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Article
| Open Access
APOGEE 2: multi-layer machine-learning model for the interpretable prediction of mitochondrial missense variants
APOGEE 2 is a machine-learning tool for assessing the fragility of the mitochondrial genome, evaluating genetic variant pathogenicity and ultimately enhancing our understanding of the clinical heterogeneity of mitochondrial genetic diseases.
- Salvatore Daniele Bianco
- , Luca Parca
- & Tommaso Mazza
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Article
| Open Access
Origin of minicircular mitochondrial genomes in red algae
While the organelle genome is commonly considered to be a single circular DNA molecule, extensive variation exists. Here, the authors report multipartite minicircular genomes in red algae and indicate an origin driven by recombination due to loss of DNA replication, recombination, and repair genes.
- Yongsung Lee
- , Chung Hyun Cho
- & Hwan Su Yoon
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Article
| Open Access
A method for multiplexed full-length single-molecule sequencing of the human mitochondrial genome
Accurate analysis of mitochondrial DNA is important for mitochondrial disease clinical research and diagnostics. Here, authors present a method using Cas9 cleavage, nanopore sequencing and a custom pipeline to identify pathogenic variants, deletions and accurately quantify heteroplasmy to below 1%.
- Ieva Keraite
- , Philipp Becker
- & Ivo Glynne Gut
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Article
| Open Access
Association of mitochondrial DNA content, heteroplasmies and inter-generational transmission with autism
Most genetic studies of autism spectrum disorder (ASD) have focused on the nuclear genome. Here, the authors show that variations in mitochondrial DNA, detectable at birth, are also associated with risk of ASD.
- Yiqin Wang
- , Xiaoxian Guo
- & Zhenglong Gu
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Article
| Open Access
In vivo mitochondrial base editing via adeno-associated viral delivery to mouse post-mitotic tissue
Mutations in mitochondrial DNA can lead to clinically heterogeneous disease. Here the authors demonstrate in vivo base editing of mouse mitochondrial DNA in a post-mitotic tissue by AAV delivery of DddA-derived cytosine base editor (DdCBE).
- Pedro Silva-Pinheiro
- , Pavel A. Nash
- & Michal Minczuk
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Article
| Open Access
Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans
Recent evidence has questioned the dogma of strict maternal transmission of mitochondrial DNA (mtDNA) in humans. Wei et al. saw no evidence of paternal transmission of mtDNA in 11,035 human trios, and show that nuclear-mitochondrial segments (NUMTs) can give the impression of paternal mtDNA transmission, but are actually inherited through the nuclear genome.
- Wei Wei
- , Alistair T. Pagnamenta
- & Patrick F. Chinnery
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Article
| Open Access
Large-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and variance increase through lifetimes and generations
Mitochondrial populations in cells may consist of heteroplasmic mixtures of mtDNA types, and their evolution through development, aging and generations is central to genetic diseases. Here the authors dissect these population dynamics using a large mouse-based data set to characterise the dynamics of heteroplasmy mean and variance throughout life and across generations.
- Joerg P. Burgstaller
- , Thomas Kolbe
- & Iain G. Johnston
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Article
| Open Access
Identification of the remains of King Richard III
King Richard III was a controversial English King whose remains are presumably deposited in Grey Friars in Leicester. Here the authors sequence the mitochondrial genome and Y-chromosome DNA of the skeletal remains and living relatives of Richard III and confirm that the remains belong to King Richard III.
- Turi E. King
- , Gloria Gonzalez Fortes
- & Kevin Schürer
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Article
| Open Access
A barcode of organellar genome polymorphisms identifies the geographic origin of Plasmodium falciparum strains
Tracing the source of malarial infections is an important step towards monitoring and controlling the disease. Here, Preston et al. analyse sequence data from 711 isolates and design a genetic barcode based on combined mitochondrial and apicoplast genomes that is able to distinguish between malaria parasites isolated from different geographical regions.
- Mark D. Preston
- , Susana Campino
- & Taane G. Clark
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Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation
The mitochondrial transcription factor TFAM is a multifunctional DNA-binding protein essential for transcriptional regulation and mitochondrial DNA organization. Here, Ngo et al.present two novel crystal structures that provide additional mechanistic insight into how TFAM performs its diverse functions.
- Huu B. Ngo
- , Geoffrey A. Lovely
- & David C. Chan
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Analysis of mitochondrial genome diversity identifies new and ancient maternal lineages in Cambodian aborigines
Population genetics studies provide valuable insight into human evolution and migration. Here, the authors have sequenced mitochondrial DNA (mtDNA) from 1,054 Cambodians across 14 populations, reporting eight ancient mtDNA lineages and providing evidence for human migration to Southeast Asia via India.
- Xiaoming Zhang
- , Xuebin Qi
- & Bing Su
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Article
| Open Access
Use of domesticated pigs by Mesolithic hunter-gatherers in northwestern Europe
It is still not clear when the introduction of animal domestication in northwestern Europe occurred. Here the authors provide evidence that Mesolithic hunter-gatherers in Northern Germany already possessed domestic pigs, and pigs were present in the region ~500 years earlier than previously thought.
- Ben Krause-Kyora
- , Cheryl Makarewicz
- & Almut Nebel
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Protein sliding and DNA denaturation are essential for DNA organization by human mitochondrial transcription factor A
The mitochondrial transcription factor A (TFAM) mediates both mitochondrial transcription and DNA compaction, but how it achieves these two functions is unknown. In this study, TFAM is shown to slide along DNA and cause local melting, suggesting a mechanism for how TFAM modulates both transcription and compaction.
- Géraldine Farge
- , Niels Laurens
- & Gijs J.L. Wuite
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Larger mitochondrial DNA than Y-chromosome differences between matrilocal and patrilocal groups from Sumatra
Matrilocal and patrilocal populations are predicted to have greater genetic diversity in mitochondrial DNA and the Y-chromosome, respectively. Here, no difference in the diversity of the Y-chromosome was found in two such groups, suggesting that local diversity was caused by male gene flow in expanding populations.
- Ellen Dröfn Gunnarsdóttir
- , Madhusudan R. Nandineni
- & Mark Stoneking
Developing mitochondrial base editors with diverse context compatibility and high fidelity via saturated spacer library