Diatom centromeres suggest a mechanism for nuclear DNA acquisition

Centromeres are essential for cell division and growth in all eukaryotes, and knowledge of their sequence and structure guides the development of artificial chromosomes for functional cellular biology studies. Centromeric proteins are conserved among eukaryotes; however, centromeric DNA sequences are highly variable. We combined forward and reverse genetic approaches with chromatin immunoprecipitation to identify centromeres of the model diatom Phaeodactylum tricornutum. We observed 25 unique centromere sequences typically occurring once per chromosome, a finding that helps to resolve nuclear genome organization and indicates monocentric regional centromeres. Diatom centromere sequences contain low-GC content regions but lack repeats or other conserved sequence features. Native and foreign sequences with similar GC content to P. tricornutum centromeres can maintain episomes and recruit the diatom centromeric histone protein CENH3, suggesting nonnative sequences can also function as diatom centromeres. Thus, simple sequence requirements may enable DNA from foreign sources to persist in the nucleus as extrachromosomal episomes, revealing a potential mechanism for organellar and foreign DNA acquisition.

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Diatom Centromeres Suggest a Novel Mechanism for Nuclear Gene Acquisition

10.1101/096016 ◽

2016 ◽

Author(s):

Rachel E. Diner ◽

Chari M. Noddings ◽

Nathan C. Lian ◽

Anthony K. Kang ◽

Jeffrey B. McQuaid ◽

...

Keyword(s):

Dna Sequences ◽

Gc Content ◽

Nuclear Genome ◽

Nuclear Gene ◽

Artificial Chromosomes ◽

Conserved Sequence ◽

Gene Acquisition ◽

Eukaryotic Dna ◽

Sequence Requirements ◽

Dna Acquisition

AbstractCentromeres are essential for cell division and growth in all eukaryotes, and knowledge of their sequence and structure guides the development of artificial chromosomes for functional cellular biology studies. Centromeric proteins are conserved among eukaryotes; however, centromeric DNA sequences are highly variable. We combined forward and reverse genetic approaches with chromatin immunoprecipitation to identify centromeres of the model diatom Phaeodactylum tricornutum. Diatom centromere sequences contain low GC content regions and an abundance of long contiguous AT windows, but lack repeats or other conserved sequence features. Native and foreign sequences of similar GC content can maintain episomes and recruit the diatom centromeric histone protein CENP-A, suggesting non-native sequences can also function as diatom centromeres. Thus, simple sequence requirements enable DNA from foreign sources to incorporate into the nuclear genome repertoire as stable extra-chromosomal episomes, revealing a potential mechanism for bacterial and foreign eukaryotic DNA acquisition.

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Demonstration of Apoptotic Cells in Tissue Sections by In Situ Hybridization Using Digoxigenin-labeled Poly(A) Oligonucleotide Probes to Detect Thymidine-rich DNA Sequences

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215549704500103 ◽

1997 ◽

Vol 45 (1) ◽

pp. 13-20 ◽

Cited By ~ 11

Author(s):

David A Hilton ◽

Seth Love ◽

Rachel Barber

Keyword(s):

In Situ Hybridization ◽

Dna Sequences ◽

Nuclear Dna ◽

Early Stage ◽

Nuclear Genome ◽

Apoptotic Cells ◽

Oligonucleotide Probes ◽

Tissue Sections ◽

Fresh Frozen

The recognition of apoptotic cells by morphological appearance alone may be difficult. We have investigated the use of in situ hybridization (ISH) with digoxigenin-labeled poly(A) probes to detect apoptotic cells in tissue sections. This method was compared to conventional morphologic assessment and in situ end-labeling (ISEL) in a range of tissues in which apoptosis is known to occur. ISH with poly(A) probes detected apoptotic nuclei in all tissues in which there was evidence of apoptosis as judged by conventional histology. ISH and, to a lesser extent, ISEL preferentially labeled shrunken but still intact nuclei with margination of chromatin, presumably at an early stage of apoptosis. The poly(A) hybridization was abolished by pretreatment of tissue sections with DNAse. After denaturation of DNA, poly(A) hybridized to nuclei in all cells. No convincing hybridization signal was detected in alcohol-fixed or fresh-frozen sections. Both ISEL and ISH labeled some of the nuclei in ischemic tissues. ISH with poly(A) oligonucleotide probes offers a simple alternative to ISEL for detection of cells in early stages of apoptosis. These probes hybridize to thymidine-rich sequences of DNA in the highly repeated Alu sequences within the nuclear genome. These sequences are believed to become available for hybridization after formalin fixation and paraffin embedding as a result of the apoptosis-related increase in the susceptibility of nuclear DNA to denaturation.

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Nuclear and mitochondrial DNA sequences from two Denisovan individuals

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1519905112 ◽

2015 ◽

Vol 112 (51) ◽

pp. 15696-15700 ◽

Cited By ~ 75

Author(s):

Susanna Sawyer ◽

Gabriel Renaud ◽

Bence Viola ◽

Jean-Jacques Hublin ◽

Marie-Theres Gansauge ◽

...

Keyword(s):

Dna Sequence ◽

Dna Sequences ◽

Nuclear Dna ◽

Sequence Data ◽

Nuclear Genome ◽

Extended Period ◽

Sister Group ◽

Morphological Description ◽

Dna Sequence Data ◽

Mtdna Sequence

Denisovans, a sister group of Neandertals, have been described on the basis of a nuclear genome sequence from a finger phalanx (Denisova 3) found in Denisova Cave in the Altai Mountains. The only other Denisovan specimen described to date is a molar (Denisova 4) found at the same site. This tooth carries a mtDNA sequence similar to that of Denisova 3. Here we present nuclear DNA sequences from Denisova 4 and a morphological description, as well as mitochondrial and nuclear DNA sequence data, from another molar (Denisova 8) found in Denisova Cave in 2010. This new molar is similar to Denisova 4 in being very large and lacking traits typical of Neandertals and modern humans. Nuclear DNA sequences from the two molars form a clade with Denisova 3. The mtDNA of Denisova 8 is more diverged and has accumulated fewer substitutions than the mtDNAs of the other two specimens, suggesting Denisovans were present in the region over an extended period. The nuclear DNA sequence diversity among the three Denisovans is comparable to that among six Neandertals, but lower than that among present-day humans.

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Faculty Opinions recommendation of Selective silencing of foreign DNA with low GC content by the H-NS protein in Salmonella.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1032929.388992 ◽

2006 ◽

Author(s):

Gene Nester

Keyword(s):

Gc Content ◽

Foreign Dna

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Low Nucleotide Diversity in Chimpanzees and Bonobos

Genetics ◽

10.1093/genetics/164.4.1511 ◽

2003 ◽

Vol 164 (4) ◽

pp. 1511-1518 ◽

Cited By ~ 1

Author(s):

Ning Yu ◽

Michael I Jensen-Seaman ◽

Leona Chemnick ◽

Judith R Kidd ◽

Amos S Deinard ◽

...

Keyword(s):

Nucleotide Diversity ◽

Nuclear Dna ◽

Demographic History ◽

Nuclear Genome ◽

Limited Data ◽

Effective Population ◽

East Central ◽

Dna Diversity ◽

History Of ◽

Mtdna Diversity

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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DNABERT: pre-trained Bidirectional Encoder Representations from Transformers model for DNA-language in genome

Bioinformatics ◽

10.1093/bioinformatics/btab083 ◽

2021 ◽

Author(s):

Yanrong Ji ◽

Zhihan Zhou ◽

Han Liu ◽

Ramana V Davuluri

Keyword(s):

Dna Sequences ◽

Regulatory Elements ◽

Ease Of Use ◽

Fine Tuning ◽

Supplementary Information ◽

Sequence Motifs ◽

Semantic Relationship ◽

Accurate Identification ◽

Conserved Sequence ◽

Genome Wide

Abstract Motivation Deciphering the language of non-coding DNA is one of the fundamental problems in genome research. Gene regulatory code is highly complex due to the existence of polysemy and distant semantic relationship, which previous informatics methods often fail to capture especially in data-scarce scenarios. Results To address this challenge, we developed a novel pre-trained bidirectional encoder representation, named DNABERT, to capture global and transferrable understanding of genomic DNA sequences based on up and downstream nucleotide contexts. We compared DNABERT to the most widely used programs for genome-wide regulatory elements prediction and demonstrate its ease of use, accuracy and efficiency. We show that the single pre-trained transformers model can simultaneously achieve state-of-the-art performance on prediction of promoters, splice sites and transcription factor binding sites, after easy fine-tuning using small task-specific labeled data. Further, DNABERT enables direct visualization of nucleotide-level importance and semantic relationship within input sequences for better interpretability and accurate identification of conserved sequence motifs and functional genetic variant candidates. Finally, we demonstrate that pre-trained DNABERT with human genome can even be readily applied to other organisms with exceptional performance. We anticipate that the pre-trained DNABERT model can be fined tuned to many other sequence analyses tasks. Availability and implementation The source code, pretrained and finetuned model for DNABERT are available at GitHub (https://github.com/jerryji1993/DNABERT). Supplementary information Supplementary data are available at Bioinformatics online.

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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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Mitochondrial DNA Methylation and Human Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22094594 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4594

Author(s):

Andrea Stoccoro ◽

Fabio Coppedè

Keyword(s):

Dna Methylation ◽

Mitochondrial Dna ◽

Mitochondrial Genome ◽

Nuclear Dna ◽

Epigenetic Modification ◽

Nuclear Genome ◽

Epigenetic Modifications ◽

Human Diseases ◽

Loop Region ◽

D Loop

Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases. Moreover, environmental factors, as well as nuclear DNA genetic variants, have been found to impair mtDNA methylation patterns. Some authors failed to find DNA methylation marks in the mitochondrial genome, suggesting that it is unlikely that this epigenetic modification plays any role in the control of the mitochondrial function. On the other hand, several other studies successfully identified the presence of mtDNA methylation, particularly in the mitochondrial displacement loop (D-loop) region, relating it to changes in both mtDNA gene transcription and mitochondrial replication. Overall, investigations performed until now suggest that methylation and hydroxymethylation marks are present in the mtDNA genome, albeit at lower levels compared to those detectable in nuclear DNA, potentially contributing to the mitochondria impairment underlying several human diseases.

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