Konstantin Popadin

Konstantin Popadin
University of Lausanne | UNIL · Center for Integrative Genomics (CIG)

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32
Publications
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236
Citations

Publications

Publications (32)
Article
Full-text available
People living with human immunodeficiency virus (PLWH) have significantly increased risk for cardiovascular disease in part due to inflammation and immune dysregulation. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition and expansion of hematopoietic stem cells due to leukemogenic driver mutations, increases risk f...
Article
Full-text available
The hypothesis that the evolution of humans involves hybridization between diverged species has been actively debated in recent years. We present the following novel evidence in support of this hypothesis: the analysis of nuclear pseudogenes of mtDNA (“NUMTs”). NUMTs are considered “mtDNA fossils” as they preserve sequences of ancient mtDNA and thu...
Preprint
Full-text available
The mutational spectrum of the mitochondrial DNA (mtDNA) does not resemble any of the known mutational signatures of the nuclear genome and variation in mtDNA mutational spectra between different tissues and organisms is still incomprehensible. Since mitochondria is tightly involved in aerobic energy production, it is expected that mtDNA mutational...
Preprint
Full-text available
The resilience of the mitochondrial genome to a high mutational pressure depends, in part, on purifying selection against detrimental mutations in the germline. It is crucial to understand the mechanisms of this process. Recently, Floros et al. concluded that much of the purifying selection takes place during the proliferation of primordial germ ce...
Preprint
Full-text available
The A-to-G point mutation at position 3243 in the human mitochondrial genome (m.3243A>G) is the most common pathogenic mtDNA variant responsible for disease in humans. It is widely accepted that m.3243A>G levels decrease in blood with age, and correction representing ~2% annual decline is often applied to account for this change in mutation level....
Preprint
Full-text available
People living with human immunodeficiency virus (PLWH) have significantly increased risk for cardiovascular disease in part due to inflammation and immune dysregulation. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition and expansion of hematopoietic stem cells due to leukemogenic driver mutations, increases risk f...
Preprint
Full-text available
Mitochondrial mutational signature is very conserved and low deviations between species have been associated with longevity. By reconstructing species-specific mtDNA mutational spectrum for ray-finned fishes (Actinopterygii), we observed that temperature is a strong additional factor shaping the mtDNA mutational spectrum in ectotherms. The analysis...
Preprint
Full-text available
Ageing 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...
Article
Full-text available
A wealth of specialized neuroendocrine command systems intercalated within the hypothalamus control the most fundamental physiological needs in vertebrates1,2. Nevertheless, we lack a developmental blueprint that integrates the molecular determinants of neuronal and glial diversity along temporal and spatial scales of hypothalamus development3. Her...
Preprint
Full-text available
It has been shown recently that mitochondrial (mtDNA) somatic variants are numerous enough to trace cellular lineages in our body. Here we extend this statement and demonstrate that mtDNA variants can be interpreted not only as neutral markers of cell divisions but the relative frequency of different mtDNA substitutions (i.e. mtDNA mutational spect...
Article
Full-text available
Mitochondrial DNA encodes core subunits of oxidative phosphorylation complex, and as a result of a complex regulatory crosstalk between nuclear and mitochondrial genomes the total number of mtDNA copies fits the requirements of each cell type. Deviations from the optimal number of mtDNA copies are expected to be deleterious and thus can cause some...
Article
Full-text available
Copy-number changes in 16p11.2 contribute significantly to neuropsychiatric traits. Besides the 600 kb BP4-BP5 CNV found in 0.5%–1% of individuals with autism spectrum disorders and schizophrenia and whose rearrangement causes reciprocal defects in head size and body weight, a second distal 220 kb BP2-BP3 CNV is likewise a potent driver of neuropsy...
Article
Full-text available
Copy-number changes in 16p11.2 contribute significantly to neuropsychiatric traits. Besides the 600 kb BP4-BP5 CNV found in 0.5%-1% of individuals with autism spectrum disorders and schizophrenia and whose rearrangement causes reciprocal defects in head size and body weight, a second distal 220 kb BP2-BP3 CNV is likewise a potent driver of neuropsy...
Poster
Full-text available
Numerous works describe correlations between mitochondrial DNA (mtDNA) properties and species-specific life-history traits: GC content increases with species longevity and decreases with basal metabolic rate; abundance of direct, inverted and complementary repeats decreases with maximal lifespan; mtDNA length decreases with mammalian body mass but...
Preprint
Full-text available
The question: human evolution- gradual process or a rapid discontinuous change? Whether human origin was a gradual process or a result of rapid change has been a focus of intense debate. Of particular interest is the climate change ~2.9-2.5 Ma, thought to have precipitated the separation of the genus Homo (~2.8Ma). The debate mostly concerned conti...
Preprint
Full-text available
The question: human evolution- gradual process or a rapid discontinuous change? Whether human origin was a gradual process or a result of rapid change has been a focus of intense debate. Of particular interest is the climate change ~2.9-2.5 Ma, thought to have precipitated the separation of the genus Homo (~2.8Ma). The debate mostly concerned conti...
Preprint
Full-text available
Introduction : Increasingly, the emergence and evolution of our species is being tied to genetic exchange between divergent lineages within ~1Ma (e.g., Neanderthals, Denisovans). However, little is known about genetic exchange during earlier (pre-1Ma) human evolution and between more divergent lineages. Results : We present evidence of hybridizatio...
Preprint
Full-text available
Introduction : Increasingly, the emergence and evolution of our species is being tied to genetic exchange between divergent lineages within ~1Ma (e.g., Neanderthals, Denisovans). However, little is known about genetic exchange during earlier (pre-1Ma) human evolution and between more divergent lineages. Results : We present evidence of hybridizatio...
Preprint
Full-text available
The question: human evolution- gradual process or a rapid discontinuous change? Whether human origin was a gradual process or a result of rapid change has been a focus of intense debate. Of particular interest is the climate change ~2.9-2.5 Ma, thought to have precipitated the separation of the genus Homo (~2.8Ma). The debate mostly concerned conti...
Article
Full-text available
The data and methods presented in this article are supplementing the research article "Integration of mtDNA pseudogenes into the nuclear genome coincides with speciation of the human genus. A hypothesis", DOI: 10.1016/j.mito.2016.12.001 [1]. Mitochondrial DNA is known to get inserted into nuclear DNA to form NUMTs, i.e. nuclear DNA pseudogenes of t...
Article
Full-text available
Fragments of mitochondrial DNA are known to get inserted into nuclear DNA to form NUMTs, i.e. nuclear pseudogenes of the mtDNA. The insertion of a NUMT is a rare event. Hundreds of pseudogenes have been cataloged in the human genome. NUMTs are, in essence, a special type of mutation with their own internal timer, which is synchronized with an estab...
Article
Full-text available
The mtDNA mutator mouse lacks the proofreading capacity of the sole mtDNA polymerase, leading to accumulation of somatic mtDNA mutations, and a profound premature aging phenotype including elevated oxidative stress and apoptosis, and reduced mitochondrial function. We have previously reported that endurance exercise alleviates the aging phenotype i...
Article
This commentary highlights the article by Müller-Höcker et al, which provides a different view on the distribution and role of mtDNA mutations in oncocytic tumors.
Data
Fig. S1 Predicted change in the number of different deletion types discovered in a sample as a function of the number of deletion molecules analyzed, depending on the shape of the assumed frequency distribution of deletions. Fig. S2 Fraction of deletion types represented by two or more molecules is a rough measure of ‘saturation’ of the coverage of...
Data
Table S1 Estimations of absolute sizes of clonal expansions.
Article
Full-text available
Somatic mtDNA mutations and deletions in particular are known to clonally expand within cells, eventually reaching detrimental intracellular concentrations. The possibility that clonal expansion is a slow process taking a lifetime had prompted an idea that founder mutations of mutant clones that cause mitochondrial dysfunction in the aged tissue mi...
Article
Full-text available
Perfect direct repeats and, in particular, the prominent 13 bp repeat, are thought to cause mitochondrial DNA (mtDNA) deletions, which have been associated with the aging process. Accordingly, individuals lacking the 13 bp repeat are highly prevalent among centenarians and overall number of perfect repeats in mammalian mitochondrial genomes negativ...

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