Comparative mitochondrial genomics reveals a possible role of a recent duplication of NADH dehydrogenase subunit 5 in gene regulation

RAD51 is a recombinase that plays a pivotal role in homologous recombination. Although the role of RAD51 in homologous recombination has been extensively studied, it is unclear whether RAD51 can be involved in gene regulation as a co-factor. In this study, we found evidence that RAD51 may contribute to the regulation of genes involved in the autophagy pathway with E-box proteins such as USF1, USF2, and/or MITF in GM12878, HepG2, K562, and MCF-7 cell lines. The canonical USF binding motif (CACGTG) was significantly identified at RAD51-bound cis-regulatory elements in all four cell lines. In addition, genome-wide USF1, USF2, and/or MITF-binding regions significantly coincided with the RAD51-associated cis-regulatory elements in the same cell line. Interestingly, the promoters of genes associated with the autophagy pathway, such as ATG3 and ATG5, were significantly occupied by RAD51 and regulated by RAD51 in HepG2 and MCF-7 cell lines. Taken together, these results unveiled a novel role of RAD51 and provided evidence that RAD51-associated cis-regulatory elements could possibly be involved in regulating autophagy-related genes with E-box binding proteins.

Download Full-text

Ndufs4 ablation decreases synaptophysin expression in hippocampus

Scientific Reports ◽

10.1038/s41598-021-90127-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Subrata Kumar Shil ◽

Yoshiteru Kagawa ◽

Banlanjo Abdulaziz Umaru ◽

Fumika Nanto-Hara ◽

Hirofumi Miyazaki ◽

...

Keyword(s):

Nadh Dehydrogenase ◽

Leigh Syndrome ◽

Mitochondrial Respiratory Chain ◽

Mitochondrial Activity ◽

Mitochondrial Complex ◽

Neuronal Function ◽

Mouse Hippocampus ◽

Extracellular Regulated Kinase ◽

Presynaptic Protein

AbstractAltered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.

Download Full-text

Departure from Neutrality at the Mitochondrial NADH Dehydrogenase Subunit 2 Gene in Humans, but Not in Chimpanzees

Genetics ◽

10.1093/genetics/148.1.409 ◽

1998 ◽

Vol 148 (1) ◽

pp. 409-421 ◽

Cited By ~ 2

Author(s):

Cheryl A Wise ◽

Michaela Sraml ◽

Simon Easteal

Keyword(s):

Nadh Dehydrogenase ◽

Statistical Tests ◽

Low Frequency ◽

Nadh Dehydrogenase Subunit ◽

Nadh Dehydrogenase Subunit 2 ◽

Tests Of Neutrality ◽

Slightly Deleterious Mutations ◽

Neutral Marker ◽

Transmembrane Regions ◽

Interspecific Comparisons

Abstract To test whether patterns of mitochondrial DNA (mtDNA) variation are consistent with a neutral model of molecular evolution, nucleotide sequences were determined for the 1041 bp of the NADH dehydrogenase subunit 2 (ND2) gene in 20 geographically diverse humans and 20 common chimpanzees. Contingency tests of neutrality were performed using four mutational categories for the ND2 molecule: synonymous and nonsynonymous mutations in the transmembrane regions, and synonymous and nonsynonymous mutations in the surface regions. The following three topological mutational categories were also used: intraspecific tips, intraspecific interiors, and interspecific fixed differences. The analyses reveal a significantly greater number of nonsynonymous polymorphisms within human transmembrane regions than expected based on interspecific comparisons, and they are inconsistent with a neutral equilibrium model. This pattern of excess nonsynonymous polymorphism is not seen within chimpanzees. Statistical tests of neutrality, such as Tajima's D test, and the D and F tests proposed by Fu and Li, indicate an excess of low frequency polymorphisms in the human data, but not in the chimpanzee data. This is consistent with recent directional selection, a population bottleneck or background selection of slightly deleterious mutations in human mtDNA samples. The analyses further support the idea that mitochondrial genome evolution is governed by selective forces that have the potential to affect its use as a “neutral” marker in evolutionary and population genetic studies.

Download Full-text

Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies

Scientific Reports ◽

10.1038/s41598-021-82714-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cristian Carmeli ◽

Zoltán Kutalik ◽

Pashupati P. Mishra ◽

Eleonora Porcu ◽

Cyrille Delpierre ◽

...

Keyword(s):

Dna Methylation ◽

Gene Regulation ◽

Cohort Studies ◽

Early Life ◽

Life Experiences ◽

Socioeconomic Disadvantage ◽

Mediating Role ◽

The Impact ◽

The Relationship

AbstractIndividuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.

Download Full-text

Molecular determination of the origin of acephalic cysticercus

Parasitology ◽

10.1017/s0031182004006262 ◽

2004 ◽

Vol 130 (2) ◽

pp. 239-246 ◽

Cited By ~ 8

Author(s):

J.-Y. CHUNG ◽

W.-G. KHO ◽

S.-Y. HWANG ◽

E.-Y. JE ◽

Y.-T. CHUNG ◽

...

Keyword(s):

Nadh Dehydrogenase ◽

Fatal Outcome ◽

Constitutive Expression ◽

Molecular Data ◽

Molecular Characteristics ◽

Nadh Dehydrogenase Subunit ◽

Subarachnoidal Space ◽

Species Specific ◽

Molecular Determination

Acephalic cysticercus (Ac), a rarely developed multilobulated and nonencysted form of larval Taenia, causes hydrocephalus or adhesive arachnoiditis in the ventricles and subarachnoidal space that often lead to fatal outcome in affected patients. Ac has been proposed to originate from T. solium on the basis of morphological features, while no molecular data supporting the presumption have been available. In the present study, we investigated the immunological properties as well as molecular characteristics of Ac that was obtained surgically from 6 patients. Immunoblotting of the cyst fluid from Ac samples demonstrated the constitutive expression of a T. solium metacestode (TsM) 10 kDa protein. Specific antibodies against the truncated 10 kDa protein, which appears to be species specific for TsM cysticercosis, were detected in both serum and cerebrospinal fluid samples of Ac patients. Nucleotide sequences of mitochondrial cytochrome c oxidase subunit I (COI) and NADH dehydrogenase subunit 1 (ND1) genes of Ac were almost identical to those of T. solium but differed substantially from those of the other Taenia species. In phylogenetic analysis, Ac clustered with T. solium in a well-supported clade. Our results strongly suggest that Ac may have originated from T. solium.

Download Full-text