Transfer Of Genetic Information Research Articles

Bacterial Protein Signatures Identified in Porphyromonas gingivalis Containing-Autophagic Vacuoles Reveal Co-Evolution Between Oral Red/Orange Complex Bacteria and Gut Bacteria.

Modern oral bacterial species present as a concoction of commensal and opportunistic pathogens originating from their evolution in humans. Due to the intricate colonization mechanisms shared amongst oral and gut bacteria, these bacteria have likely evolved together to establish and adapt in the human oro-digestive tract, resulting in the transfer of genetic information. Our liquid chromatography-with-tandem-mass-spectrometry (LC-MS-MS) analyses have revealed protein signatures, Elongation Factor Tu, RagB/SusD nutrient uptake outer membrane protein and DnaK, specifically from Porphyromonas gingivalis -containing autophagic vacuoles isolated from the infected human primary gingival epithelial cells. Interestingly, our Mass-Spectrometry analysis reported similar proteins from closely related oral bacteria, Tannerella forsythia and Prevotella intermedia . In our phylogenetic study of these key protein signatures, we have established that pathogenic oral bacteria share extensive relatedness to each other and gut resident bacteria. We show that in the virulence factors identified from gut bacteria, Elongation Factor Tu and DnaK, there are several structural similarities and conservations with proteins from oral pathogenic bacteria. There are also major similarities in the RagB/SusD proteins of oral bacteria to prominent gut bacteria. These findings not only highlight the shared virulence mechanisms amongst oral bacterial pathogens/pathobionts but also gut bacteria and elucidate their co-evolutions in the human host.

The Origin of RNA and the Formose-Ribose-RNA Pathway.

Prebiotic pre-Darwinian reactions continued throughout biochemical or Darwinian evolution. Early chemical processes could have occurred on Earth between 4.5 and 3.6 billion years ago when cellular life was about to come into being. Pre-Darwinian evolution assumes the development of hereditary elements but does not regard them as self-organizing processes. The presence of biochemical self-organization after the pre-Darwinian evolution did not justify distinguishing between different types of evolution. From the many possible solutions, evolution selected from among those stable reactions that led to catalytic networks, and under gradually changing external conditions produced a reproducible, yet constantly evolving and adaptable, living system. Major abiotic factors included sunlight, precipitation, air, minerals, soil and the Earth's atmosphere, hydrosphere and lithosphere. Abiotic sources of chemicals contributed to the formation of prebiotic RNA, the development of genetic RNA, the RNA World and the initial life forms on Earth and the transition of genRNA to the DNA Empire, and eventually to the multitude of life forms today. The transition from the RNA World to the DNA Empire generated new processes such as oxygenic photosynthesis and the hierarchical arrangement of processes involved in the transfer of genetic information. The objective of this work is to unite earlier work dealing with the formose, the origin and synthesis of ribose and RNA reactions that were published as a series of independent reactions. These reactions are now regarded as the first metabolic pathway.

Combined transcriptomic and metabolomic analysis revealed that pH changes affected the expression of carbohydrate and ribosome biogenesis-related genes in Aspergillus niger SICU-33.

The process of carbohydrate metabolism and genetic information transfer is an important part of the study on the effects of the external environment on microbial growth and development. As one of the most significant environmental parameters, pH has an important effect on mycelial growth. In this study, the effects of environmental pH on the growth and nutrient composition of Aspergillus niger (A. niger) filaments were determined. The pH values of the medium were 5, 7, and 9, respectively, and the molecular mechanism was further investigated by transcriptomics and metabolomics methods. The results showed that pH 5 and 9 significantly inhibited filament growth and polysaccharide accumulation of A. niger. Further, the mycelium biomass of A. niger and the crude polysaccharide content was higher when the medium's pH was 7. The DEGs related to ribosome biogenesis were the most abundant, and the downregulated expression of genes encoding XRN1, RRM, and RIO1 affected protein translation, modification, and carbohydrate metabolism in fungi. The dynamic changes of pargyline and choline were in response to the oxidative metabolism of A. niger SICU-33. The ribophorin_I enzymes and DL-lactate may be important substances related to pH changes during carbohydrate metabolism of A.niger SICU-33. The results of this study provide useful transcriptomic and metabolomic information for further analyzing the bioinformatic characteristics of A. niger and improving the application in ecological agricultural fermentation.

Interspecific transfer of genetic information through polyploid bridges

Hybridization blurs species boundaries and leads to intertwined lineages resulting in reticulate evolution. Polyploidy, the outcome of whole genome duplication (WGD), has more recently been implicated in promoting and facilitating hybridization between polyploid species, potentially leading to adaptive introgression. However, because polyploid lineages are usually ephemeral states in the evolutionary history of life it is unclear whether WGD-potentiated hybridization has any appreciable effect on their diploid counterparts. Here, we develop a model of cytotype dynamics within mixed-ploidy populations to demonstrate that polyploidy can in fact serve as a bridge for gene flow between diploid lineages, where introgression is fully or partially hampered by the species barrier. Polyploid bridges emerge in the presence of triploid organisms, which despite critically low levels of fitness, can still allow the transfer of alleles between diploid states of independently evolving mixed-ploidy species. Notably, while marked genetic divergence prevents polyploid-mediated interspecific gene flow, we show that increased recombination rates can offset these evolutionary constraints, allowing a more efficient sorting of alleles at higher-ploidy levels before introgression into diploid gene pools. Additionally, we derive an analytical approximation for the rate of gene flow at the tetraploid level necessary to supersede introgression between diploids with nonzero introgression rates, which is especially relevant for plant species complexes, where interspecific gene flow is ubiquitous. Altogether, our results illustrate the potential impact of polyploid bridges on the (re)distribution of genetic material across ecological communities during evolution, representing a potential force behind reticulation.

Replisome Proximal Protein Associations and Dynamic Proteomic Changes at Stalled Replication Forks

DNA replication is a fundamental cellular process that ensures the transfer of genetic information during cell division. Genome duplication takes place in S phase and requires a dynamic and highly coordinated recruitment of multiple proteins at replication forks. Various genotoxic stressors lead to fork instability and collapse, hence the need for DNA repair pathways. By identifying the multitude of protein interactions implicated in those events, we can better grasp the complex and dynamic molecular mechanisms that facilitate DNA replication and repair. Proximity-dependent biotin identification was used to identify associations with 17 proteins within four core replication components, namely the CDC45/MCM2-7/GINS helicase that unwinds DNA, the DNA polymerases, replication protein A subunits, and histone chaperones needed to disassemble and reassemble chromatin. We further investigated the impact of genotoxic stress on these interactions. This analysis revealed a vast proximity association network with 108 nuclear proteins further modulated in the presence of hydroxyurea; 45 being enriched and 63 depleted. Interestingly, hydroxyurea treatment also caused a redistribution of associations with 11 interactors, meaning that the replisome is dynamically reorganized when stressed. The analysis identified several poorly characterized proteins, thereby uncovering new putative players in the cellular response to DNA replication arrest. It also provides a new comprehensive proteomic framework to understand how cells respond to obstacles during DNA replication.

Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria

The rise of antibiotic resistance is a critical public health concern, requiring an understanding of mechanisms that enable bacteria to tolerate antimicrobial agents. Bacteria use diverse strategies, including the amplification of drug-resistance genes. In this paper, we showed that multicopy plasmids, often carrying antibiotic resistance genes in clinical bacteria, can rapidly amplify genes, leading to plasmid-mediated phenotypic noise and transient antibiotic resistance. By combining stochastic simulations of a computational model with high-throughput single-cell measurements of blaTEM-1 expression in Escherichia coli MG1655, we showed that plasmid copy number variability stably maintains populations composed of cells with both low and high plasmid copy numbers. This diversity in plasmid copy number enhances the probability of bacterial survival in the presence of antibiotics, while also rapidly reducing the burden of carrying multiple plasmids in drug-free environments. Our results further support the tenet that multicopy plasmids not only act as vehicles for the horizontal transfer of genetic information between cells but also as drivers of bacterial adaptation, enabling rapid modulation of gene copy numbers. Understanding the role of multicopy plasmids in antibiotic resistance is critical, and our study provides insights into how bacteria can transiently survive lethal concentrations of antibiotics.

Comparison of Transcriptome Differences between Two Rice Cultivars Differing in Cadmium Translocation from Spike-Neck to Grain.

At present, the mechanism of varietal differences in cadmium (Cd) accumulation in rice is not well understood. Two rice cultivars, ZZY (high translocation-high grain Cd) and SJ18 (low translocation-low grain Cd), were used to analyze transcriptome differences in the spike-neck tissue in field trials. The results showed that, compared with ZZY, 22,367 differentially expressed genes (DEGs) were identified in SJ18, including 2941 upregulated and 19,426 downregulated genes. GO analysis enriched 59 downregulated terms, concerning 24 terms enriched for more than 1000 DEGs, including cellular and metabolic processes, biological regulation, localization, catalytic activity, transporter activity, signaling, etc. KEGG enrichment identified 21 significant downregulated pathways, regarding the ribosome, metabolic pathways, biosynthesis of secondary metabolism, signaling transduction, cell membrane and cytoskeleton synthesis, genetic information transfer, amino acid synthesis, etc. Weighted gene co-expression network analysis (WGCNA) revealed that these DEGs could be clustered into five modules. Among them, the yellow module was significantly related to SJ18 with hub genes related to OsHMA and OsActin, whereas the brown module was significantly related to ZZY with hub genes related to mitogen-activated protein kinase (MAPK), CBS, and glutaredoxin. This suggests that different mechanisms are involved in the process of spike-neck-grain Cd translocation among varieties. This study provides new insights into the mechanisms underlying differences in Cd transport among rice varieties.

Starting DNA Synthesis: Initiation Processes during the Replication of Chromosomal DNA in Humans.

The initiation reactions of DNA synthesis are central processes during human chromosomal DNA replication. They are separated into two main processes: the initiation events at replication origins, the start of the leading strand synthesis for each replicon, and the numerous initiation events taking place during lagging strand DNA synthesis. In addition, a third mechanism is the re-initiation of DNA synthesis after replication fork stalling, which takes place when DNA lesions hinder the progression of DNA synthesis. The initiation of leading strand synthesis at replication origins is regulated at multiple levels, from the origin recognition to the assembly and activation of replicative helicase, the Cdc45-MCM2-7-GINS (CMG) complex. In addition, the multiple interactions of the CMG complex with the eukaryotic replicative DNA polymerases, DNA polymerase α-primase, DNA polymerase δ and ε, at replication forks play pivotal roles in the mechanism of the initiation reactions of leading and lagging strand DNA synthesis. These interactions are also important for the initiation of signalling at unperturbed and stalled replication forks, "replication stress" events, via ATR (ATM-Rad 3-related protein kinase). These processes are essential for the accurate transfer of the cells' genetic information to their daughters. Thus, failures and dysfunctions in these processes give rise to genome instability causing genetic diseases, including cancer. In their influential review "Hallmarks of Cancer: New Dimensions", Hanahan and Weinberg (2022) therefore call genome instability a fundamental function in the development process of cancer cells. In recent years, the understanding of the initiation processes and mechanisms of human DNA replication has made substantial progress at all levels, which will be discussed in the review.

Synthetic reversed sequences reveal default genomic states

Pervasive transcriptional activity is observed across diverse species. The genomes of extant organisms have undergone billions of years of evolution, making it unclear whether these genomic activities represent effects of selection or ‘noise’1–4. Characterizing default genome states could help understand whether pervasive transcriptional activity has biological meaning. Here we addressed this question by introducing a synthetic 101-kb locus into the genomes of Saccharomyces cerevisiae and Mus musculus and characterizing genomic activity. The locus was designed by reversing but not complementing human HPRT1, including its flanking regions, thus retaining basic features of the natural sequence but ablating evolved coding or regulatory information. We observed widespread activity of both reversed and native HPRT1 loci in yeast, despite the lack of evolved yeast promoters. By contrast, the reversed locus displayed no activity at all in mouse embryonic stem cells, and instead exhibited repressive chromatin signatures. The repressive signature was alleviated in a locus variant lacking CpG dinucleotides; nevertheless, this variant was also transcriptionally inactive. These results show that synthetic genomic sequences that lack coding information are active in yeast, but inactive in mouse embryonic stem cells, consistent with a major difference in ‘default genomic states’ between these two divergent eukaryotic cell types, with implications for understanding pervasive transcription, horizontal transfer of genetic information and the birth of new genes.

HIV-1 RNA genome packaging: it's G-rated.

A member of the Retroviridae, human immunodeficiency virus type 1 (HIV-1), uses the RNA genome packaged into nascent virions to transfer genetic information to its progeny. The genome packaging step is a highly regulated and extremely efficient process as a vast majority of virus particles contain two copies of full-length unspliced HIV-1 RNA that form a dimer. Thus, during virus assembly HIV-1 can identify and selectively encapsidate HIV-1 unspliced RNA from an abundant pool of cellular RNAs and various spliced HIV-1 RNAs. Several "G" features facilitate the packaging of a dimeric RNA genome. The viral polyprotein Gag orchestrates virus assembly and mediates RNA genome packaging. During this process, Gag preferentially binds unpaired guanosines within the highly structured 5' untranslated region (UTR) of HIV-1 RNA. In addition, the HIV-1 unspliced RNA provides a scaffold that promotes Gag:Gag interactions and virus assembly, thereby ensuring its packaging. Intriguingly, recent studies have shown that the use of different guanosines at the junction of U3 and R as transcription start sites results in HIV-1 unspliced RNA species with 99.9% identical sequences but dramatically distinct 5' UTR conformations. Consequently, one species of unspliced RNA is preferentially packaged over other nearly identical RNAs. These studies reveal how conformations affect the functions of HIV-1 RNA elements and the complex regulation of HIV-1 replication. In this review, we summarize cis- and trans-acting elements critical for HIV-1 RNA packaging, locations of Gag:RNA interactions that mediate genome encapsidation, and the effects of transcription start sites on the structure and packaging of HIV-1 RNA.

Mapmixture: An R package and web app for spatial visualisation of admixture and population structure.

The mapmixture R package and interactive web app are tools to aid visualisation of admixture and population structure in geographic space. The purpose of mapmixture is to enable and encourage molecular ecologists, and in particular population geneticists and phylogeneticists, to plot their admixture, ancestry or assignment results on a map when location information is available. mapmixture accepts data in the format typically generated by admixture analyses and visualises proportions to each genetic cluster per site as pie charts on a projected (optional) map. Combining this site-based map presentation approach with the routine individual-based presentation of admixture (structure) barplots will enhance interpretation of genetic-geographic patterns. Additionally, in the context of science communication, this enables clearer transfer of spatial genetic information to readers or listeners, and especially to audiences that do not have a background in genetics but who are able to use the genetic information as evidence in conservation management. The latest version of mapmixture is available on GitHub (https://github.com/tom-jenkins/mapmixture), which details installation instructions and examples of how to use the package and interactive web app.

Molecular Analysis of Two Endemic Squalius Species: Evidence for Intergeneric Introgression among Cyprinids and Conservation Issues

Conservation of indigenous species, especially endemic ones, is of the utmost importance. Morphological determination of species is usually not sufficient; therefore, molecular phylogenetic analyses of the Illyrian chub, Squalius illyricus, and the Zrmanja chub, Squalius zrmanjae, from the Krka River were performed. For the genetic characterization of the mitochondrial gene cytochrome b and the non-coding nuclear region Cyfun P, 15 specimens from each species were subjected to analysis. The obtained sequences were aligned with similar ones from GenBank to determine the taxonomic and phylogenetic position of these species. The obtained molecular results imply that S. zrmanjae from the Krka River has a nuclear region that resembles Dalmatian rudd, Scardinius dergle. This result implies an introgression event and the transfer of genetic information between the two genera. The investigated species are on the IUCN Red List of Threatened Species, their biological data are scarce, and further investigation and protection are needed.

Effect of the growth and yield attributes of sunflower and chickpea with responseto different doses and methods of Phosphorus Solubilizing Bacteria in combinationwith different Phosphorus levels

A study was conducted on sunflower and chickpea in sandy loam soils during Rabi 2020 at PJTSAU, Rajendranagar, Hyderabad. This study was focused to know the response of the liquid and powdered PSB on growthand yield attributes of sunflower and chickpea. For this experiment the treatment combination includes, different methods (liquid and powdered) and doses (@ 3 and 6 kg ha-1 for soil application and 50 ml L-1 for drenching) of Phosphorus Solubilizing Bacteria (PSB) along with different phosphorus levels. Phosphorus plays a key role in photosynthesis, metabolism of sugars, energy storage and transfer, cell division, cell enlargement and transfer of genetic information. Inoculation with PSB known to produce the growth hormones like Indole - Acetic Acid and Gibberillic Acid which might favour to increase plant height. The results reported that there was a significant effect of PSB on the plant height, Head diameter, number of pods/plant and non-significant effect on plant stand and test weight. Among, all the treatments the highest plant height (124.33 cm) and head diameter (16.23 cm) at maturity stage in sunflower was seen with 75% P + PSB @ 6 kg/ha and the highest plant height (51.13 cm) and number of pods/plant (26.07) at maturity stage in chickpea was seen with 50% P+ PSB @ 6 kg/ha. There was a non significant effect of PSB on plant stand and test weight. With the application of the PSB there was a reduction of the application of the phosphorus fertilizer to the extent of 25% in sunflower and 50% in chickpea.

The central dogma of biological homochirality: How does chiral information propagate in a prebiotic network?

Biological systems are homochiral, raising the question of how a racemic mixture of prebiotically synthesized biomolecules could attain a homochiral state at the network level. Based on our recent results, we aim to address a related question of how chiral information might have flowed in a prebiotic network. Utilizing the crystallization properties of the central ribonucleic acid (RNA) precursor known as ribose-aminooxazoline (RAO), we showed that its homochiral crystals can be obtained from its fully racemic solution on a magnetic mineral surface due to the chiral-induced spin selectivity (CISS) effect [Ozturk et al., arXiv:2303.01394 (2023)]. Moreover, we uncovered a mechanism facilitated by the CISS effect through which chiral molecules, such as RAO, can uniformly magnetize such surfaces in a variety of planetary environments in a persistent manner [Ozturk et al., arXiv:2304.09095 (2023)]. All this is very tantalizing because recent experiments with tRNA analogs demonstrate high stereoselectivity in the attachment of L-amino acids to D-ribonucleotides, enabling the transfer of homochirality from RNA to peptides [Wu et al., J. Am. Chem. Soc. 143, 11836 (2021)]. Therefore, the biological homochirality problem may be reduced to ensuring that a single common RNA precursor (e.g., RAO) can be made homochiral. The emergence of homochirality at RAO then allows for the chiral information to propagate through RNA, then to peptides, and ultimately through enantioselective catalysis to metabolites. This directionality of the chiral information flow parallels that of the central dogma of molecular biology-the unidirectional transfer of genetic information from nucleic acids to proteins [F. H. Crick, in Symposia of the Society for Experimental Biology, Number XII: The Biological Replication of Macromolecules, edited by F. K. Sanders (Cambridge University Press, Cambridge, 1958), pp. 138-163; and F. Crick, Nature 227, 561 (1970)].

Ageing-associated small RNA cargo of extracellular vesicles

ABSTRACT Previous work on murine models and humans demonstrated global as well as tissue-specific molecular ageing trajectories of RNAs. Extracellular vesicles (EVs) are membrane vesicles mediating the horizontal transfer of genetic information between different tissues. We sequenced small regulatory RNAs (sncRNAs) in two mouse plasma fractions at five time points across the lifespan from 2–18 months: (1) sncRNAs that are free-circulating (fc-RNA) and (2) sncRNAs bound outside or inside EVs (EV-RNA). Different sncRNA classes exhibit unique ageing patterns that vary between the fcRNA and EV-RNA fractions. While tRNAs showed the highest correlation with ageing in both fractions, rRNAs exhibited inverse correlation trajectories between the EV- and fc-fractions. For miRNAs, the EV-RNA fraction was exceptionally strongly associated with ageing, especially the miR-29 family in adipose tissues. Sequencing of sncRNAs and coding genes in fat tissue of an independent cohort of aged mice up to 27 months highlighted the pivotal role of miR-29a-3p and miR-29b-3p in ageing-related gene regulation that we validated in a third cohort by RT-qPCR.

Detection of Specific RNA Targets by Multimerization.

Detection of specific RNA targets via amplification-mediated techniques is widely used in fundamental studies and medicine due to essential role of RNA in transfer of genetic information and development of diseases. Here, we report on an approach for detection of RNA targets based on the particular type of isothermal amplification, namely, reaction of nucleic acid multimerization. The proposed technique requires only a single DNA polymerase possessing reverse transcriptase, DNA-dependent DNA polymerase, and strand-displacement activities. Reaction conditions that lead to efficient detection of the target RNAs through multimerization mechanism were determined. The approach was verified by using genetic material of the SARS-CoV-2 coronavirus as a model viral RNA. Reaction of multimerization allowed to differentiate the SARS-CoV-2 RNA-positive samples from the SARS-CoV-2 negative samples with high reliability. The proposed technique allows detection of RNA even in the samples, which were subjected to multiple freezing-thawing cycles.

Nucleosome Breathing Facilitates the Search for Hidden DNA Sites by Pioneer Transcription Factors

Transfer of genetic information starts with transcription factors (TFs) binding to specific sites on DNA. But in living cells, DNA is mostly covered by nucleosomes. There are proteins, known as pioneer TFs, that can efficiently reach the DNA sites hidden by nucleosomes, although the underlying mechanisms are not understood. Using the recently proposed idea of interaction-compensation mechanism, we develop a stochastic model for the target search on DNA with nucleosome breathing. It is found that nucleosome breathing can significantly accelerate the search by pioneer TFs in comparison to situations without breathing. We argue that this is the result of the interaction-compensation mechanism that allows proteins to enter the inner nucleosome region through the outer DNA segment. It is suggested that nature optimized pioneer TFs to take advantage of nucleosome breathing. The presented theoretical picture provides a possible microscopic explanation for the successful invasion of nucleosome-buried genes.

The complexity of transferring genetic information

The Central Dogma has been a useful conceptualization of the transfer of genetic information, and our understanding of the detailed mechanisms involved in that transfer continues to evolve. Here, we speak to several scientists about their research, how it influences our understanding of information transfer, and questions for the future.

Toward understanding the emergence of life: A dual function of the system of nucleotides in the metabolically closed autopoietic organization

General structure of metabolism includes the reproduction of catalysts that govern metabolism. In this structure, the system becomes autopoietic in the sense of Maturana and Varela, and it is closed to efficient causation as defined by Robert Rosen. The autopoietic maintenance and operation of the catalysts takes place via the set of free nucleotides while the synthesis of catalysts occurs via the information encoded by the set of nucleotides arranged in polymers of RNA and DNA. Both energy charge and genetic information use the components of the same pool of nucleoside triphosphates, which is equilibrated by thermodynamic buffering enzymes such as nucleoside diphosphate kinase and adenylate kinase. This occurs in a way that the system becomes internally stable and metabolically closed, which initially could be realized at the level of ribozymes catalyzing basic metabolic reactions as well as own reproduction. The function of ATP, GTP, UTP, and CTP is dual, as these species participate both in the general metabolism as free nucleotides and in the transfer of genetic information via covalent polymerization to nucleic acids. The changes in their pools directly impact both bioenergetic pathways and nucleic acid turnover. Here we outline the concept of metabolic closure of biosystems grounded in the dual function of nucleotide coenzymes that serve both as energetic and informational molecules and through this duality generate the autopoietic performance and the ability for codepoietic evolutionary transformations of living systems starting from the emergence of prebiotic systems.

The position of the longest intron is related to biological functions in some human genes.

The evidence that introns can influence different levels of transfer of genetic information between DNA and the final product is increasing. Longer first introns were found to be a general property of eukaryotic gene structure and shown to contain a higher fraction of conserved sequence and different functional elements. Our work brings more precise information about the position of the longest introns in human protein-coding genes and possible connection with biological function and gene expression. According to our results, the position of the longest intron can be localized to the first third of introns in 64%, the second third in 19%, and the third in 17%, with notable peaks at the middle and last introns of approximately 5% and 6%, respectively. The median lengths of the longest introns decrease with increasing distance from the start of the gene from approximately 15,000 to 5,000bp. We have shown that the position of the longest intron is in some cases linked to the biological function of the given gene. For example, DNA repair genes have the longest intron more often in the second or third. In the distribution of gene expression according to the position of the longest intron, tissue-specific profiles can be traced with the highest expression usually at the absolute positions of intron 1 and 2. In this work, we present arguments supporting the hypothesis that the position of the longest intron in a gene is another biological factor modulating the transmission of genetic information. The position of the longest intron is related to biological functions in some human genes.