Sequence analysis of the complete mitochondrial DNA in 10 commonly used inbred rat strains

Abstract

quence analysis of the complete mitochondrial DNA in 10 commonly used inbred rat strains. Am J Physiol Cell Physiol 291: C1183-C1192, 2006. First published July 19, 2006 doi:10.1152/ajpcell.00234.2006.-Rat remains a major biomedical model system for common, complex diseases. The rat continues to gain importance as a model system with the completion of its full genomic sequence. Although the genomic sequence has generated much interest, only three complete sequences of the rat mitochondria exist. Therefore, to increase the knowledge of the rat genome, the entire mitochondrial genomes (16,307-16,315 bp) from 10 inbred rat strains (that are standard laboratory models around the world) and 2 wild rat strains were sequenced. We observed a total of 195 polymorphisms, 32 of which created an amino acid change (nonsynonymous substitutions) in 12 of the 13 protein coding genes within the mitochondrial genome. There were 11 single nucleotide polymorphisms within the tRNA genes, six in the 12S rRNA, and 12 in the 16S rRNA including 3 insertions/deletions. We found 14 single nucleotide polymorphisms and 2 insertion/deletion polymorphisms in the D-loop. The inbred rat strains cluster phylogenetically into three distinct groups. The wild rat from Tokyo grouped closely with five inbred strains in the phylogeny, whereas the wild rat from Milwaukee was not closely related to any inbred strain. These data will enable investigators to rapidly assess the potential impact of the mitochondria in these rats on the physiology and the pathophysiology of phenotypes studied in these strains. Moreover, these data provide information that may be useful as new animal models, which result in novel combinations of nuclear and mitochondrial genomes, are developed. genome; mitochondria MITOCHONDRIA ARE THE ONLY organelles (other than the nucleus) with their own DNA, which is maternally inherited (31, 36). The mammalian mitochondrial DNA (mtDNA) is a circular, double-stranded DNA that lacks introns and has only ϳ7% noncoding sequences (23) in contrast to the genomic DNA. The mtDNA encodes 37 genes, including 13 protein-coding genes that, in conjunction with subunits encoded by the nuclear genome, form the electron transport chain, the primary ATP producer for the cell. Also included within these 37 coding genes are 22 tRNA genes whose function is to transport amino acids to the ribosome and match them to the codons of the mRNAs thus facilitating incorporation of amino acids into the growing polypeptide during translation. The final 2 genes are rRNA genes. The D-loop or control region, although noncoding, contains binding sites for two transcription factors, three conserved sequence blocks (CSBs) associated with initiation of replication and the loop strand termination associated sequences (9,21,23,61

Genetic loci for bone architecture determined by three-dimensional CT in crosses with the diabetic GK rat

“…Genomic imprinting could be a possible explanation to the observed reciprocal effect due to its parent-of-origin specific inheritance. However, the more than 100 variant positions that have been identified in GK mtDNA compared to F344 [25], support the involvement of mtDNA as a major factor behind the observed reciprocal cross effect.…”

“…The more than 100 variant positions between GK and F344 mtDNA, including twelve non-synonymous amino acid changes in proteins required for ATP synthesis [25], support the involvement of mtDNA variants as a major factor behind the reciprocal cross effect.…”

Mitochondrial DNA Variant for Complex I Reveals a Role in Diabetic Cardiac Remodeling

“…Genetic analysis indicated that the two major differences between GK and T2DN are passenger loci (3%) and mtDNA (4). Specific sequence analysis of mtDNA showed that the T2DN rats carry mitochondria from FHH, whereas the GK carries mitochondria from Wistar Kyoto (WKY/NCrl) rats (5). To better understand the relationship between different mtDNA genomes and phenotypical manifestations in the setting of diabetes, we transferred the mitochondrial genome from GK to T2DN rats.…”

Aging Influences Cardiac Mitochondrial Gene Expression and Cardiovascular Function following Hemorrhage Injury

“…The 13 proteins on the mitochondrial DNA are: seven subunits of NADH dehydrogenase, cytochrome b, three cytochrome c oxidase subunits (1, 2 and 3), and ATP synthase 6 and 8. The gene sequences representing the rat mitochondrial genome included in the gene chip encompassed published mtDNA sequences of ten different inbred strains: WKY/NCrl (Wistar Kyoto; Accession # DQ673907); BN/NHsdMcwi (Brown Norway; Accession # AC_000022); F344/NHsd (Fisher 344; Accession # DQ673909); ACI/Eur (August × Copenhagen Irish; Accession # DQ673908); FHH/Eur (fawn hooded hypertensive; Accession # DQ673910); GK/Swe (Accession # DQ673913); GK/Far (Accession # DQ673912); T2DN/Mcwi (Accession # DQ673915); GH/OmrMcwi (Accession # DQ673911) and SS/JrHsdMcwi (Dahl Salt-sensitive; Accession # DQ673914) (17). These specific strains were chosen because complete sequences of mtDNA were available for each of them.…”