scholarly journals SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome

2020 ◽  
Author(s):  
Liguo Zhang ◽  
Alexsia Richards ◽  
Andrew Khalil ◽  
Emile Wogram ◽  
Haiting Ma ◽  
...  
Keyword(s):  
Human Genome ◽  
Dna Sequences ◽  
Cultured Cells ◽  
Rna Virus ◽  
Published Data ◽  
Data Sets ◽  
Chimeric Transcripts ◽  
Cell Genome ◽  
Viral Sequences ◽  
Hiv 1

Prolonged SARS-CoV-2 RNA shedding and recurrence of PCR-positive tests have been widely reported in patients after recovery, yet these patients most commonly are non-infectious. Here we investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome and that transcription of the integrated sequences might account for PCR-positive tests. In support of this hypothesis, we found chimeric transcripts consisting of viral fused to cellular sequences in published data sets of SARS-CoV-2 infected cultured cells and primary cells of patients, consistent with the transcription of viral sequences integrated into the genome. To experimentally corroborate the possibility of viral retro-integration, we describe evidence that SARS-CoV-2 RNAs can be reverse transcribed in human cells by reverse transcriptase (RT) from LINE-1 elements or by HIV-1 RT, and that these DNA sequences can be integrated into the cell genome and subsequently be transcribed. Human endogenous LINE-1 expression was induced upon SARS-CoV-2 infection or by cytokine exposure in cultured cells, suggesting a molecular mechanism for SARS-CoV-2 retro-integration in patients. This novel feature of SARS-CoV-2 infection may explain why patients can continue to produce viral RNA after recovery and suggests a new aspect of RNA virus replication.

scholarly journals Phylogenetic Estimation of Timescales Using Ancient DNA: The Effects of Temporal Sampling Scheme and Uncertainty in Sample Ages

2012 ◽  
Vol 30 (2) ◽  
pp. 253-262 ◽  
Author(s):  
Martyna Molak ◽  
Eline D. Lorenzen ◽  
Beth Shapiro ◽  
Simon Y.W. Ho
Keyword(s):  
Ancient Dna ◽  
Dna Sequences ◽  
Estimation Error ◽  
Phylogenetic Analyses ◽  
Published Data ◽  
Molecular Clocks ◽  
Data Sets ◽  
Data Set ◽  
Temporal Sampling ◽  
The Impact

Abstract In recent years, ancient DNA has increasingly been used for estimating molecular timescales, particularly in studies of substitution rates and demographic histories. Molecular clocks can be calibrated using temporal information from ancient DNA sequences. This information comes from the ages of the ancient samples, which can be estimated by radiocarbon dating the source material or by dating the layers in which the material was deposited. Both methods involve sources of uncertainty. The performance of Bayesian phylogenetic inference depends on the information content of the data set, which includes variation in the DNA sequences and the structure of the sample ages. Various sources of estimation error can reduce our ability to estimate rates and timescales accurately and precisely. We investigated the impact of sample-dating uncertainties on the estimation of evolutionary timescale parameters using the software BEAST. Our analyses involved 11 published data sets and focused on estimates of substitution rate and root age. We show that, provided that samples have been accurately dated and have a broad temporal span, it might be unnecessary to account for sample-dating uncertainty in Bayesian phylogenetic analyses of ancient DNA. We also investigated the sample size and temporal span of the ancient DNA sequences needed to estimate phylogenetic timescales reliably. Our results show that the range of sample ages plays a crucial role in determining the quality of the results but that accurate and precise phylogenetic estimates of timescales can be made even with only a few ancient sequences. These findings have important practical consequences for studies of molecular rates, timescales, and population dynamics.

scholarly journals Virus-like insertions with sequence signatures similar to those of endogenous nonretroviral RNA viruses in the human genome

2021 ◽  
Vol 118 (5) ◽  
pp. e2010758118
Author(s):  
Shohei Kojima ◽  
Kohei Yoshikawa ◽  
Jumpei Ito ◽  
So Nakagawa ◽  
Nicholas F. Parrish ◽  
...  
Keyword(s):  
Human Genome ◽  
Viral Infections ◽  
Rna Virus ◽  
Genetic Characteristics ◽  
Origin And Evolution ◽  
Endogenous Viruses ◽  
Evolutionary Features ◽  
Exogenous Origin ◽  
Viral Sequences ◽  
Sequence Signatures

Understanding the genetics and taxonomy of ancient viruses will give us great insights into not only the origin and evolution of viruses but also how viral infections played roles in our evolution. Endogenous viruses are remnants of ancient viral infections and are thought to retain the genetic characteristics of viruses from ancient times. In this study, we used machine learning of endogenous RNA virus sequence signatures to identify viruses in the human genome that have not been detected or are already extinct. Here, we show that the k-mer occurrence of ancient RNA viral sequences remains similar to that of extant RNA viral sequences and can be differentiated from that of other human genome sequences. Furthermore, using this characteristic, we screened RNA viral insertions in the human reference genome and found virus-like insertions with phylogenetic and evolutionary features indicative of an exogenous origin but lacking homology to previously identified sequences. Our analysis indicates that animal genomes still contain unknown virus-derived sequences and provides a glimpse into the diversity of the ancient virosphere.

scholarly journals Mutations as Missing Data: Inferences on the Ages and Distributions of Nonsynonymous and Synonymous Mutations

Genetics ◽  
2001 ◽  
Vol 159 (1) ◽  
pp. 401-411
Author(s):  
Rasmus Nielsen
Keyword(s):  
Missing Data ◽  
Dna Sequences ◽  
Sequence Data ◽  
Published Data ◽  
Data Sets ◽  
Effective Population ◽  
Gene Genealogy ◽  
Synonymous Mutations ◽  
Dna Sequence Data ◽  
Slightly Deleterious Mutations

AbstractThis article describes a new Markov chain Monte Carlo (MCMC) method applicable to DNA sequence data, which treats mutations in the genealogy as missing data. The method facilitates inferences regarding the age and identity of specific mutations while taking the full complexities of the mutational process in DNA sequences into account. We demonstrate the utility of the method in three applications. First, we demonstrate how the method can be used to make inferences regarding population genetical parameters such as θ (the effective population size times the mutation rate). Second, we show how the method can be used to estimate the ages of mutations in finite sites models and for making inferences regarding the distribution and ages of nonsynonymous and synonymous mutations. The method is applied to two previously published data sets and we demonstrate that in one of the data sets the average age of nonsynonymous mutations is significantly lower than the average age of synonymous mutations, suggesting the presence of slightly deleterious mutations. Third, we demonstrate how the method in general can be used to evaluate the posterior distribution of a function of a mapping of mutations on a gene genealogy. This application is useful for evaluating the uncertainty associated with methods that rely on mapping mutations on a phylogeny or a gene genealogy.

Phylogeny of the water strider genus Aquarius Schellenberg (Heteroptera: Gerridae) based on nuclear and mitochondrial DNA sequences and morphology

2000 ◽  
Vol 31 (1) ◽  
pp. 71-90 ◽  
Author(s):  
Nils Møller Andersen ◽  
Jakob Damgaard ◽  
Felix A.H. Sperling
Keyword(s):  
Dna Sequences ◽  
Sequence Data ◽  
Mitochondrial Gene ◽  
Nuclear Gene ◽  
Molecular Data ◽  
Morphological Data ◽  
Published Data ◽  
Data Sets ◽  
Gene Encoding ◽  
Data Set

AbstractWe examined phylogenetic relationships among gerrid water striders of the genus Aquarius Schellenberg using molecular and morphological characters. The molecular data sets included 780 bp sequence data from the mitochondrial gene encoding cytochrome oxidase subunit I (COI), and 515 bp sequence data from the nuclear gene encoding elongation factor I alpha (EF-1α). The morphological data set was a slightly modified version of a previously published data set. We included all 17 known species and one subspecies of Aquarius as well as five species from three related genera, Gigantometra gigas, Limnoporus esakii, L. rufoscutellatus, Gerris pingreensis, and G. lacustris. Unweighted parsimony analyses of the COI data set gave a single most parsimonious tree (MPT) with a topology quite similar to the morphological tree. Parsimony analyses of the EF-1α data set gave 3 MPT's and a strict consensus of these trees gave a tree with a slightly different topology. A combined analysis of the three data sets gave a single MPT with the same topology as for the morphological data set alone. The phylogeny of Aquarius presented here supports the monophyly of the A. najas, remigis, conformis and paludum species groups as well as previous hypotheses about their relationships. On the other hand, the inclusion of molecular data weakens the support for the monophyly of the genus Aquarius, and questions the specific status of the eastern North American A. nebularis (as separate from A. conformis) and members of the Nearctic A. remigis group. Finally, we discuss the implications of the reconstructed phylogeny in the biogeography and ecological phylogenetics of Aquarius.

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

The Age of Nonsynonymous and Synonymous Mutations in Animal mtDNA and Implications for the Mildly Deleterious Theory

Genetics ◽  
1999 ◽  
Vol 153 (1) ◽  
pp. 497-506 ◽  
Author(s):  
Rasmus Nielsen ◽  
Daniel M Weinreich
Keyword(s):  
Dna Sequences ◽  
Purifying Selection ◽  
Data Sets ◽  
Deleterious Mutations ◽  
Synonymous Mutations ◽  
Weak Evidence ◽  
Mitochondrial Data ◽  
The Mean ◽  
Excess Number ◽  
Neutral Mutations

Abstract McDonald/Kreitman tests performed on animal mtDNA consistently reveal significant deviations from strict neutrality in the direction of an excess number of polymorphic nonsynonymous sites, which is consistent with purifying selection acting on nonsynonymous sites. We show that under models of recurrent neutral and deleterious mutations, the mean age of segregating neutral mutations is greater than the mean age of segregating selected mutations, even in the absence of recombination. We develop a test of the hypothesis that the mean age of segregating synonymous mutations equals the mean age of segregating nonsynonymous mutations in a sample of DNA sequences. The power of this age-of-mutation test and the power of the McDonald/Kreitman test are explored by computer simulations. We apply the new test to 25 previously published mitochondrial data sets and find weak evidence for selection against nonsynonymous mutations.

scholarly journals The Sampling Distribution of Disease-Associated Alleles

Genetics ◽  
1997 ◽  
Vol 147 (4) ◽  
pp. 1855-1861 ◽  
Author(s):  
Montgomery Slatkin ◽  
Bruce Rannala
Keyword(s):  
Low Frequency ◽  
Null Model ◽  
Sampling Distribution ◽  
Death Process ◽  
Published Data ◽  
Data Sets ◽  
Likelihood Functions ◽  
Alternative Hypotheses ◽  
Size Standard ◽  
Birth Death

Abstract A theory is developed that provides the sampling distribution of low frequency alleles at a single locus under the assumption that each allele is the result of a unique mutation. The numbers of copies of each allele is assumed to follow a linear birth-death process with sampling. If the population is of constant size, standard results from theory of birth-death processes show that the distribution of numbers of copies of each allele is logarithmic and that the joint distribution of numbers of copies of k alleles found in a sample of size n follows the Ewens sampling distribution. If the population from which the sample was obtained was increasing in size, if there are different selective classes of alleles, or if there are differences in penetrance among alleles, the Ewens distribution no longer applies. Likelihood functions for a given set of observations are obtained under different alternative hypotheses. These results are applied to published data from the BRCA1 locus (associated with early onset breast cancer) and the factor VIII locus (associated with hemophilia A) in humans. In both cases, the sampling distribution of alleles allows rejection of the null hypothesis, but relatively small deviations from the null model can account for the data. In particular, roughly the same population growth rate appears consistent with both data sets.

scholarly journals Biological Impact of a Large-Scale Genomic Inversion That Grossly Disrupts the Relative Positions of the Origin and Terminus Loci of theStreptococcus pyogenesChromosome

2019 ◽  
Vol 201 (17) ◽  
Author(s):  
Dragutin J. Savic ◽  
Scott V. Nguyen ◽  
Kimberly McCullor ◽  
W. Michael McShan
Keyword(s):  
Dna Sequences ◽  
Parental Strain ◽  
Large Scale ◽  
Galleria Mellonella ◽  
Acute Infection ◽  
Relative Length ◽  
Published Data ◽  
Rich Medium ◽  
Content Type

ABSTRACTA large-scale genomic inversion encompassing 0.79 Mb of the 1.816-Mb-longStreptococcus pyogenesserotype M49 strain NZ131 chromosome spontaneously occurs in a minor subpopulation of cells, and in this report genetic selection was used to obtain a stable lineage with this chromosomal rearrangement. This inversion, which drastically displaces theorisite relative to the terminus, changes the relative length of the replication arms so that one replichore is approximately 0.41 Mb while the other is about 1.40 Mb in length. Genomic reversion to the original chromosome constellation is not observed in PCR-monitored analyses after 180 generations of growth in rich medium. Compared to the parental strain, the inversion surprisingly demonstrates a nearly identical growth pattern in the first phase of the exponential phase, but differences do occur when resources in the medium become limited. When cultured separately in rich medium during prolonged stationary phase or in an experimental acute infection animal model (Galleria mellonella), the parental strain and the invertant have equivalent survival rates. However, when they are coincubated together, bothin vitroandin vivo, the survival of the invertant declines relative to the level for the parental strain. The accompanying aspect of the study suggests that inversions taking place nearoriCalways happen to secure the linkage oforiCto DNA sequences responsible for chromosome partition. The biological relevance of large-scale inversions is also discussed.IMPORTANCEBased on our previous work, we created to our knowledge the largest asymmetric inversion, covering 43.5% of theS. pyogenesgenome. In spite of a drastic replacement of origin of replication and the unbalanced size of replichores (1.4 Mb versus 0.41 Mb), the invertant, when not challenged with its progenitor, showed impressive vitality for growthin vitroand in pathogenesis assays. The mutant supports the existing idea that slightly deleterious mutations can provide the setting for secondary adaptive changes. Furthermore, comparative analysis of the mutant with previously published data strongly indicates that even large genomic rearrangements survive provided that the integrity of theoriCand the chromosome partition cluster is preserved.

scholarly journals High Performance Computational Analysis of Large-scale Proteome Data Sets to Assess Incremental Contribution to Coverage of the Human Genome

2013 ◽  
Vol 12 (6) ◽  
pp. 2858-2868 ◽  
Author(s):  
Nadin Neuhauser ◽  
Nagarjuna Nagaraj ◽  
Peter McHardy ◽  
Sara Zanivan ◽  
Richard Scheltema ◽  
...  
Keyword(s):  
Human Genome ◽  
High Performance ◽  
Large Scale ◽  
Computational Analysis ◽  
Data Sets

Relative testis size and mating systems in anurans: large testis in multiple-male mating in foam-nesting frogs

2011 ◽  
Vol 61 (2) ◽  
pp. 225-238 ◽  
Author(s):  
Wen Bo Liao ◽  
Zhi Ping Mi ◽  
Cai Quan Zhou ◽  
Ling Jin ◽  
Xian Han ◽  
...  
Keyword(s):  
Sperm Competition ◽  
Published Data ◽  
Male Mating ◽  
Data Sets ◽  
Testis Size ◽  
Data Set ◽  
Monogamous Species ◽  
Large Testis ◽  
Testes Size ◽  
Testis Mass

AbstractComparative studies of the relative testes size in animals show that promiscuous species have relatively larger testes than monogamous species. Sperm competition favours the evolution of larger ejaculates in many animals – they give bigger testes. In the view, we presented data on relative testis mass for 17 Chinese species including 3 polyandrous species. We analyzed relative testis mass within the Chinese data set and combining those data with published data sets on Japanese and African frogs. We found that polyandrous foam nesting species have relatively large testes, suggesting that sperm competition was an important factor affecting the evolution of relative testes size. For 4 polyandrous species testes mass is positively correlated with intensity (males/mating) but not with risk (frequency of polyandrous matings) of sperm competition.

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