scholarly journals Risk of mitochondrial deletions is affected by the global secondary structure of the mitochondrial genome

2019 ◽  
Author(s):  
Alina A. Mikhailova ◽  
Viktor Shamanskiy ◽  
Kristina Ushakova ◽  
Alina G. Mikhailova ◽  
Sergei Oreshkov ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Mitochondrial Genome ◽  
Contact Zone ◽  
Mitochondrial Encephalomyopathies ◽  
Deletion Formation ◽  
Potential Contact ◽  
Mtdna Replication ◽  
Mitochondrial Deletions ◽  
Nucleotide Repeats

AbstractAgeing is associated with accumulation of somatic mutations. This process is especially pronounced in mitochondrial genomes (mtDNA) of postmitotic cells, where the accumulation of somatic mitochondrial deletions is associated with healthy ageing and mitochondrial encephalomyopathies. Deletions are often flanked by direct nucleotide repeats, however, they do not provide an exhaustive explanation of deletion distribution. We hypothesized that in parallel with the role of direct repeats there is also a global secondary structure of mtDNA, shaping deletion formation. Analyzing the folding energies of the heavy chain, which stays single-stranded during mtDNA replication, we observed a potential contact zone between 6-9kb and 13-16kb of the major arc of mtDNA. Describing the distribution of deletions in the human mtDNA we demonstrated that the contact zone is 3-times more mutagenic under all else equal. The proposed topological model improves our understanding of the mechanisms of deletion formation in the human mitochondrial genome.

scholarly journals Landscape resistance constrains hybridization across contact zones in a reproductively and morphologically polymorphic salamander

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Guillermo Velo-Antón ◽  
André Lourenço ◽  
Pedro Galán ◽  
Alfredo Nicieza ◽  
Pedro Tarroso
Keyword(s):  
Contact Zone ◽  
Environmental Heterogeneity ◽  
Evolutionary Dynamics ◽  
Morphological Differentiation ◽  
Phenotypic Traits ◽  
Hybrid Zones ◽  
Landscape Resistance ◽  
Phenotypic Differentiation ◽  
Contact Zones

AbstractExplicitly accounting for phenotypic differentiation together with environmental heterogeneity is crucial to understand the evolutionary dynamics in hybrid zones. Species showing intra-specific variation in phenotypic traits that meet across environmentally heterogeneous regions constitute excellent natural settings to study the role of phenotypic differentiation and environmental factors in shaping the spatial extent and patterns of admixture in hybrid zones. We studied three environmentally distinct contact zones where morphologically and reproductively divergent subspecies of Salamandra salamandra co-occur: the pueriparous S. s. bernardezi that is mostly parapatric to its three larviparous subspecies neighbours. We used a landscape genetics framework to: (i) characterise the spatial location and extent of each contact zone; (ii) assess patterns of introgression and hybridization between subspecies pairs; and (iii) examine the role of environmental heterogeneity in the evolutionary dynamics of hybrid zones. We found high levels of introgression between parity modes, and between distinct phenotypes, thus demonstrating the evolution to pueriparity alone or morphological differentiation do not lead to reproductive isolation between these highly divergent S. salamandra morphotypes. However, we detected substantial variation in patterns of hybridization across contact zones, being lower in the contact zone located on a topographically complex area. We highlight the importance of accounting for spatial environmental heterogeneity when studying evolutionary dynamics of hybrid zones.

RNA secondary structure dependence in METTL3–METTL14 mRNA methylation is modulated by the N-terminal domain of METTL3

2020 ◽  
Vol 402 (1) ◽  
pp. 89-98
Author(s):  
Nathalie Meiser ◽  
Nicole Mench ◽  
Martin Hengesbach
Keyword(s):  
Secondary Structure ◽  
Rna Binding ◽  
Specific Protein ◽  
Structure Dependence ◽  
Terminal Domain ◽  
Methylation Assay ◽  
A Site ◽  
Methylation Activity

AbstractN6-methyladenosine (m6A) is the most abundant modification in mRNA. The core of the human N6-methyltransferase complex (MTC) is formed by a heterodimer consisting of METTL3 and METTL14, which specifically catalyzes m6A formation within an RRACH sequence context. Using recombinant proteins in a site-specific methylation assay that allows determination of quantitative methylation yields, our results show that this complex methylates its target RNAs not only sequence but also secondary structure dependent. Furthermore, we demonstrate the role of specific protein domains on both RNA binding and substrate turnover, focusing on postulated RNA binding elements. Our results show that one zinc finger motif within the complex is sufficient to bind RNA, however, both zinc fingers are required for methylation activity. We show that the N-terminal domain of METTL3 alters the secondary structure dependence of methylation yields. Our results demonstrate that a cooperative effect of all RNA-binding elements in the METTL3–METTL14 complex is required for efficient catalysis, and that binding of further proteins affecting the NTD of METTL3 may regulate substrate specificity.

Electronic Transport via Homopeptides: The Role of Side Chains and Secondary Structure

2015 ◽  
Vol 137 (30) ◽  
pp. 9617-9626 ◽  
Author(s):  
Lior Sepunaru ◽  
Sivan Refaely-Abramson ◽  
Robert Lovrinčić ◽  
Yulian Gavrilov ◽  
Piyush Agrawal ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Electronic Transport ◽  
Side Chains

scholarly journals Mitochondrial fission is required for proper nucleoid distribution within mitochondrial networks

2021 ◽  
Author(s):  
Hema Saranya Ilamathi ◽  
Mathieu Ouellet ◽  
Rasha Sabouny ◽  
Justine Desrochers-Goyette ◽  
Matthew A Lines ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Network Structure ◽  
Mitochondrial Fission ◽  
Healthy Population ◽  
Primary Cells ◽  
Mitochondrial Homeostasis ◽  
Mtdna Replication ◽  
Mitochondrial Networks ◽  
Regular Spacing

Mitochondrial DNA (mtDNA) maintenance is essential to sustain a functionally healthy population of mitochondria within cells. Proper mtDNA replication and distribution within mitochondrial networks are essential to maintain mitochondrial homeostasis. However, the fundamental basis of mtDNA segregation and distribution within mitochondrial networks is still unclear. To address these questions, we developed an algorithm, Mitomate tracker to unravel the global distribution of nucleoids within mitochondria. Using this tool, we decipher the semi-regular spacing of nucleoids across mitochondrial networks. Furthermore, we show that mitochondrial fission actively regulates mtDNA distribution by controlling the distribution of nucleoids within mitochondrial networks. Specifically, we found that primary cells bearing disease-associated mutations in the fission proteins DRP1 and MYH14 show altered nucleoid distribution, and acute enrichment of enlarged nucleoids near the nucleus. Further analysis suggests that the altered nucleoid distribution observed in the fission mutants is the result of both changes in network structure and nucleoid density. Thus, our study provides novel insights into the role of mitochondria fission in nucleoid distribution and the understanding of diseases caused by fission defects.

scholarly journals Emerging Role of the Guanine-Quadruplex DNA Secondary Structure in Epigenetics

2015 ◽  
pp. 271-284
Author(s):  
Aradhita Baral ◽  
Dhurjhoti Saha ◽  
Shantanu Chowdhury
Keyword(s):  
Secondary Structure ◽  
Dna Secondary Structure ◽  
Quadruplex Dna ◽  
Guanine Quadruplex

scholarly journals Comment on “Role of Mitochondrial Genome Mutations in Pathogenesis of Carotid Atherosclerosis”

2018 ◽  
Vol 2018 ◽  
pp. 1-2 ◽  
Author(s):  
Josef Finsterer ◽  
Sinda Zarrouk-Mahjoub
Keyword(s):  
Mitochondrial Genome ◽  
Carotid Atherosclerosis

Extensive hybridization between two Andean warbler species with shallow divergence in mtDNA

The Auk ◽  
2021 ◽  
Vol 138 (1) ◽  
Author(s):  
Laura N Céspedes-Arias ◽  
Andrés M Cuervo ◽  
Elisa Bonaccorso ◽  
Marialejandra Castro-Farias ◽  
Alejandro Mendoza-Santacruz ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Contact Zone ◽  
Hybrid Zone ◽  
Secondary Contact ◽  
Tropical Andes ◽  
Phenotypic Data ◽  
Geographic Ranges ◽  
Intermediate Phenotypes ◽  
Ecological Barriers

Abstract Studying processes acting on differentiated populations upon secondary contact, such as hybridization, is important to comprehensively understand how species are formed and maintained over time. However, avian speciation studies in the tropical Andes have largely focused on the role of topographic and ecological barriers promoting divergence in allopatry, seldom examining hybridization and introgression. We describe a hybrid zone involving 2 closely related Andean warblers (Parulidae), the Golden-fronted Redstart (Myioborus ornatus), and the Spectacled Redstart (Myioborus melanocephalus). Geographic ranges of these species abut near the Colombia-Ecuador border and many specimens from the region exhibit intermediate phenotypes, but a formal description of phenotypic variation in the contact zone was heretofore lacking. We collected specimens across a transect encompassing the area where ranges abut and areas where only “pure” parental phenotypes of M. ornatus chrysops and M. melanocephalus ruficoronatus occur. We described variation in plumage traits including patterns of head and ventral coloration and tail markings based on 321 specimens. To describe genetic variation in the contact zone and over a broader phylogeographic context, we used sequences of the mitochondrial ND2 gene for 219 individuals across the transect and the entire range of both species, including all subspecies, from Venezuela to Bolivia. We documented a hybrid zone ~200 km wide based on head coloration, where intermediate plumage phenotypes are most common and “pure” forms do not overlap geographically, consistent with extensive hybridization. Across the range of the M. ornatus–M. melanocephalus complex, mitochondrial genetic structure was shallow, with genetic breaks only coinciding clearly with one topographic feature. Such a low genetic structure is striking given the high diversity in plumage phenotypes and the current taxonomy of the group. Our phenotypic data suggest that barriers to hybridization are not strong, and allow us to postulate hypotheses to be tested using forthcoming genomic data.

scholarly journals Mechanisms of replication and repair in mitochondrial DNA deletion formation

2020 ◽  
Vol 48 (20) ◽  
pp. 11244-11258
Author(s):  
Gabriele A Fontana ◽  
Hailey L Gahlon
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Mitochondrial Dna Deletion ◽  
Deletion Formation ◽  
Dna Deletion ◽  
Mtdna Deletions ◽  
Mtdna Deletion

Abstract Deletions in mitochondrial DNA (mtDNA) are associated with diverse human pathologies including cancer, aging and mitochondrial disorders. Large-scale deletions span kilobases in length and the loss of these associated genes contributes to crippled oxidative phosphorylation and overall decline in mitochondrial fitness. There is not a united view for how mtDNA deletions are generated and the molecular mechanisms underlying this process are poorly understood. This review discusses the role of replication and repair in mtDNA deletion formation as well as nucleic acid motifs such as repeats, secondary structures, and DNA damage associated with deletion formation in the mitochondrial genome. We propose that while erroneous replication and repair can separately contribute to deletion formation, crosstalk between these pathways is also involved in generating deletions.

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