The contribution of mitochondrial thymidylate synthesis in preventing the nuclear genome stress

Abstract Comparison of the levels of nucleotide diversity in humans and apes may provide much insight into the mechanisms of maintenance of DNA polymorphism and the demographic history of these organisms. In the past, abundant mitochondrial DNA (mtDNA) polymorphism data indicated that nucleotide diversity (π) is more than threefold higher in chimpanzees than in humans. Furthermore, it has recently been claimed, on the basis of limited data, that this is also true for nuclear DNA. In this study we sequenced 50 noncoding, nonrepetitive DNA segments randomly chosen from the nuclear genome in 9 bonobos and 17 chimpanzees. Surprisingly, the π value for bonobos is only 0.078%, even somewhat lower than that (0.088%) for humans for the same 50 segments. The π values are 0.092, 0.130, and 0.082% for East, Central, and West African chimpanzees, respectively, and 0.132% for all chimpanzees. These values are similar to or at most only 1.5 times higher than that for humans. The much larger difference in mtDNA diversity than in nuclear DNA diversity between humans and chimpanzees is puzzling. We speculate that it is due mainly to a reduction in effective population size (Ne) in the human lineage after the human-chimpanzee divergence, because a reduction in Ne has a stronger effect on mtDNA diversity than on nuclear DNA diversity.

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Development of a mito-CRISPR system for generating mitochondrial DNA-deleted strain in Saccharomyces cerevisiae

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbaa119 ◽

2020 ◽

Vol 85 (4) ◽

pp. 895-901

Author(s):

Takamitsu Amai ◽

Tomoka Tsuji ◽

Mitsuyoshi Ueda ◽

Kouichi Kuroda

Keyword(s):

Saccharomyces Cerevisiae ◽

Mitochondrial Dna ◽

Ethidium Bromide ◽

Nuclear Genome ◽

Target Sequence ◽

Guide Rna ◽

Crispr System ◽

Mitochondrial Target ◽

Gene Treatment ◽

Mtdna Deletion

ABSTRACT Mitochondrial dysfunction can occur in a variety of ways, most often due to the deletion or mutation of mitochondrial DNA (mtDNA). The easy generation of yeasts with mtDNA deletion is attractive for analyzing the functions of the mtDNA gene. Treatment of yeasts with ethidium bromide is a well-known method for generating ρ° cells with complete deletion of mtDNA from Saccharomyces cerevisiae. However, the mutagenic effects of ethidium bromide on the nuclear genome cannot be excluded. In this study, we developed a “mito-CRISPR system” that specifically generates ρ° cells of yeasts. This system enabled the specific cleavage of mtDNA by introducing Cas9 fused with the mitochondrial target sequence at the N-terminus and guide RNA into mitochondria, resulting in the specific generation of ρ° cells in yeasts. The mito-CRISPR system provides a concise technology for deleting mtDNA in yeasts.

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Chromosomal assembly of the nuclear genome of the endosymbiont-bearing trypanosomatid Angomonas deanei

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkaa018 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

John W Davey ◽

Carolina M C Catta-Preta ◽

Sally James ◽

Sarah Forrester ◽

Maria Cristina M Motta ◽

...

Keyword(s):

Chromosome Number ◽

Noncoding Rnas ◽

Nuclear Genome ◽

Supernumerary Chromosome ◽

Ribosomal Rnas ◽

Protein Coding ◽

Transfer Rnas ◽

Protein Coding Genes ◽

Oxford Nanopore ◽

Genome Assemblies

Abstract Angomonas deanei is an endosymbiont-bearing trypanosomatid with several highly fragmented genome assemblies and unknown chromosome number. We present an assembly of the A. deanei nuclear genome based on Oxford Nanopore sequence that resolves into 29 complete or close-to-complete chromosomes. The assembly has several previously unknown special features; it has a supernumerary chromosome, a chromosome with a 340-kb inversion, and there is a translocation between two chromosomes. We also present an updated annotation of the chromosomal genome with 10,365 protein-coding genes, 59 transfer RNAs, 26 ribosomal RNAs, and 62 noncoding RNAs.

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Identification and characterisation of mitochondrial sequences integrated into the ovine nuclear genome

Animal Genetics ◽

10.1111/age.13096 ◽

2021 ◽

Author(s):

M. Féménia ◽

M. Charles ◽

A. Boulling ◽

D. Rocha

Keyword(s):

Nuclear Genome ◽

Mitochondrial Sequences

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Mitochondrien unter Stress: Die Rolle der Präsequenzprotease MPP

BIOspektrum ◽

10.1007/s12268-021-1589-1 ◽

2021 ◽

Vol 27 (4) ◽

pp. 390-393

Author(s):

F.-Nora Vögtle

Keyword(s):

Stress Response ◽

Cellular Stress ◽

Critical Role ◽

Mitochondrial Protein ◽

Nuclear Genome ◽

Cellular Stress Response ◽

Mitochondrial Proteins ◽

Protein Biogenesis ◽

Cellular Integrity

AbstractThe majority of mitochondrial proteins are encoded in the nuclear genome, so that the nearly entire proteome is assembled by post-translational preprotein import from the cytosol. Proteomic imbalances are sensed and induce cellular stress response pathways to restore proteostasis. Here, the mitochondrial presequence protease MPP serves as example to illustrate the critical role of mitochondrial protein biogenesis and proteostasis on cellular integrity.

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copia-, gypsy- and LINE-Like Retrotransposon Fragments in the Mitochondrial Genome of Arabidopsis thaliana

Genetics ◽

10.1093/genetics/142.2.579 ◽

1996 ◽

Vol 142 (2) ◽

pp. 579-585 ◽

Cited By ~ 3

Author(s):

Volker Knoop ◽

Michael Unseld ◽

Joachim Marienfeld ◽

Petra Brandt ◽

Sabine Sünkel ◽

...

Keyword(s):

Arabidopsis Thaliana ◽

Mitochondrial Genome ◽

Evolutionary History ◽

Nuclear Genome ◽

Plant Mitochondrial Genome ◽

Gypsy Group ◽

History Of

Abstract Several retrotransposon fragments are integrated in the mitochondrial genome of Arabidopsis thaliana. These insertions are derived from all three classes of nuclear retrotransposons, the Tyl/copia, Ty3/gypsy- and non-LTR/LINE-families. Members of the Ty3/gypsy group of elements have not yet been identified in the nuclear genome of Arabidopsis. The varying degrees of similarity with nuclear elements and the dispersed locations of the sequences in the mitochondrial genome suggest numerous independent transfer-insertion events in the evolutionary history of this plant mitochondrial genome. Overall, we estimate remnants of retrotransposons to cover ≥5% of the mitochondrial genome in Arabidopsis.

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Risk of cardiac manifestations in adult mitochondrial disease caused by nuclear genetic defects

Open Heart ◽

10.1136/openhrt-2020-001510 ◽

2021 ◽

Vol 8 (1) ◽

pp. e001510

Author(s):

Albert Zishen Lim ◽

Daniel M Jones ◽

Matthew G D Bates ◽

Andrew M Schaefer ◽

John O'Sullivan ◽

...

Keyword(s):

Mitochondrial Disease ◽

Nuclear Dna ◽

Laboratory Data ◽

Nuclear Genome ◽

Nuclear Gene ◽

Left Ventricular ◽

Adult Patients ◽

Limited Information ◽

Cardiac Abnormalities ◽

Cardiac Manifestations

ObjectiveRegular cardiac surveillance is advocated for patients with primary mitochondrial DNA disease. However, there is limited information to guide clinical practice in mitochondrial conditions caused by nuclear DNA defects. We sought to determine the frequency and spectrum of cardiac abnormalities identified in adult mitochondrial disease originated from the nuclear genome.MethodsAdult patients with a genetically confirmed mitochondrial disease were identified and followed up at the national clinical service for mitochondrial disease in Newcastle upon Tyne, UK (January 2009 to December 2018). Case notes, molecular genetics reports, laboratory data and cardiac investigations, including serial electrocardiograms and echocardiograms, were reviewed.ResultsIn this cohort-based observational study, we included 146 adult patients (92 women) (mean age 53.6±18.7 years, 95% CI 50.6 to 56.7) with a mean follow-up duration of 7.9±5.1 years (95% CI 7.0 to 8.8). Eleven different nuclear genotypes were identified: TWNK, POLG, RRM2B, OPA1, GFER, YARS2, TYMP, ETFDH, SDHA, TRIT1 and AGK. Cardiac abnormalities were detected in 14 patients (9.6%). Seven of these patients (4.8%) had early-onset cardiac manifestations: hypertrophic cardiomyopathy required cardiac transplantation (AGK; n=2/2), left ventricular (LV) hypertrophy and bifascicular heart block (GFER; n=2/3) and mild LV dysfunction (GFER; n=1/3, YARS2; n=1/2, TWNK; n=1/41). The remaining seven patients had acquired heart disease most likely related to conventional cardiovascular risk factors and presented later in life (14.6±12.8 vs 55.1±8.9 years, p<0.0001).ConclusionsOur findings demonstrate that the risk of cardiac involvement is genotype specific, suggesting that routine cardiac screening is not indicated for most adult patients with nuclear gene-related mitochondrial disease.

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Nuclear genome-wide associations with mitochondrial heteroplasmy

Science Advances ◽

10.1126/sciadv.abe7520 ◽

2021 ◽

Vol 7 (12) ◽

pp. eabe7520

Author(s):

Priyanka Nandakumar ◽

Chao Tian ◽

Jared O’Connell ◽

David Hinds ◽

Andrew D. Paterson ◽

...

Keyword(s):

Nuclear Genome ◽

Multiple Roles ◽

European Ancestry ◽

Mitochondrial Transcription Factor ◽

Genome Wide ◽

Mtdna Sequence ◽

Nuclear Component ◽

Mitochondrial Transcription Factor A ◽

Mitochondrial Heteroplasmy ◽

The Stability

The role of the nuclear genome in maintaining the stability of the mitochondrial genome (mtDNA) is incompletely known. mtDNA sequence variants can exist in a state of heteroplasmy, which denotes the coexistence of organellar genomes with different sequences. Heteroplasmic variants that impair mitochondrial capacity cause disease, and the state of heteroplasmy itself is deleterious. However, mitochondrial heteroplasmy may provide an intermediate state in the emergence of novel mitochondrial haplogroups. We used genome-wide genotyping data from 982,072 European ancestry individuals to evaluate variation in mitochondrial heteroplasmy and to identify the regions of the nuclear genome that affect it. Age, sex, and mitochondrial haplogroup were associated with the extent of heteroplasmy. GWAS identified 20 loci for heteroplasmy that exceeded genome-wide significance. This included a region overlapping mitochondrial transcription factor A (TFAM), which has multiple roles in mtDNA packaging, replication, and transcription. These results show that mitochondrial heteroplasmy has a heritable nuclear component.

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