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Coronaviruses are large RNA viruses that can infect and spread among humans and animals. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019, has evolved since its first detection in December 2019. Deletions are a common occurrence in SARS-CoV-2 evolution, particularly in specific genomic sites, and may be associated with the emergence of highly competent lineages. While deletions typically have a negative impact on viral fitness, some persist and become fixed in viral populations, indicating that they may confer advantageous benefits for the virus's adaptive evolution. This work presents a literature review and data analysis on structural losses in the SARS-CoV-2 genome and the potential relevance of specific signatures for enhanced viral fitness and spread. [ABSTRACT FROM AUTHOR]

Abstract Background Chloroplast genome sequence data is very useful in studying/addressing the phylogeny of plants at various taxonomic ranks. However, there are no empirical observations on the patterns, directions, and mutation rates, which are the key topics in chloroplast genome evolution. In this study, we used Calycanthaceae as a model to investigate the evolutionary patterns, directions and rates of both nucleotide substitutions and structural mutations at different taxonomic ranks. Results There were 2861 polymorphic nucleotide sites on the five chloroplast genomes, and 98% of polymorphic sites were biallelic. There was a single-nucleotide substitution bias in chloroplast genomes. A → T or T → A (2.84%) and G → C or C → G (3.65%) were found to occur significantly less frequently than the other four transversion mutation types. Synonymous mutations kept balanced pace with nonsynonymous mutations, whereas biased directions appeared between transition and transversion mutations and among transversion mutations. Of the structural mutations, indels and repeats had obvious directions, but microsatellites and inversions were non-directional. Structural mutations increased the single nucleotide mutations rates. The mutation rates per site per year were estimated to be 0.14–0.34 × 10− 9 for nucleotide substitution at different taxonomic ranks, 0.64 × 10− 11 for indels and 1.0 × 10− 11 for repeats. Conclusions Our direct counts of chloroplast genome evolution events provide raw data for correctly modeling the evolution of sequence data for phylogenetic inferences.

Abstract Background Many neurodegenerative diseases are caused by nucleotide repeat expansions, but most expansions, like the C9orf72 ‘GGGGCC’ (G4C2) repeat that causes approximately 5–7% of all amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases, are too long to sequence using short-read sequencing technologies. It is unclear whether long-read sequencing technologies can traverse these long, challenging repeat expansions. Here, we demonstrate that two long-read sequencing technologies, Pacific Biosciences’ (PacBio) and Oxford Nanopore Technologies’ (ONT), can sequence through disease-causing repeats cloned into plasmids, including the FTD/ALS-causing G4C2 repeat expansion. We also report the first long-read sequencing data characterizing the C9orf72 G4C2 repeat expansion at the nucleotide level in two symptomatic expansion carriers using PacBio whole-genome sequencing and a no-amplification (No-Amp) targeted approach based on CRISPR/Cas9. Results Both the PacBio and ONT platforms successfully sequenced through the repeat expansions in plasmids. Throughput on the MinION was a challenge for whole-genome sequencing; we were unable to attain reads covering the human C9orf72 repeat expansion using 15 flow cells. We obtained 8× coverage across the C9orf72 locus using the PacBio Sequel, accurately reporting the unexpanded allele at eight repeats, and reading through the entire expansion with 1324 repeats (7941 nucleotides). Using the No-Amp targeted approach, we attained > 800× coverage and were able to identify the unexpanded allele, closely estimate expansion size, and assess nucleotide content in a single experiment. We estimate the individual’s repeat region was > 99% G4C2 content, though we cannot rule out small interruptions. Conclusions Our findings indicate that long-read sequencing is well suited to characterizing known repeat expansions, and for discovering new disease-causing, disease-modifying, or risk-modifying repeat expansions that have gone undetected with conventional short-read sequencing. The PacBio No-Amp targeted approach may have future potential in clinical and genetic counseling environments. Larger and deeper long-read sequencing studies in C9orf72 expansion carriers will be important to determine heterogeneity and whether the repeats are interrupted by non-G4C2 content, potentially mitigating or modifying disease course or age of onset, as interruptions are known to do in other repeat-expansion disorders. These results have broad implications across all diseases where the genetic etiology remains unclear.

Background: Chloroplast genome sequence data is very useful in studying/addressing the phylogeny of plants at various taxonomic ranks. However, there are no empirical observations on the patterns, directions, and mutation rates, which are the key topics in chloroplast genome evolution. In this study, we used Calycanthaceae as a model to investigate the evolutionary patterns, directions and rates of both nucleotide substitutions and structural mutations at different taxonomic ranks. Results: There were 2861 polymorphic nucleotide sites on the five chloroplast genomes, and 98% of polymorphic sites were biallelic. There was a single-nucleotide substitution bias in chloroplast genomes. A → T or T → A (2.84%) and G → C or C → G (3.65%) were found to occur significantly less frequently than the other four transversion mutation types. Synonymous mutations kept balanced pace with nonsynonymous mutations, whereas biased directions appeared between transition and transversion mutations and among transversion mutations. Of the structural mutations, indels and repeats had obvious directions, but microsatellites and inversions were non-directional. Structural mutations increased the single nucleotide mutations rates. The mutation rates per site per year were estimated to be 0.14–0.34 × 10− 9 for nucleotide substitution at different taxonomic ranks, 0.64 × 10− 11 for indels and 1.0 × 10− 11 for repeats. Conclusions: Our direct counts of chloroplast genome evolution events provide raw data for correctly modeling the evolution of sequence data for phylogenetic inferences. [ABSTRACT FROM AUTHOR]

Coronaviruses are large RNA viruses that can infect and spread among humans and animals. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019, has evolved since its first detection in December 2019. Deletions are a common occurrence in SARS-CoV-2 evolution, particularly in specific genomic sites, and may be associated with the emergence of highly competent lineages. While deletions typically have a negative impact on viral fitness, some persist and become fixed in viral populations, indicating that they may confer advantageous benefits for the virus's adaptive evolution. This work presents a literature review and data analysis on structural losses in the SARS-CoV-2 genome and the potential relevance of specific signatures for enhanced viral fitness and spread., Competing Interests: The authors declare no conflict of interest.

Over the years, numerous groups have employed human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) as a superb human-compatible model for investigating the function and dysfunction of cardiomyocytes, drug screening and toxicity, disease modeling and for the development of novel drugs for heart diseases. In this review, we discuss the broad use of iPSC-CMs for drug development and disease modeling, in two related themes. In the first theme—drug development, adverse drug reactions, mechanisms of cardiotoxicity and the need for efficient drug screening protocols—we discuss the critical need to screen old and new drugs, the process of drug development, marketing and Adverse Drug reactions (ADRs), drug-induced cardiotoxicity, safety screening during drug development, drug development and patient-specific effect and different mechanisms of ADRs. In the second theme—using iPSC-CMs for disease modeling and developing novel drugs for heart diseases—we discuss the rationale for using iPSC-CMs and modeling acquired and inherited heart diseases with iPSC-CMs.

There are numerous papers and studies devoted to Romanian loanwords which were adopted by Romanian speakers from English. Some of these words are useful and denominate realities for which the Romanian language does not have a formal and semantic equivalent, while others have a perfectly functional equivalent in Romanian, being thus unnecessary borrowings used especially out of snobbism. The present paper aims at going beyond individual words by exploring more complex lexical structures such as collocations and idioms. Borrowing such complex lexical structures, the so called ‘chunks of language’ or ’prefabricated structures’, from English is a relatively new phenomenon in Romanian. There are not too many such structures, but the Romanian speakers who tend to integrate them in their speech have two easily noticeable problems, i.e. they either use them in the wrong context or try to adapt them to collocations already existing in Romanian, thus making them sound strange, to say the least. The examples analysed in this paper are meant to illustrate how the phenomenon/phenomena of ”lexical mutation” and/or ”structural mutation” make the collocations and idioms borrowed from English sound awkward and inappropriate in Romanian. [ABSTRACT FROM AUTHOR]

he global economic crisis had most negative effects on the entire economic sphere and especially in what the consuming industry is concerned, which may be considered “luxurious”, the way in which we may talk about the furniture industry. Along times of economic crisis at social level, a decrease in financial power at microeconomic, individual level is felt. Under conditions of social decrease in buying capacity, the request for commercial furniture is in rapid fall and thus the industry as such suffers serious structural mutations. Analyzing a series of macroeconomic indices from the European furniture industry led to the result that during the late years there has been a positive trend within the furniture industry in matters of production, however, with concern to trading, the situation is more complicated. There is a behaviour difference in the furniture industry between emergent countries and EU developed states and based on the performed analysis, a SWOT analysis at sectorial level crystallized, in which we propose ways of growth in the European furniture industry.

Evolutionary dynamics of structural genetic variation in lineages of hybrid origin is not well explored, although structural mutations may increase in controlled hybrid crosses. We therefore tested whether structural variants accumulate in a fish of recent hybrid origin, invasive Cottus, relative to both parental species Cottus rhenanus and Cottus perifretum. Copy-number variation in exons of 10,979 genes was assessed using comparative genome hybridization arrays. Twelve genes showed significantly higher copy numbers in invasive Cottus compared to both parents. This coincided with increased expression for three genes related to vision, detoxification and muscle development, suggesting possible gene dosage effects. Copy number increases of putative transposons were assessed by comparative mapping of genomic DNA reads against a de novo assembly of 1,005 repetitive elements. In contrast to exons, copy number increases of repetitive elements were common (20.7%) in invasive Cottus, whereas decrease was very rare (0.01%). Among the increased repetitive elements, 53.8% occurred at higher numbers in C. perifretum compared to C. rhenanus, while only 1.4% were more abundant in C. rhenanus. This implies a biased mutational process that amplifies genetic material from one ancestor. To assess the frequency of de novo mutations through hybridization, we screened 64 laboratory-bred F2 offspring between the parental species for copy-number changes at five candidate loci. We found no evidence for new structural variants, indicating that they are too rare to be detected given our sampling scheme. Instead, they must have accumulated over more generations than we observed in a controlled cross. [ABSTRACT FROM AUTHOR]

Background Structural mutations (SMs) play a major role in cancer development. In some cancers, such as breast and ovarian, DNA double-strand breaks (DSBs) occur more frequently in transcribed regions, while in other cancer types such as prostate, there is a consistent depletion of breakpoints in transcribed regions. Despite such regularity, little is understood about the mechanisms driving these effects. A few works have suggested that protein binding may be relevant, e.g. in studies of androgen receptor binding and active chromatin in specific cell types. We hypothesized that this behavior might be general, i.e. that correlation between protein-DNA binding (and open chromatin) and breakpoint locations is common across divergent cancers. Results We investigated this hypothesis by comprehensively analyzing the relationship among 457 ENCODE protein binding ChIP-seq experiments, 125 DnaseI and 24 FAIRE experiments, and 14,600 SMs from 8 diverse cancer datasets covering 147 samples. In most cancers, including breast and ovarian, we found enrichment of protein binding and open chromatin in the vicinity of SM breakpoints at distances up to 200 kb. Furthermore, for all cancer types we observed an enhanced enrichment in regions distant from genes when compared to regions proximal to genes, suggesting that the SM-induction mechanism is independent from the bias of DSBs to occur near transcribed regions. We also observed a stronger effect for sites with more than one protein bound. Conclusions Protein binding and open chromatin state are associated with nearby SM breakpoints in many cancer datasets. These observations suggest a consistent mechanism underlying SM locations across different cancers. [ABSTRACT FROM AUTHOR]

Proteins change over the course of evolutionary time. New protein-coding genes and gene families emerge and diversify, ultimately affecting an organism’s phenotype and interactions with its environment. Here we survey the range of structural protein change observed in plants and review the role these changes have had in the evolution of plant form and function. Verified examples tying evolutionary change in protein structure to phenotypic change remain scarce. We will review the existing examples, as well as draw from investigations into domestication, and quantitative trait locus (QTL) cloning studies searching for the molecular underpinnings of natural variation. The evolutionary significance of many cloned QTL has not been assessed, but all the examples identified so far have begun to reveal the extent of protein structural diversity tolerated in natural systems. This molecular (and phenotypic) diversity could come to represent part of natural selection’s source material in the adaptive evolution of novel traits. Protein structure and function can change in many distinct ways, but the changes we identified in studies of natural diversity and protein evolution were predicted to fall primarily into one of six categories: altered active and binding sites; hypomorphic and hypermorphic alleles; altered protein-protein interactions; altered domain content; altered protein stability; and altered activity as an activator or repressor. Variability was also observed in the evolutionary scale at which particular changes were observed. Some changes were detected at both micro- and macroevolutionary timescales, while others were observed primarily at deep or shallow phylogenetic levels. This variation might be used to determine the trajectory of future investigations in structural molecular evolution.

Proteins change over the course of evolutionary time. New protein-coding genes and gene families emerge and diversify, ultimately affecting an organism's phenotype and interactions with its environment. Here we survey the range of structural protein change observed in plants and review the role these changes have had in the evolution of plant form and function. Verified examples tying evolutionary change in protein structure to phenotypic change remain scarce. We will review the existing examples, as well as draw from investigations into domestication, and quantitative trait locus (QTL) cloning studies searching for the molecular underpinnings of natural variation. The evolutionary significance of many cloned QTL has not been assessed, but all the examples identified so far have begun to reveal the extent of protein structural diversity tolerated in natural systems. This molecular (and phenotypic) diversity could come to represent part of natural selection's source material in the adaptive evolution of novel traits. Protein structure and function can change in many distinct ways, but the changes we identified in studies of natural diversity and protein evolution were predicted to fall primarily into one of six categories: altered active and binding sites; altered protein-protein interactions; altered domain content; altered activity as an activator or repressor; altered protein stability; and hypomorphic and hypermorphic alleles.There was also variability in the evolutionary scale at which particular changes were observed. Some changes were detected at both micro- and macroevolutionary timescales, while others were observed primarily at deep or shallow phylogenetic levels. This variation might be used to determine the trajectory of future investigations in structural molecular evolution. [ABSTRACT FROM AUTHOR]

Non-functional trnF pseudogenes that rarely occur in embryophytes have been found in Solanaceae. We have sequenced the trnL-F intergenic spacer of four species of Solanum, and found duplicated regions of the original trnF gene. These repeats were 94-260 bp long causing large length variation in the trnL-F intergenic spacer resulting from differences in pseudogene copy number (2-4). The duplicated trnF regions are comprised of several highly structured motifs, which were partial residues, or entire parts of the Anticodon, T- and D-domains of the original gene, but all lacked the acceptor stems at the 5′- or 3′-end. Pseudogenes included several transitions and transversions in their sequences compared to the original trnF gene. Among pseudogene copies, T-domains were more frequent and fragmented than D-domain elements. Our results demonstrate that although chloroplast evolution is uniform such structural duplications in the sequences used for phylogenetic reconstructions should be treated with great caution. [ABSTRACT FROM AUTHOR]

Over the years, numerous groups have employed human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) as a superb human-compatible model for investigating the function and dysfunction of cardiomyocytes, drug screening and toxicity, disease modeling and for the development of novel drugs for heart diseases. In this review, we discuss the broad use of iPSC-CMs for drug development and disease modeling, in two related themes. In the first theme—drug development, adverse drug reactions, mechanisms of cardiotoxicity and the need for efficient drug screening protocols—we discuss the critical need to screen old and new drugs, the process of drug development, marketing and Adverse Drug reactions (ADRs), drug-induced cardiotoxicity, safety screening during drug development, drug development and patient-specific effect and different mechanisms of ADRs. In the second theme—using iPSC-CMs for disease modeling and developing novel drugs for heart diseases—we discuss the rationale for using iPSC-CMs and modeling acquired and inherited heart diseases with iPSC-CMs. [ABSTRACT FROM AUTHOR]