NUMTs Can Imitate Biparental Transmission of mtDNA—A Case in Drosophila melanogaster

Parakatselaki, Maria-Eleni; Zhu, Chen-Tseh; Rand, David M.; Ladoukakis, Emmanuel D.

doi:10.3390/genes13061023

Cited by 4 publications

(4 citation statements)

References 46 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NUMTs have a major impact on mitogenomes and they may confound cases of heteroplasmy (Parakatselaki & Ladoukakis, 2021; Parakatselaki et al, 2022). We used the latest version of NOVOPlasty that performed additional re-alignments, phasing and thresholds (in length and mutations) to distinguish between NUMTs and heteroplasmy.…”

Section: Discussionmentioning

confidence: 99%

“…Heteroplasmy can result from either mutational mechanisms or a paternal leak of mtDNA (Ingman & Gyllensten, 2006;Ye et al, 2022). With older techniques, the accurate detection of heteroplasmy was difficult to achieve because NUMTs mimic polymorphism (Parakatselaki et al, 2022). However, considerable levels of heteroplasmy have been reported in nematodes (C. elegans, by Konrad et al, 2017), crabs (Koolkarnkhai et al, 2019;Rodríguez-Pena et al, 2020), birds such as the partridge (Gandolfi et al, 2017;Pizzirani et al, 2020) and the Crested ibis (He et al, 2013), mammals (Burgstaller et al, 2018), turtles (Tikochinski et al, 2020) and the Tuatara (Macey et al, 2021).…”

Section: Detecting Heteroplasmy From Hts Data and Numtsmentioning

confidence: 99%

“…An additional advantage of using HTS for mitogenome assembly, is that the process captures the total mtDNA from whole-genome sequencing and overcomes the hurdles of older methods, such as long-range PCR. Older methods can produce inaccuracies due to the amplification of nuclear mitochondrial DNA segments (NUMTs), the variation of sequences at primer bonding sites and changes in gene structure (Mueller & Boore, 2005; Cameron, 2014; Parakatselaki et al, 2022). On the other hand, mitogenomes still present challenges that only LRS can overcome, such as accurately capturing gene arrangements, long TRs and long duplications (Konrad et al, 2017; Torres et al, 2019; Zardoya, 2020; Montaña-Lozano et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Heteroplasmy and tandem repeats reveal adaptation to elevation in the New World Jays (Aves: Corvidae)

Termignoni-Garcia,

Bougiouri,

Edwards

2023

Preprint

View full text Add to dashboard Cite

Advances in high-throughput sequencing (HTS) and bioinformatic tools have enabled the quick and cost-efficient assembly of complete mitochondrial genomes (mitogenomes) in non-model organisms. Consequently, new evidence of heteroplasmy, recombination and paternal leakage in mitogenomes has increased. In this study, we utilized HTS data from whole-genome sequencing to assemble the first complete mitogenomes of nine species of New World Jays (NWJs), covering all genera. We further investigated the evolution of heteroplasmy, tandem repeats (TRs) and signatures of natural selection. Our results showed a molecular shift in the adaptation to low elevation in the NWJs. Among the species studied, we found 10 heteroplasmic sites either containing TRs in the same site or 1 to 300 nucleotides adjacent; one species-specific TR in a transfer RNA (tRNA-P) potentially associated with low elevation; one phylogenetic branch with evidence of episodic positive selection also associated with low elevation; and 5 codon sites with strong support for positive selection. We referred to the heteroplasmy-TR interaction and its possible role with regulation, recombination and paternal leakage in the mitogenomes. Finally, phylogenetic relationships were in agreement with previous studies and we discussed how selective pressure on genes from the oxidative phosphorylation pathway (OXPHOS) may benefit species from low-elevation habitats. Although these findings in the NWJs require further investigation, this study offers promising insights about the evolution of mitogenomes in birds.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Detecting Heteroplasmy From Hts Data and Numtsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Heteroplasmy and tandem repeats reveal adaptation to elevation in the New World Jays (Aves: Corvidae)

Termignoni-Garcia,

Bougiouri,

Edwards

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Nuclear-mitochondrial DNA segments (NUMTs) are fragments of the mitochondrial genome (mtDNA) that have been inserted into the nuclear genome of multiple organisms, including domestic cats, great apes, fruit flies, and humans [1][2][3][4][5]. NUMTs are likely due to multiple insertion events rather than duplications of nuclear DNA [6].…”

Section: Introductionmentioning

confidence: 99%

The Mighty NUMT: Mitochondrial DNA Flexing Its Code in the Nuclear Genome

et al. 2023

View full text Add to dashboard Cite

Nuclear-mitochondrial DNA segments (NUMTs) are mitochondrial DNA (mtDNA) fragments that have been inserted into the nuclear genome. Some NUMTs are common within the human population but most NUMTs are rare and specific to individuals. NUMTs range in size from 24 base pairs to encompassing nearly the entire mtDNA and are found throughout the nuclear genome. Emerging evidence suggests that the formation of NUMTs is an ongoing process in humans. NUMTs contaminate sequencing results of the mtDNA by introducing false positive variants, particularly heteroplasmic variants present at a low variant allele frequency (VAF). In our review, we discuss the prevalence of NUMTs in the human population, the potential mechanisms of de novo NUMT insertion via DNA repair mechanisms, and provide an overview of the existing approaches for minimizing NUMT contamination. Apart from filtering known NUMTs, both wet lab-based and computational methods can be used to minimize the contamination of NUMTs in analyses of human mtDNA. Current approaches include: (1) isolating mitochondria to enrich for mtDNA; (2) applying basic local alignment to identify NUMTs for subsequent filtering; (3) bioinformatic pipelines for NUMT detection; (4) k-mer-based NUMT detection; and (5) filtering candidate false positive variants by mtDNA copy number, VAF, or sequence quality score. Multiple approaches must be applied in order to effectively identify NUMTs in samples. Although next-generation sequencing is revolutionizing our understanding of heteroplasmic mtDNA, it also raises new challenges with the high prevalence and individual-specific NUMTs that need to be handled with care in studies of mitochondrial genetics.

show abstract

Mitochondrial genome plasticity of mammalian species

Biró,

Gál,

Fekete

et al. 2024

BMC Genomics

View full text Add to dashboard Cite

There is an ongoing process in which mitochondrial sequences are being integrated into the nuclear genome. The importance of these sequences has already been revealed in cancer biology, forensic, phylogenetic studies and in the evolution of the eukaryotic genetic information. Human and numerous model organisms’ genomes were described from those sequences point of view. Furthermore, recent studies were published on the patterns of these nuclear localised mitochondrial sequences in different taxa.However, the results of the previously released studies are difficult to compare due to the lack of standardised methods and/or using few numbers of genomes. Therefore, in this paper our primary goal is to establish a uniform mining pipeline to explore these nuclear localised mitochondrial sequences.Our results show that the frequency of several repetitive elements is higher in the flanking regions of these sequences than expected. A machine learning model reveals that the flanking regions’ repetitive elements and different structural characteristics are highly influential during the integration process.In this paper, we introduce a general mining pipeline for all mammalian genomes. The workflow is publicly available and is believed to serve as a validated baseline for future research in this field. We confirm the widespread opinion, on - as to our current knowledge - the largest dataset, that structural circumstances and events corresponding to repetitive elements are highly significant. An accurate model has also been trained to predict these sequences and their corresponding flanking regions.

show abstract

NUMTs Can Imitate Biparental Transmission of mtDNA—A Case in Drosophila melanogaster

Cited by 4 publications

References 46 publications

Heteroplasmy and tandem repeats reveal adaptation to elevation in the New World Jays (Aves: Corvidae)

Heteroplasmy and tandem repeats reveal adaptation to elevation in the New World Jays (Aves: Corvidae)

The Mighty NUMT: Mitochondrial DNA Flexing Its Code in the Nuclear Genome

Mitochondrial genome plasticity of mammalian species

Contact Info

Product

Resources

About