Tandemly repeated sequences in mtDNA control region of whitefish, Coregonus lavaretus

Genome ◽  
2000 ◽  
Vol 43 (3) ◽  
pp. 584-587 ◽  
Author(s):  
Pawel Brzuzan
Keyword(s):  
Mitochondrial Dna ◽  
Control Region ◽  
Pcr Amplification ◽  
Repeated Sequences ◽  
Coregonus Lavaretus ◽  
Length Variation ◽  
Conserved Sequence ◽  
Repeat Units ◽  
Pcr Products ◽  
D Loop

Length variation of the mitochondrial DNA control region was observed with PCR amplification of a sample of 138 whitefish (Coregonus lavaretus). Nucleotide sequences of representative PCR products showed that the variation was due to the presence of an approximately 100-bp motif tandemly repeated two, three, or five times in the region between the conserved sequence block-3 (CSB-3) and the gene for phenylalanine tRNA. This is the first report on the tandem array composed of long repeat units in mitochondrial DNA of salmonids.Key words: Coregonus lavaretus, D-loop mitochondrial DNA, tandemly repeated sequences.

scholarly journals Evolution of Repeated Sequence Arrays in the D-Loop Region of Bat Mitochondrial DNA

Genetics ◽  
1997 ◽  
Vol 146 (3) ◽  
pp. 1035-1048 ◽  
Author(s):  
Gerald S Wilkinson ◽  
Frieder Mayer ◽  
Gerald Kerth ◽  
Barbara Petri
Keyword(s):  
Mitochondrial Dna ◽  
Control Region ◽  
Tandem Repeats ◽  
Repeated Sequence ◽  
Repeat Number ◽  
Repeat Units ◽  
Loop Region ◽  
Control Region Sequences ◽  
Number Comparison ◽  
D Loop

Analysis of mitochondrial DNA control region sequences from 41 species of bats representing 11 families revealed that repeated sequence arrays near the tRNA-Pro gene are present in all vespertilionine bats. Across 18 species tandem repeats varied in size from 78 to 85 bp and contained two to nine repeats. Heteroplasmy ranged from 15% to 63%. Fewer repeats among heteroplasmic than homoplasmic individuals in a species with up to nine repeats indicates selection may act against long arrays. A lower limit of two repeats and more repeats among heteroplasmic than homoplasmic individuals in two species with few repeats suggests length mutations are biased. Significant regressions of heteroplasmy, θ and π, on repeat number further suggest that repeat duplication rate increases with repeat number. Comparison of vespertilionine bat consensus repeats to mammal control region sequences revealed that tandem repeats of similar size, sequence and number also occur in shrews, cats and bighorn sheep. The presence of two conserved protein-binding sequences in all repeat units indicates that convergent evolution has occurred by duplication of functional units. We speculate that D-loop region tandem repeats may provide signal redundancy and a primitive repair mechanism in the event of somatic mutations to these binding sites.

scholarly journals Protein binding to a single termination-associated sequence in the mitochondrial DNA D-loop region.

1993 ◽  
Vol 13 (4) ◽  
pp. 2162-2171 ◽  
Author(s):  
C S Madsen ◽  
S C Ghivizzani ◽  
W W Hauswirth
Keyword(s):  
Mitochondrial Dna ◽  
Protein Binding ◽  
Loop Formation ◽  
Sequence Element ◽  
Conserved Sequence ◽  
Loop Region ◽  
In Organello ◽  
Close Proximity ◽  
D Loop

A methylation protection assay was used in a novel manner to demonstrate a specific bovine protein-mitochondrial DNA (mtDNA) interaction within the organelle (in organello). The protected domain, located near the D-loop 3' end, encompasses a conserved termination-associated sequence (TAS) element which is thought to be involved in the regulation of mtDNA synthesis. In vitro footprinting studies using a bovine mitochondrial extract and a series of deleted mtDNA templates identified a approximately 48-kDa protein which binds specifically to a single TAS element also protected within the mitochondrion. Because other TAS-like elements located in close proximity to the protected region did not footprint, protein binding appears to be highly sequence specific. The in organello and in vitro data, together, provide evidence that D-loop formation is likely to be mediated, at least in part, through a trans-acting factor binding to a conserved sequence element located 58 bp upstream of the D-loop 3' end.

Biological Significance and Profile of Length Heteroplasmy in the Hypervariable Segments of the Human Mitochondrial DNA Control Regions from Blood Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3815-3815
Author(s):  
Myung-Geun Shin ◽  
Hyeoung-Joon Kim ◽  
Hye-Ran Kim ◽  
Hee-Nam Kim ◽  
Il-Kwon Lee ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Control Region ◽  
Blood Cells ◽  
Biological Significance ◽  
Length Heteroplasmy ◽  
Conserved Sequence ◽  
Healthy Donors ◽  
Mtdna Sequence ◽  
Mtdna Replication ◽  
Two Peaks

Abstract A high incidence of mitochondrial DNA (mtDNA) variations was observed in both hypervariable region (HV) 1 and HV2; most mtDNA sequence variations were localized at poly C tract at nucleotides (nt) 303-315 (CCCCCCCTCCCCC, 7CT5C) in the HV2. Another poly C tract variant in HV1 at nt 16184-6193 have been suggested to be related with diabetes, dilated cardiomyopathy and some cancers. Poly C tract in HV2 is part of the conserved sequence block II located in 92-bp from the heavy strand replication origin. It is not yet clear whether poly C variants at nt 303–315 would lead to alterations in mtDNA replication. We hypothesized that some severe alterations in poly C tracts may lead to impairment of mtDNA replication. Here we present the profile of length heteroplasmy in HV from blood cells and its biological significance. A total of 57 maternally unrelated healthy donors were included and heparinized bloods were obtained from five age groups including 12 cord bloods. We amplified and sequenced the 1,121-bp control region including HV1 and HV2. In an attempt to investigate mtDNA length heteroplasmy, we carried out a qualitative and quantitative profiling length heteroplasmy using size-based PCR product separation by capillary electrophoresis (ABI 3100 Genetic Analyzer and ABI Prism Genotyper version 3.1). Length heteroplasmy was further confirmed by cloning and sequencing. Quantitative analysis of mtDNA molecules was performed using the QuantiTect SYBR Green PCR kit (Qiagen) and Rotor-Gene 3000 (Corbett Research) and standard plot was obtained from cloned cytochrome b gene. The mtDNA control region sequences showed 57 different haplotypes resulting from 77 polymorphic positions. Common polymorphisms were 73A>G (98%), 263A>G (91%), 16223C>T (47%), 16189T>C (35%), 150C>T (25%) and 152T>C (18%). The patterns of length heteroplasmy in the HV2 region were classified into 6 types. In the HV1 region, length heteroplasmy showed 8 variant peak patterns. The distribution of length heteroplasmy in poly C tracts at nt 303 – 315 was mtDNA mixture of 7CT6C+8CT6C (53%), 8CT6C+9CT6C (26%), 8CT6C+9CT6C+10CT6C (11%), 9CT6C+10CT6C +11CT6C (5%), 9CT6C+10CT6C (3%) and 7CT6C+6CT6C (2%). The distribution of length heteroplasmy pattern in poly C tract at nt 16184 – 16193 was 5CT4C+5CT3C (60%), 9C+10C+11C+12C (21%), 9C+10C+11C (5%), 3CT6C+3CT5C (3%), 9C+10C+11C+12C+13C (3%), 3CT4C+3CT3C (3%), 10C+11C+12C (2%), and 8C+9C+10C+11C+12C (2%). Interestingly, this study revealed that all healthy subjects showed length heteroplasmy in the HV1 and HV2 regions in contrast to previous studies. Length heteroplasmy in poly C 303–315 showed two groups of two peaks (n = 48) and more than three peaks (n = 9). MtDNA content from group with three peaks in poly C 303–315 (61,983,373 molecules/ul ± 33,219,871, mean±SD) was markedly lower than those with two peaks (133,777,955 molecules/ul ± 87,209,377). In conclusion, significantly higher rate of length heteroplasmy was observed in HV1 and HV2 from healthy donors and the presence of more than three mtDNA types in poly C at nt 303 – 315 might be associated with impairment of mtDNA replication.

Profound Length Heteroplasmic Alterations in Mitochondrial DNA Control Region From Primary AML Cells: Implication of Impaired Mitochondrial Replication and Demonstration of ‘vicious cycle’ Hypothesis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3116-3116
Author(s):  
Myung-Geun Shin ◽  
Hye Ran Kim ◽  
Hyeoung-Joon Kim ◽  
Hoon Kook ◽  
Tai Ju Hwang ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Control Region ◽  
Copy Number ◽  
Regulatory Region ◽  
Mtdna Control Region ◽  
Vicious Cycle ◽  
Mtdna Copy Number ◽  
Length Heteroplasmy ◽  
Region Length ◽  
D Loop

Abstract Abstract 3116 Poster Board III-53 Mitochondrial DNA (mtDNA) control region (displacement (D)-loop including HV1 and HV2) is a non-coding region of 1124 bp (nucleotide positions, np 16 024–576), which acts as a promoter for both the heavy and light strands of mtDNA, and contains essential transcription and replication elements (Blood 2004;103:4466-77). Importantly, mutations in the D-loop regulatory region might change mtDNA replication rate by modifying the binding affinity of significant trans-activating factors (Eur J Cancer 2004;40:2519-24). Thus, length heteroplasmic alterations of mtDNA control region may be related with mitochondrial dysfunction resulting in ‘vicious cycle’ (Mol Med Today 2000;6:425-32). In an attempt to investigate profiling of mtDNA length heteroplasmic alterations in primary AML cells, we carried out a quantitative size-based PCR product separation by capillary electrophoresis (ABI 3130XL Genetic Analyzer and ABI Prism Genotyper version 3.1) using six targets (np 303-315 poly C, np 16184-16193 poly C, np 514-511 CA repeats, np 3566-3572 poly C, np 12385-12391 poly C and np 12418-12426 poly A). Length heteroplasmy was further confirmed by cloning and sequencing. Quantitative analysis of mtDNA molecules was performed using the QuantiTect SYBR Green PCR kit (Qiagen) and Rotor-Gene 3000 (Corbett Research). Forty-eight AML bone marrow samples were collected after receiving Institutional Review Board approval and informed consent. There were profound alterations of mtGI in 303 poly C, 16184 poly C and 514 CA repeats. The length heteroplasmy pattern of 303 poly C tract in the HV2 region disclosed mixture of 7C, 8C, 9C and 10C mtDNA types. In the HV2 region, length heteroplasmy in poly-C tract at np 303 - 309 exhibited 5 variant peak patterns: 7CT6C+8CT6C (50.0%), 8CT6C+9CT6C (14.0%), 8CT6C+ 9CT6C+ 10CT6C (10.4%), 9CT6C+10CT6C+11CT6C (8.3%) 9CT6C + 10CT6C + 11CT6C+12CT6C (2.1%). The length heteroplasmy pattern of 514-523 CA repeats in the HV2 region exhibited 2 variant peak patterns: CACACACACA (56.3%) and CACACACA (43.7%). In the HV1 region, length heteroplasmy in the poly-C tract at np 16184 - 16193 exhibited 9 variant peak patterns: 5CT4C+5CT3C (31.0%), 6CT4C+6CT3C (2.1%), 9C+10C+11C+12C (16.7%), 9C+10C+11C (2.1%), T4CT4C+5CT3C (4.2%), 9C+10C+11C+12C+13C (2.1%), 3CTC4C+5CT3C (2.1%), 10C+11C+12C+13C (4.2%), 8C+9C+10+11C (2.1%). Primary AML cells revealed decreased enzyme activity in respiratory chain complex I, II and III. AML cells had about a two-fold decrease in mtDNA copy number compared with normal blood mononuclear cells. Current study demonstrates that profound length heteroplasmic alterations in mtDNA control region of primary AML cells may lead to impairment of mitochondrial biogenesis (reduction of mtDNA copy number) and derangement of mitochondrial ATP synthesis. During this perturbation, mitochondria in primary AML cells might produce a large amount of reactive oxygen species, which causes the vicious cycle observed in chronic inflammatory diseases and cancers as well. Disclosures No relevant conflicts of interest to declare.

scholarly journals Detection of somatic mutations in the mitochondrial DNA control region D‑loop in brain tumors: The first report in Malaysian patients

2017 ◽  
Author(s):  
Abdul Mohamed Yusoff ◽  
Khairol Mohd Nasir ◽  
Khalilah Haris ◽  
Siti Mohd Khair ◽  
Abdul Abdul Ghani ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Brain Tumors ◽  
Control Region ◽  
Somatic Mutations ◽  
Mitochondrial Dna Control Region ◽  
First Report ◽  
D Loop

scholarly journals Pathological ribonuclease H1 causes R-loop depletion and aberrant DNA segregation in mitochondria

2016 ◽  
Vol 113 (30) ◽  
pp. E4276-E4285 ◽  
Author(s):  
Gokhan Akman ◽  
Radha Desai ◽  
Laura J. Bailey ◽  
Takehiro Yasukawa ◽  
Ilaria Dalla Rosa ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Control Region ◽  
Mitochondrial Disease ◽  
Genetic Information ◽  
Disease Mechanism ◽  
Dna Segregation ◽  
D Loop ◽  
Mitochondrial Dna Replication ◽  
Pathological Variant ◽  
Potential Substrate

The genetic information in mammalian mitochondrial DNA is densely packed; there are no introns and only one sizeable noncoding, or control, region containing key cis-elements for its replication and expression. Many molecules of mitochondrial DNA bear a third strand of DNA, known as “7S DNA,” which forms a displacement (D-) loop in the control region. Here we show that many other molecules contain RNA as a third strand. The RNA of these R-loops maps to the control region of the mitochondrial DNA and is complementary to 7S DNA. Ribonuclease H1 is essential for mitochondrial DNA replication; it degrades RNA hybridized to DNA, so the R-loop is a potential substrate. In cells with a pathological variant of ribonuclease H1 associated with mitochondrial disease, R-loops are of low abundance, and there is mitochondrial DNA aggregation. These findings implicate ribonuclease H1 and RNA in the physical segregation of mitochondrial DNA, perturbation of which represents a previously unidentified disease mechanism.

Length Variation in HV2 of the Human Mitochondrial DNA Control Region

2001 ◽  
Vol 46 (4) ◽  
pp. 15059J ◽  
Author(s):  
John E. B. Stewart ◽  
Constance L. Fisher ◽  
Patricia J. Aagaard ◽  
Mark R. Wilson ◽  
Alice R. Isenberg ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Control Region ◽  
Length Variation ◽  
Mitochondrial Dna Control Region ◽  
Human Mitochondrial Dna

scholarly journals Heteroplasmy of short tandem repeats in mitochondrial DNA of Atlantic cod, Gadus morhua.

Genetics ◽  
1992 ◽  
Vol 132 (1) ◽  
pp. 211-220 ◽  
Author(s):  
E Arnason ◽  
D M Rand
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Gadus Morhua ◽  
Tandem Repeats ◽  
Atlantic Cod ◽  
Length Variation ◽  
The North ◽  
Loop Region ◽  
D Loop ◽  
Displacement Model

Abstract The mitochondrial DNA of the Atlantic cod (Gadus morhua) contains a tandem array of 40-bp repeats in the D-loop region of the molecule. Variation among molecules in the copy number of these repeats results in mtDNA length variation and heteroplasmy (the presence of more than one form of mtDNA in an individual). In a sample of fish collected from different localities around Iceland and off George's Bank, each individual was heteroplasmic for two or more mtDNAs ranging in repeat copy number from two (common) to six (rare). An earlier report on mtDNA heteroplasmy in sturgeon (Acipenser transmontanus) presented a competitive displacement model for length mutations in mtDNAs containing tandem arrays and the cod data deviate from this model. Depending on the nature of putative secondary structures and the location of D-loop strand termination, additional mechanisms of length mutation may be needed to explain the range of mtDNA length variants maintained in these populations. The balance between genetic drift and mutation in maintaining this length polymorphism is estimated through a hierarchical analysis of diversity of mtDNA length variation in the Iceland samples. Eighty percent of the diversity lies within individuals, 8% among individuals and 12% among localities. An estimate of theta = 2N(eo) mu greater than 1 indicates that this system is characterized by a high mutation rate and is governed primarily by deterministic dynamics. The sequences of repeat arrays from fish collected in Norway, Iceland and George's Bank show no nucleotide variation suggesting that there is very little substructuring to the North Atlantic cod population.

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