphology as well as spermatocyte proteome changes.

Insect mitochondrial genomics 3: the complete mitochondrial genome sequences of representatives from two neuropteroid orders: a dobsonfly (order Megaloptera) and a giant lacewing and an owlfly (order Neuroptera).

We describe the complete mitochondrial genomes from representatives of two orders of the Neuropterida: a dobsonfly, Corydalus cornutus (Megaloptera: Corydalidae, GenBank Accession No. FJ171323), a giant lacewing Polystoechotes punctatus (Neuroptera: Polystoechotidae, FJ171325), and an owlfly, Ascaloptynx appendiculatus (Neuroptera: Ascalaphidae, FJ171324). The dobsonfly sequence is 15,687 base pairs with a major noncoding (A+T rich) region of approximately 967 bp.

Purifying selection of mtDNA and its implications for understanding evolution and mitochondrial disease.

Mutations of mitochondrial DNA (mtDNA) are frequent in humans and are implicated in many different types of pathology. The high substitution rate and the maternal, asexual mode of transmission of mtDNA make it more likely to accumulate deleterious mutations. Here, we discuss recent evidence that mtDNA transmission is subject to strong purifying selection in the mammalian female germ line, limiting the accumulation of such mutations.

Strong purifying selection in transmission of mammalian mitochondrial DNA.

There is an intense debate concerning whether selection or demographics has been most important in shaping the sequence variation observed in modern human mitochondrial DNA (mtDNA). Purifying selection is thought to be important in shaping mtDNA sequence evolution, but the strength of this selection has been debated, mainly due to the threshold effect of pathogenic mtDNA mutations and an observed excess of new mtDNA mutations in human population data. We experimentally addressed this issue by studying the maternal transmission of random mtDNA mutations in mtDNA mutator mice expressing a proofreading-deficient mitochondrial DNA polymerase.

Insect mitochondrial genomics 2: The complete mitochondrial genome sequence of a giant stonefly, Pteronarcys princeps, asymmetric directional mutation bias, and conserved plecopteran A+T-region elements.

Mitochondrial (mt) genome sequences of insects are receiving renewed attention in molecular phylogentic studies, studies of mt-genome rearrangement, and other unusual molecular phenomena, such as translational frameshifting. At present, the basal neopteran lineages are poorly represented by mt-genome sequences. Complete mt-genome sequences are available in the databases for only the Orthoptera and Blatteria; 9 orders are unrepresented.

Insect mitochondrial genomics: the complete mitochondrial genome sequence of the meadow spittlebug Philaenus spumarius (Hemiptera: Auchenorrhyncha: Cercopoidae).

We present the complete mitochondrial genome sequence of the meadow spittlebug Philaenus spumarius (Auchenorrhyncha: Cercopoidae). This contribution represents the second mitochondrial genome from the Hemiptera and the second of the three hemipteran suborders sampled. The genome is a circular molecule of 16 324 bp with a total A+T content of 77.

Phylogenetic and genomic analysis of the complete mitochondrial DNA sequence of the spotted asparagus beetle Crioceris duodecimpunctata.

We report the complete mitochondrial DNA sequence of the spotted asparagus beetle, Crioceris duodecimpunctata. The genome complement, gene order, and nucleotide composition of this beetle's mitochondrial genome were found to be typical of those reported for other insects. Unusual features of this genome include the substitution of UCU for GCU as the anticodon for tRNA(Ser), an unusual TpsiC loop for the tRNA(Ile) gene, and the identification of a putative ATT start codon for cox1.