Conservation Patterns Research Articles

Thallium and lead variations in a contaminated peatland: A combined isotopic study from a mining/smelting area

Vertical profiles of Tl, Pb and Zn concentrations and Tl and Pb isotopic ratios in a contaminated peatland/fen (Wolbrom, Poland) were studied to address questions regarding (i) potential long-term immobility of Tl in a peat profile, and (ii) a possible link in Tl isotopic signatures between a Tl source and a peat sample. Both prerequisites are required for using peatlands as archives of atmospheric Tl deposition and Tl isotopic ratios as a source proxy. We demonstrate that Tl is an immobile element in peat with a conservative pattern synonymous to that of Pb, and in contrast to Zn. However, the peat Tl record was more affected by geogenic source(s), as inferred from the calculated element enrichments. The finding further implies that Tl was largely absent from the pre-industrial emissions (>~250 years BP). The measured variations in Tl isotopic ratios in respective peat samples suggest a consistency with anthropogenic Tl (ε205Tl between ~ -3 and −4), as well as with background Tl isotopic values in the study area (ε205Tl between ~0 and −1), in line with detected 206Pb/207Pb ratios (1.16–1.19). Therefore, we propose that peatlands can be used for monitoring trends in Tl deposition and that Tl isotopic ratios can serve to distinguish its origin(s). However, given that the studied fen has a particularly complicated geochemistry (attributed to significant environmental changes in its history), it seems that ombrotrophic peatlands could be better suited for this type of Tl research.

The Oldest Co-opted gag Gene of a Human Endogenous Retrovirus Shows Placenta-Specific Expression and Is Upregulated in Diffuse Large B-Cell Lymphomas.

Vertebrate genomes contain endogenous retroviruses (ERVs) that represent remnants of past germline infections by ancient retroviruses. Despite comprising 8% of the human genome, the human ERVs (HERVs) do not encode a replication competent retrovirus. However, some HERV genes have been co-opted to serve host functions, most notably the viral envelope-derived syncytins involved in placentation. Here, we identify the oldest HERV intact gag gene with an open reading frame, gagV1. Its provirus contains an intact env, envV1, and the first open reading frame found in an HERV gag leader, pre-gagV1, which encodes a novel protein. This HERV is linked to a related gag gene, gagV3, and these three genes all show patterns of evolutionary conservation in primates. gagV1 and pre-gagV1 orthologs are present in all simian primate lineages indicating that this HERV entered the germline of the common simian primate ancestor at least 43 Ma, whereas gagV3 is found in Old and New World monkeys. gagV1 and gagV3 have undergone recurrent gene conversion events and positive selection. Expression of gagV1, gagV3, and pre-gagV1 is restricted to the placenta in humans and macaques suggesting co-option for placenta-specific host functions. Transcriptomic analysis of human tumors also found upregulated levels of gagV1 transcripts in diffuse large B-cell lymphomas. These findings suggest that these HERV-V genes may be useful markers for the most common type of non-Hodgkin's lymphoma and that they may have contributed to the successive domestications of env and gag genes in eutherians involved in the ongoing ERV-driven evolution of the placenta.

Sparse generative modeling via parameter reduction of Boltzmann machines: Application to protein-sequence families.

Boltzmann machines (BMs) are widely used as generative models. For example, pairwise Potts models (PMs), which are instances of the BM class, provide accurate statistical models of families of evolutionarily related protein sequences. Their parameters are the local fields, which describe site-specific patterns of amino acid conservation, and the two-site couplings, which mirror the coevolution between pairs of sites. This coevolution reflects structural and functional constraints acting on protein sequences during evolution. The most conservative choice to describe the coevolution signal is to include all possible two-site couplings into the PM. This choice, typical of what is known as Direct Coupling Analysis, has been successful for predicting residue contacts in the three-dimensional structure, mutational effects, and generating new functional sequences. However, the resulting PM suffers from important overfitting effects: many couplings are small, noisy, and hardly interpretable; the PM is close to a critical point, meaning that it is highly sensitive to small parameter perturbations. In this work, we introduce a general parameter-reduction procedure for BMs, via a controlled iterative decimation of the less statistically significant couplings, identified by an information-based criterion that selects either weak or statistically unsupported couplings. For several protein families, our procedure allows one to remove more than 90% of the PM couplings, while preserving the predictive and generative properties of the original dense PM, and the resulting model is far away from criticality, hence more robust to noise.

Spatial and temporal evolution characteristics of the water conservation function and its driving factors in regional lake wetlands—Two types of homogeneous lakes as examples

Water conservation is the core wetland ecological function. The pattern of water conservation in geography often exhibits local spatial heterogeneity. In this paper, the Dongting Lake (DT) and Poyang Lake (PY) wetlands were taken as research objects, and the water yield (WY) module of the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model was used to spatially quantify water conservation, with the aim of revealing the differences in water conservation in homogeneous wetlands. We observed spatio-temporal changes in the WY over six periods from 1998 to 2018 and used multivariate analysis of variance (MANOVA) and the system cluster method to explore the patterns and driving factors of water conservation in the DT and PY wetlands. The research results were as follows: (1) the WY in the two wetlands showed declining trends, but the trend in the DT wetland was more obvious. (2) Water conservation in the PY wetland exhibited a more sensitive response to climate than water conservation in the DT wetland. (3) From the perspective of the WY level, the PY wetland was generally high, while the DT wetland was generally low. (4) Climate change was the main contributor to and direct driving factor of water production, while wetland changes and socio-economic factors were indirect driving factors. (5) The effect of wetland cover changes on the WY showed significant differences among wetland cover types, indicating that the drivers of the WY changes had a clear relationship with landscape changes and transfers in wetland cover types. (6) The InVEST model was applicable for evaluating lake wetland water conservation. In summary, paying more attention to the differences in the changes in heterogeneous and homogenous regions can help us understand the factors that impact water conservation. Additionally, rational adjustment of indirect driving forces is conducive to ecological safety management.

Channeling of Carbon Flux Towards Carotenogenesis in Botryococcus braunii: A Media Engineering Perspective

Microalgae, due to their unique properties, gained attention for producing promising feedstocks having high contents of proteins, antioxidants, carotenoids, and terpenoids for applications in nutraceutical and pharmaceutical industries. Optimizing production of the high-value renewables (HVRs) in microalgae requires an in-depth understanding of their functional relationship of the genes involved in these metabolic pathways. In the present study, bioinformatic tools were employed for characterization of the protein-encoding genes of methyl erythritol phosphate (MEP) pathway involved in carotenoid and squalene biosynthesis based upon their conserved motif/domain organization. Our analysis demonstrates nearly 200 putative genes showing a conservation pattern within divergent microalgal lineages. Furthermore, phylogenomic studies confirm the close evolutionary proximity among these microalgal strains in the carotenoid and squalene biosynthetic pathways. Further analysis employing STRING predicts interactions among two rate-limiting genes, i.e., phytoene synthase (PSY) and farnesyl diphosphate farnesyl synthase (FPPS), which are specifically involved in the synthesis of carotenoids and squalene. Experimentally, to understand the carbon flux of these rate-limiting genes involved in carotenogenesis, an industrial potential strain, namely, Botryococcus braunii, was selected in this study for improved biomass productivity (i.e., 100 mg L–1 D–1) along with enhanced carotenoid content [0.18% dry cell weight (DCW)] when subjected to carbon supplementation. In conclusion, our approach of media engineering demonstrates that the channeling of carbon flux favors carotenogenesis rather than squalene synthesis. Henceforth, employing omics perspectives will further provide us with new insights for engineering regulatory networks for enhanced production of high-value carbon biorenewables without compromising growth.

Genome-Wide Identification and Characterization of Amino Acid Polyamine Organocation Transporter Family Genes Reveal Their Role in Fecundity Regulation in a Brown Planthopper Species (Nilaparvata lugens).

The brown planthopper (BPH), Nilaparvata lugens Stål (Hemiptera:Delphacidae), is one of the most destructive pests of rice worldwide. As a sap-feeding insect, the BPH is incapable of synthesizing several amino acids which are essential for normal growth and development. Therefore, the insects have to acquire these amino acids from dietary sources or their endosymbionts, in which amino acid transporters (AATs) play a crucial role by enabling the movement of amino acids into and out of insect cells. In this study, a common amino acid transporter gene family of amino acid/polyamine/organocation (APC) was identified in BPHs and analyzed. Based on a homology search and conserved functional domain recognition, 20 putative APC transporters were identified in the BPH genome. Molecular trait analysis showed that the verified BPH APC family members were highly variable in protein features, conserved motif distribution patterns, and exon/intron organization. Phylogenetic analysis of five hemipteran species revealed an evolutionary pattern of interfamily conservation and lineage-specific expansion of this gene family. Moreover, stage- and tissue-specific expression analysis revealed diverse expression patterns in the 20 BPH APC transporter genes. Lastly, a potential BPH fecundity regulatory gene of NlAPC09 was identified and shown to participate in the fecundity regulation through the use of quantitative polymerase chain reaction (qPCR) and RNA inference experiments. Our results provide a basis for further functional investigations of APC transporters in BPH.

Variation in the Evolution and Sequences of Proglucagon and the Receptors for Proglucagon-Derived Peptides in Mammals.

The mammalian proglucagon gene (Gcg) encodes three glucagon like sequences, glucagon, glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 that are of similar length and share sequence similarity, with these hormones having cell surface receptors, glucagon receptor (Gcgr), GLP-1 receptor (Glp1r), and GLP-2 receptor (Glp2r), respectively. Gcgr, Glp1r, and Glp2r are all class B1 G protein-coupled receptors (GPCRs). Despite their sequence and structural similarity, analyses of sequences from rodents have found differences in patterns of sequence conservation and evolution. To determine whether these were rodent-specific traits or general features of these genes in mammals I analyzed coding and protein sequences for proglucagon and the receptors for proglucagon-derived peptides from the genomes of 168 mammalian species. Single copy genes for each gene were found in almost all genomes. In addition to glucagon sequences within Hystricognath rodents (e.g., guinea pig), glucagon sequences from a few other groups (e.g., pangolins and some bats) as well as changes in the proteolytic processing of GLP-1 in some bats are suggested to have functional effects. GLP-2 sequences display increased variability but accepted few substitutions that are predicted to have functional consequences. In parallel, Glp2r sequences display the most rapid protein sequence evolution, and show greater variability in amino acids at sites involved in ligand interaction, however most were not predicted to have a functional consequence. These observations suggest that a greater diversity in biological functions for proglucagon-derived peptides might exist in mammals.

Comparative Transcriptomics Reveals Distinct Patterns of Gene Expression Conservation through Vertebrate Embryogenesis.

Despite life’s diversity, studies of variation often remind us of our shared evolutionary past. Abundant genome sequencing and analyses of gene regulatory networks illustrate that genes and entire pathways are conserved, reused, and elaborated in the evolution of diversity. Predating these discoveries, 19th-century embryologists observed that though morphology at birth varies tremendously, certain stages of vertebrate embryogenesis appear remarkably similar across vertebrates. In the mid to late 20th century, anatomical variability of early and late-stage embryos and conservation of mid-stages embryos (the “phylotypic” stage) was named the hourglass model of diversification. This model has found mixed support in recent analyses comparing gene expression across species possibly owing to differences in species, embryonic stages, and gene sets compared. We compare 186 microarray and RNA-seq data sets covering embryogenesis in six vertebrate species. We use an unbiased clustering approach to group stages of embryogenesis by transcriptomic similarity and ask whether gene expression similarity of clustered embryonic stages deviates from a null expectation. We characterize expression conservation patterns of each gene at each evolutionary node after correcting for phylogenetic nonindependence. We find significant enrichment of genes exhibiting early conservation, hourglass, late conservation patterns in both microarray and RNA-seq data sets. Enrichment of genes showing patterned conservation through embryogenesis indicates diversification of embryogenesis may be temporally constrained. However, the circumstances under which each pattern emerges remain unknown and require both broad evolutionary sampling and systematic examination of embryogenesis across species.

A RADICAL GRADIENT FOR RESEARCH AMONG REHABILITATION PROFESSIONALS

Revolution in practice is required among the professionals of rehab members in holistic team while working parallel with each other for inhibition, development, refurbishment and decline of functioning among clients along with effective service delivery system. This describes the focus of rehab professional on the International Classification of Functioning, Disability and Health (ICD) model of disability. Rehab professionals move from lab to clinical practice and community is actually an interchange of conservative investigation pattern to translational research mode, not just the implementing research outcome but also evolving the guidelines for healthier service model. Professional locally has understood the significance of evidence based practiced though the carter to attain translational research is still at T1 and T2 phase which is from bench to bedside. Mostly the research activities involves around the implementation of knowledge in to practice or combination of effective interventions. Among the rehab professionals the pace of evidence based practiced is faster among the physiotherapist whereas the other members of team such as Occupational therapist, speech therapist and psychotherapist are at very initial stage. It could be the curriculum advancement, unavailability of learning resources and lack of professional awareness not only in general population but also among the health care provider.

Global patterns of extinction risk and conservation needs for Rodentia and Eulipotyphla

AbstractAimTo explore global patterns in spatial aggregations of species richness, vulnerability and data deficiency for Rodentia and Eulipotyphla. To evaluate the adequacy of existing protected area (PA) network for these areas. To provide a focus for local conservation initiatives.LocationGlobal.MethodsTotal species, globally threatened (GT) species, and Data Deficient (DD) species richness were calculated for a 1° resolution grid. Correspondence analyses between global species richness against GT species richness were performed. To assess PA network adequacy, a correspondence analysis was conducted to identify areas of high richness and GT species richness that have poor protection.ResultsSix hotspots were identified for GT eulipotyphlans, encompassing 40% of GT species. Three of these contain higher numbers of GT species than would be expected based on their overall species richness. Ten priority regions were identified for GT rodents, which together contain 34% of all GT species. Six contain higher numbers of GT rodent species than would be expected based on their overall species richness. For DD species, 15% of DD eulipotyphlans were represented within three priority regions, whereas 18 were identified for rodents, capturing 53% of all DD species. Areas containing lower numbers of protected GT eulipotyphlan species than expected include Mexico; Cameroonian Highlands; Albertine Rift; Tanzania; Kenya; Ethiopia; western Asia; India; and Sri Lanka. Areas containing lower numbers of protected GT rodent species than expected are Borneo, Sumatra and Sulawesi. Five eulipotyphlans and 44 rodents have ranges which fall completely outside of PAs.Main conclusionRodentia and Eulipotyphla priority regions should be considered separately to one another and to other mammals. This analysis approach allows us to pinpoint and delineate geographical areas which represent key regions at a global level for rodents and eulipotyphlans, in order to facilitate conservation, field research and capacity building at a local level.

Higher education in Soviet and Russian welfare states: hybridization, continuity and change

ABSTRACT This research explores the interrelations of higher education and welfare state models in the USSR of the 1960-1980s and Russia of the 2000-2020s. We first address the extent to which the provision of higher education aligns with the key imperatives of welfare redistribution: eligibility, state-market balance, and equality. Second, we schematize the values – instrumental, positional, intrinsic – of higher education that influenced well-being in the Soviet Union and Russia. We argue that the provision of higher education in these two state regimes complies with the political economy of two welfare models, suggesting a continuity across socialist and corporatist traditions. In the USSR, higher education was a part of a hybrid comprehensive-corporatist welfare model. Formally a universal right, it can be conceptualized as a state asset and a privilege attached to the class, entailing high intrinsic value. Higher education provision in Russia aligns with the conservative pattern while preserving traits of the socialist past and liberal transition. State commitment in the provision of public higher education and moderate marketization frame the hybrid nature of higher education as a social right and commodity with high instrumental and positional values.

Sources and transport of dissolved Mn, Fe, Cu, and Co in a semi-enclosed bay (Ariake Sea) in Japan

This study investigates the origins and transport mechanism of dissolved trace metals (d-Mn, d-Fe, d-Cu, and d-Co) and macronutrients in Ariake Sea, a shallow and semi-enclosed inlet bay during early summer. Concentrations of macronutrients and dissolved trace metals (d-Mn, d-Fe, d-Cu, and d-Co) were the highest in the surface waters of the innermost station in Ariake Sea and decreased gradually from the nearshore regions to the East China Sea. During estuarine mixing, d-Fe, d-Mn, and d-Cu showed non-conservative patterns, while d-Co exhibited a conservative pattern. This variability reflects the combined effects of water circulation and geochemically driven cycles in shaping the distribution of the metals. D-Mn and d-Fe were removed during estuarine mixing. Meanwhile, d-Cu pattern indicated input via intra-estuarine processes. The internal flux of d-Cu (1.6 × 1013 nmol/month) calculated from our data was slightly higher than its river fluxes (1.1 × 1013 nmol/month). We proposed sedimentary fluxes (2.1 × 1011–1.8 × 1013 nmol/month) supplied more d-Cu than other possible sources such as photodissolution of SPM, groundwater discharge, and atmospheric deposition. The conservative pattern of d-Co reflected a balance between input and removal during estuarine mixing.

Influence of Flue Gas Pattern Flow in Boiler Radiant Section on Heat Transfer

Abstract During the sizing of the radiant zone in boilers and furnaces, the most often used method is the Lobo-Evans model. This method is based on the perfect mixing model for flue gas flow inside the fire box, which represents a conservative or pessimistic flow pattern. This paper presents a different, optimistic model which is based on the plug flow for flue gas flow which results in the largest possible heat duty. The proposed model is given in two distinct forms—integral and numerical. As shown in the paper, the integral model results in small deviations with respect to the numerical model and, as such, is well suited for the engineering practice. Paper also presents an engineering approach to the calculation of the conductive heat transfer through the membrane wall, which is shown to be sufficiently accurate and simple for engineering calculations.

Tax Aggressiveness as a determining factor of Accounting Conservatism in Brazil

This paper investigates whether the degree of tax aggressiveness is a determinant of accounting conservatism. The taxable income has a dependent relationship with the accounting income in the Brazilian corporate income tax system. One way to reduce the corporate tax base is to adopt conservative accounting choices. After a conceptual discussion of accounting conservatism, differentiating conditional and unconditional conservativeness, and a thorough literature review on accounting conservatism by Brazilian academia. A literature gap was found since the relationship between a company's degree of tax aggressiveness, and its accounting conservatism behavior has not been investigated. For this research purpose, the Basu model was adopted, adapted with tax aggressiveness controls. The study period was from 2010 to 2019 for Brazilian firms from B3. The findings show a significant relationship between tax avoidance and conditional accounting conservatism. That is, more tax-aggressive firms tend to use more conservative accounting. The results provide insights that firms with higher effective tax rates are less inclined to use conservatism. The choice of a conservative accounting pattern may be in part to avoid the tax burden; therefore, this outcome states evidence that there is a difference between the degree of conservatism depending on the firm's tax aggressiveness profile.

Chromosome-level genome assembly and manually-curated proteome of model necrotroph Parastagonospora nodorum Sn15 reveals a genome-wide trove of candidate effector homologs, and redundancy of virulence-related functions within an accessory chromosome

BackgroundThe fungus Parastagonospora nodorum causes septoria nodorum blotch (SNB) of wheat (Triticum aestivum) and is a model species for necrotrophic plant pathogens. The genome assembly of reference isolate Sn15 was first reported in 2007. P. nodorum infection is promoted by its production of proteinaceous necrotrophic effectors, three of which are characterised – ToxA, Tox1 and Tox3.ResultsA chromosome-scale genome assembly of P. nodorum Australian reference isolate Sn15, which combined long read sequencing, optical mapping and manual curation, produced 23 chromosomes with 21 chromosomes possessing both telomeres. New transcriptome data were combined with fungal-specific gene prediction techniques and manual curation to produce a high-quality predicted gene annotation dataset, which comprises 13,869 high confidence genes, and an additional 2534 lower confidence genes retained to assist pathogenicity effector discovery. Comparison to a panel of 31 internationally-sourced isolates identified multiple hotspots within the Sn15 genome for mutation or presence-absence variation, which was used to enhance subsequent effector prediction. Effector prediction resulted in 257 candidates, of which 98 higher-ranked candidates were selected for in-depth analysis and revealed a wealth of functions related to pathogenicity. Additionally, 11 out of the 98 candidates also exhibited orthology conservation patterns that suggested lateral gene transfer with other cereal-pathogenic fungal species. Analysis of the pan-genome indicated the smallest chromosome of 0.4 Mbp length to be an accessory chromosome (AC23). AC23 was notably absent from an avirulent isolate and is predominated by mutation hotspots with an increase in non-synonymous mutations relative to other chromosomes. Surprisingly, AC23 was deficient in effector candidates, but contained several predicted genes with redundant pathogenicity-related functions.ConclusionsWe present an updated series of genomic resources for P. nodorum Sn15 – an important reference isolate and model necrotroph – with a comprehensive survey of its predicted pathogenicity content.

On the effect of phylogenetic correlations in coevolution-based contact prediction in proteins.

Coevolution-based contact prediction, either directly by coevolutionary couplings resulting from global statistical sequence models or using structural supervision and deep learning, has found widespread application in protein-structure prediction from sequence. However, one of the basic assumptions in global statistical modeling is that sequences form an at least approximately independent sample of an unknown probability distribution, which is to be learned from data. In the case of protein families, this assumption is obviously violated by phylogenetic relations between protein sequences. It has turned out to be notoriously difficult to take phylogenetic correlations into account in coevolutionary model learning. Here, we propose a complementary approach: we develop strategies to randomize or resample sequence data, such that conservation patterns and phylogenetic relations are preserved, while intrinsic (i.e. structure- or function-based) coevolutionary couplings are removed. A comparison between the results of Direct Coupling Analysis applied to real and to resampled data shows that the largest coevolutionary couplings, i.e. those used for contact prediction, are only weakly influenced by phylogeny. However, the phylogeny-induced spurious couplings in the resampled data are compatible in size with the first false-positive contact predictions from real data. Dissecting functional from phylogeny-induced couplings might therefore extend accurate contact predictions to the range of intermediate-size couplings.

A comprehensive characterization of novel CYP-BM3 homolog (CYP-BA) from Bacillus aryabhattai

Functionalizing C-H bond poses one of the most significant challenges for chemists providing them with very few substrate-specific synthetic routes. Despite being incredibly plastic in their enzymatic ability, they are confined with deficient enzymatic action and limited explicitness of the substrates. In this study, we have endeavored to characterize novel cytochrome P450 from Bacillus aryabhattai (CYP-BA), a homolog of CYP P450-BM3, by taking interdisciplinary approaches. We conducted structure and sequence comparison to understand the conservation pattern for active site residues, conserved fold, evolutionary relationships among others. Molecular dynamics simulations were performed to understand the dynamic nature and interaction with the substrates. CYP-BA was successfully cloned, purified, and characterized. The enzyme's stability toward various physicochemical parameters was evaluated by UV–vis spectroscopy and Circular Dichroism (CD) spectroscopy. Various saturated fatty acids being the natural cytochrome P450 substrates were evaluated as catalytic efficiency of substrate oxidation by CYP-BA. The binding affinity of these natural substrates was monitored against CYP-BA by isothermal titration calorimetry (ITC). The catalytic performance of CYP-BA was satisfactory enough to proceed to the next step, that is, engineering to expand the substrate range to include polycyclic aromatic hydrocarbons (PAH). This is the first evidence of cloning, purifying and characterizing a novel homolog of CYP-BM3 to enable a better understanding of this novel biocatalyst and to provide a platform toward expanding its catalytic process through enzyme engineering.

Understanding the molecular evolution of tiger diversity through DNA barcoding marker ND4 and NADH dehydrogenase complex using computational biology.

Currently, Tigers (the top predator of an ecosystem) are on the list of endangered species. Thus the need is to understand the tiger's population genomics to design their conservation strategies. We analyzed the molecular evolution of tiger diversity using NADH dehydrogenase subunit 4 (ND4), a significant electron transport chain component. We have analyzed nucleotide composition and distribution pattern of ND genes, molecular evolution, evolutionary conservation pattern and conserved blocks of NADH, phylogenomics of ND4, and estimating species divergence, etc., using different bioinformatics tools and software, and MATLAB programming and computing environment. The nucleotide composition and distribution pattern of ND genes in the tiger genome demonstrated an increase in the number of adenine (A) and a lower trend of A+T content in some place of the distribution analysis. However, the observed distributions were not significant (P > 0.05). Evolutionary conservation analysis showed three highly align blocks (186 to 198, 406 to 416, and 527 to 545). On mapping the molecular evolution of ND4 among model species (n = 30), we observed its presence in a broader range of species. ND4 based molecular evolution of tiger diversity and time divergence for a tiger (20 different other species) shows that genus Panthera originated more or less at a similar time. The nucleotide composition and nucleotide distribution pattern of tiger ND genes showed the evolutionary pattern and origin of tiger and Panthera lineage concerning the molecular clock, which will help to understand their adaptive evolution.

Quantifying the Evolutionary Constraints and Potential of Hepatitis C Virus NS5A Protein.

ABSTRACTRNA viruses, such as hepatitis C virus (HCV), influenza virus, and SARS-CoV-2, are notorious for their ability to evolve rapidly under selection in novel environments. It is known that the high mutation rate of RNA viruses can generate huge genetic diversity to facilitate viral adaptation. However, less attention has been paid to the underlying fitness landscape that represents the selection forces on viral genomes, especially under different selection conditions. Here, we systematically quantified the distribution of fitness effects of about 1,600 single amino acid substitutions in the drug-targeted region of NS5A protein of HCV. We found that the majority of nonsynonymous substitutions incur large fitness costs, suggesting that NS5A protein is highly optimized. The replication fitness of viruses is correlated with the pattern of sequence conservation in nature, and viral evolution is constrained by the need to maintain protein stability. We characterized the adaptive potential of HCV by subjecting the mutant viruses to selection by the antiviral drug daclatasvir at multiple concentrations. Both the relative fitness values and the number of beneficial mutations were found to increase with the increasing concentrations of daclatasvir. The changes in the spectrum of beneficial mutations in NS5A protein can be explained by a pharmacodynamics model describing viral fitness as a function of drug concentration. Overall, our results show that the distribution of fitness effects of mutations is modulated by both the constraints on the biophysical properties of proteins (i.e., selection pressure for protein stability) and the level of environmental stress (i.e., selection pressure for drug resistance).IMPORTANCE Many viruses adapt rapidly to novel selection pressures, such as antiviral drugs. Understanding how pathogens evolve under drug selection is critical for the success of antiviral therapy against human pathogens. By combining deep sequencing with selection experiments in cell culture, we have quantified the distribution of fitness effects of mutations in hepatitis C virus (HCV) NS5A protein. Our results indicate that the majority of single amino acid substitutions in NS5A protein incur large fitness costs. Simulation of protein stability suggests viral evolution is constrained by the need to maintain protein stability. By subjecting the mutant viruses to selection under an antiviral drug, we find that the adaptive potential of viral proteins in a novel environment is modulated by the level of environmental stress, which can be explained by a pharmacodynamics model. Our comprehensive characterization of the fitness landscapes of NS5A can potentially guide the design of effective strategies to limit viral evolution.

Three dimensional analysis of ontogenetic variation in fossil globorotaliiform planktic foraminiferal tests and its implications for ecology, life processes and functional morphology

Ontogenic trajectories recorded within the fossilized calcite tests of planktic foraminifera are significant for understanding their paleoecology and evolution. High-resolution 3-D imaging techniques enable quantitative measurement of test calcite and enclosed cavity volumes allowing a detailed characterization of the ontogenetic variations in the biomass to calcite ratio. Here we used micro-CT scanning to inspect ontogenetic variations among four globorotaliform planktic foraminiferal morphospecies from the late Miocene of International Ocean Discovery Program Site U1490 in the tropical Western Pacific. A conservative log-linear growth pattern is observed for all specimens. The proloculus size has an important control on the growth trajectory of the inspected specimens, and specimens with smaller proloculus volume generally have more chambers at the end of their life. The overall pattern of deviations from the log-linear growth trajectory among inspected specimens is well constrained, which varies between different groups in magnitude. The ontogenetic mean density, which is proposed here as an indicator of the degree of difficulty in producing positive buoyancy, shows a generally decreasing trend before the terminal stage in all specimens. We propose that the decreasing mean density (MD) as the test enlarges is an important adaption for planktic foraminifera to maintain an optimal habitat for nutrition and reproduction. The value of the mean density at the two-chambered stage exhibits a linear relationship with chamber volumes among inspected specimens with different habitats and different coiling forms, for which the ecological implications are explored.