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The mutualism between the giant tubeworm Riftia pachyptila and its endosymbiont Candidatus Endoriftia persephone has been extensively researched over the past 40 years. However, the lack of the host whole-genome information has impeded the full comprehension of the genotype/phenotype interface in Riftia. Here, we described the high-quality draft genome of Riftia , its complete mitogenome, and tissue-specific transcriptomic data. The Riftia genome presents signs of reductive evolution, with gene family contractions exceeding expansions. Expanded gene families are related to sulfur metabolism, detoxification, antioxidative stress, oxygen transport, immune system, and lysosomal digestion, reflecting evolutionary adaptations to the vent environment and endosymbiosis. Despite the derived body plan, the developmental gene repertoire in the gutless tubeworm is extremely conserved with the presence of a near intact and complete Hox cluster. Gene expression analyses establish that the trophosome is a multifunctional organ marked by intracellular digestion of endosymbionts, storage of excretory products, and hematopoietic functions. Overall, the plume and gonad tissues both in contact to the environment harbor highly expressed genes involved with cell cycle, programed cell death, and immunity indicating a high cell turnover and defense mechanisms against pathogens. We posit that the innate immune system plays a more prominent role into the establishment of the symbiosis during the infection in the larval stage, rather than maintaining the symbiostasis in the trophosome. This genome bridges four decades of physiological research in Riftia , whereas it simultaneously provides new insights into the development, whole organism functions, and evolution in the giant tubeworm. [ABSTRACT FROM AUTHOR]

In order to gain an evolutionary perspective on host-parasite-microbe interactions, evolutionary studies encompassing microbes across host and parasite species are necessary to identify patterns of cospeciation and speciation following host shifts. With appropriate experimental systems, geographic variations affecting the role of microbes in host-parasite interactions can be assessed by using a complete cross-experimental design, in which hosts from different localities are infected with parasites from their corresponding localities in the presence of either microbes isolated from the same localities or microbes from different test localities. Finally, when possible, experimental evolution of parasites and hosts in the presence or absence of the identified microbes can been used to test the effect of specific microbes on the evolution of the system and to identify mechanisms involved in parasite-microbe interaction. Phase one will compile information on previously characterized parasite-associated microbes and parasite-microbe interactions (already partially reviewed in [[15]-[16], [53]]), mine genomic and transcriptomic databases to detect microbial sequences, and characterize the complete microbiome of a set of parasites representing diverse taxa and environments. [Extracted from the article]

Non-uniform rates of morphological evolution and evolutionary increases in organismal complexity, captured in metaphors like “adaptive zones”, “punctuated equilibrium” and “blunderbuss patterns”, require more elaborate explanations than a simple gradual accumulation of mutations. Here we argue that non-uniform evolutionary increases in phenotypic complexity can be caused by a threshold-like response to growing ecological pressures resulting from evolutionary diversification at a given level of complexity. Acquisition of a new phenotypic feature allows an evolving species to escape this pressure but can typically be expected to carry significant physiological costs. Therefore, the ecological pressure should exceed a certain level to make such an acquisition evolutionarily successful. We present a detailed quantitative description of this process using a microevolutionary competition model as an example. The model exhibits sequential increases in phenotypic complexity driven by diversification at existing levels of complexity and a resulting increase in competitive pressure, which can push an evolving species over the barrier of physiological costs of new phenotypic features. [ABSTRACT FROM AUTHOR]

Mutualisms may be “key innovations” that spur lineage diversification by augmenting niche breadth, geographic range, or population size, thereby increasing speciation rates or decreasing extinction rates. Whether mutualism accelerates diversification in both interacting lineages is an open question. Research suggests that plants that attract ant mutualists have higher diversification rates than non-ant associated lineages. We ask whether the reciprocal is true: does the interaction between ants and plants also accelerate diversification in ants, i.e. do ants and plants cooperate-and-radiate? We used a novel text-mining approach to determine which ant species associate with plants in defensive or seed dispersal mutualisms. We investigated patterns of lineage diversification across a recent ant phylogeny using BiSSE, BAMM, and HiSSE models. Ants that associate mutualistically with plants had elevated diversification rates compared to non-mutualistic ants in the BiSSE model, with a similar trend in BAMM, suggesting ants and plants cooperate-and-radiate. However, the best-fitting model was a HiSSE model with a hidden state, meaning that diversification models that do not account for unmeasured traits are inappropriate to assess the relationship between mutualism and ant diversification. Against a backdrop of diversification rate heterogeneity, the best-fitting HiSSE model found that mutualism actually decreases diversification: mutualism evolved much more frequently in rapidly diversifying ant lineages, but then subsequently slowed diversification. Thus, it appears that ant lineages first radiated, then cooperated with plants. [ABSTRACT FROM AUTHOR]

Exploration and exploitation are contradictory in differential evolution (DE) algorithm. In order to balance the search behavior between exploitation and exploration better, a novel self-adaptive dual-strategy differential evolution algorithm (SaDSDE) is proposed. Firstly, a dual-strategy mutation operator is presented based on the “DE/best/2” mutation operator with better global exploration ability and “DE/rand/2” mutation operator with stronger local exploitation ability. Secondly, the scaling factor self-adaption strategy is proposed in an individual-dependent and fitness-dependent way without extra parameters. Thirdly, the exploration ability control factor is introduced to adjust the global exploration ability dynamically in the evolution process. In order to verify and analyze the performance of SaDSDE, we compare SaDSDE with 7 state-of-art DE variants and 3 non-DE based algorithms by using 30 Benchmark test functions of 30-dimensions and 100-dimensions, respectively. The experiments results demonstrate that SaDSDE could improve global optimization performance remarkably. Moreover, the performance superiority of SaDSDE becomes more significant with the increase of the problems’ dimension. [ABSTRACT FROM AUTHOR]

Evolving systems, be it an antibody repertoire in the face of mutating pathogens or a microbial population exposed to varied antibiotics, constantly search for adaptive solutions in time-varying fitness landscapes. Generalists refer to genotypes that remain fit across diverse selective pressures; while multi-drug resistant microbes are undesired yet prevalent, broadly-neutralizing antibodies are much wanted but rare. However, little is known about under what conditions such generalists with a high capacity to adapt can be efficiently discovered by evolution. In addition, can epistasis—the source of landscape ruggedness and path constraints—play a different role, if the environment varies in a non-random way? We present a generative model to estimate the propensity of evolving generalists in rugged landscapes that are tunably related and alternating relatively slowly. We find that environmental cycling can substantially facilitate the search for fit generalists by dynamically enlarging their effective basins of attraction. Importantly, these high performers are most likely to emerge at intermediate levels of ruggedness and environmental relatedness. Our approach allows one to estimate correlations across environments from the topography of experimental fitness landscapes. Our work provides a conceptual framework to study evolution in time-correlated complex environments, and offers statistical understanding that suggests general strategies for eliciting broadly neutralizing antibodies or preventing microbes from evolving multi-drug resistance. [ABSTRACT FROM AUTHOR]

Antagonistic interactions drive host–virus evolutionary arms races, which often manifest as recurrent amino acid changes (i.e., positive selection) at their protein–protein interaction interfaces. Here, we investigated whether combinatorial mutagenesis of positions under positive selection in a host antiviral protein could enhance its restrictive properties. We tested approximately 700 variants of human MxA, generated by combinatorial mutagenesis, for their ability to restrict Thogotovirus (THOV). We identified MxA super-restrictors with increased binding to the THOV nucleoprotein (NP) target protein and 10-fold higher anti-THOV restriction relative to wild-type human MxA, the most potent naturally occurring anti-THOV restrictor identified. Our findings reveal a means to elicit super-restrictor antiviral proteins by leveraging signatures of positive selection. Although some MxA super-restrictors of THOV were impaired in their restriction of H5N1 influenza A virus (IAV), other super-restrictor variants increased THOV restriction without impairment of IAV restriction. Thus, broadly acting antiviral proteins such as MxA mitigate breadth-versus-specificity trade-offs that could otherwise constrain their adaptive landscape. [ABSTRACT FROM AUTHOR]

Auxin is a major developmental regulator in plants and the acquisition of a transcriptional response to auxin likely contributed to developmental innovations at the time of water-to-land transition. Auxin Response Factors (ARFs) Transcription Factors (TFs) that mediate auxin-dependent transcriptional changes are divided into A, B and C evolutive classes in land plants. The origin and nature of the first ARF proteins in algae is still debated. Here, we identify the most ‘ancient’ ARF homologue to date in the early divergent charophyte algae Chlorokybus atmophyticus, CaARF. Structural modelling combined with biochemical studies showed that CaARF already shares many features with modern ARFs: it is capable of oligomerization, interacts with the TOPLESS co-repressor and specifically binds Auxin Response Elements as dimer. In addition, CaARF possesses a DNA-binding specificity that differs from class A and B ARFs and that was maintained in class C ARF along plants evolution. Phylogenetic evidence together with CaARF biochemical properties indicate that the different classes of ARFs likely arose from an ancestral proto-ARF protein with class C-like features. The foundation of auxin signalling would have thus happened from a pre-existing hormone-independent transcriptional regulation together with the emergence of a functional hormone perception complex. [ABSTRACT FROM AUTHOR]

Neuropeptides are a class of bioactive peptides shown to be involved in various physiological processes, including metabolism, development, and reproduction. Although neuropeptide candidates have been predicted from genomic and transcriptomic data, comprehensive characterization of neuropeptide repertoires remains a challenge owing to their small size and variable sequences. De novo prediction of neuropeptides from genome or transcriptome data is difficult and usually only efficient for those peptides that have identified orthologs in other animal species. Recent peptidomics technology has enabled systematic structural identification of neuropeptides by using the combination of liquid chromatography and tandem mass spectrometry. However, reliable identification of naturally occurring peptides using a conventional tandem mass spectrometry approach, scanning spectra against a protein database, remains difficult because a large search space must be scanned due to the absence of a cleavage enzyme specification. We developed a pipeline consisting of in silico prediction of candidate neuropeptides followed by peptide-spectrum matching. This approach enables highly sensitive and reliable neuropeptide identification, as the search space for peptide-spectrum matching is highly reduced. Nematostella vectensis is a basal eumetazoan with one of the most ancient nervous systems. We scanned the Nematostella protein database for sequences displaying structural hallmarks typical of eumetazoan neuropeptide precursors, including amino- and carboxyterminal motifs and associated modifications. Peptide-spectrum matching was performed against a dataset of peptides that are cleaved in silico from these putative peptide precursors. The dozens of newly identified neuropeptides display structural similarities to bilaterian neuropeptides including tachykinin, myoinhibitory peptide, and neuromedin-U/pyrokinin, suggesting these neuropeptides occurred in the eumetazoan ancestor of all animal species. [ABSTRACT FROM AUTHOR]

Cooperation is ubiquitous across all levels of biological systems ranging from microbial communities to human societies. It, however, seemingly contradicts the evolutionary theory, since cooperators are exploited by free-riders and thus are disfavored by natural selection. Many studies based on evolutionary game theory have tried to solve the puzzle and figure out the reason why cooperation exists and how it emerges. Network reciprocity is one of the mechanisms to promote cooperation, where nodes refer to individuals and links refer to social relationships. The spatial arrangement of mutant individuals, which refers to the clustering of mutants, plays a key role in network reciprocity. Besides, many other mechanisms supporting cooperation suggest that the clustering of mutants plays an important role in the expansion of mutants. However, the clustering of mutants and the game dynamics are typically coupled. It is still unclear how the clustering of mutants alone alters the evolutionary dynamics. To this end, we employ a minimal model with frequency independent fitness on a circle. It disentangles the clustering of mutants from game dynamics. The distance between two mutants on the circle is adopted as a natural indicator for the clustering of mutants or assortment. We find that the assortment is an amplifier of the selection for the connected mutants compared with the separated ones. Nevertheless, as mutants are separated, the more dispersed mutants are, the greater the chance of invasion is. It gives rise to the non-monotonic effect of clustering, which is counterintuitive. On the other hand, we find that less assortative mutants speed up fixation. Our model shows that the clustering of mutants plays a non-trivial role in fixation, which has emerged even if the game interaction is absent. [ABSTRACT FROM AUTHOR]

Highly pathogenic avian influenza (HPAI) virus subtype H7N3 has been circulating in poultry in Mexico since 2012 and vaccination has been used to control the disease. In this study, eight Mexican H7N3 HPAI viruses from 2015–2017 were isolated and fully sequenced. No evidence of reassortment was detected with other avian influenza (AI) viruses, but phylogenetic analyses show divergence of all eight gene segments into three genetic clusters by 2015, with 94.94 to 98.78 percent nucleotide homology of the HA genes when compared to the index virus from 2012. The HA protein of viruses from each cluster showed a different number of basic amino acids (n = 5–7) in the cleavage site, and six different patterns at the predicted N-glycosylation sites. Comparison of the sequences of the Mexican lineage H7N3 HPAI viruses and American ancestral wild bird AI viruses to characterize the virus evolutionary dynamics showed that the nucleotide substitution rates in PB2, PB1, PA, HA, NP, and NS genes greatly increased once the virus was introduced into poultry. The global nonsynonymous and synonymous ratios imply strong purifying selection driving the evolution of the virus. Forty-nine positively selected sites out of 171 nonsynonymous mutations were identified in the Mexican H7N3 HPAI viruses, including 7 amino acid changes observed in higher proportion in North American poultry origin AI viruses isolates than in wild bird-origin viruses. Continuous monitoring and molecular characterization of the H7N3 HPAI virus is important for better understanding of the virus evolutionary dynamics and further improving control measures including vaccination. [ABSTRACT FROM AUTHOR]

Previously we have described the V2-directed CAP256-VRC26 lineage that includes broadly neutralizing antibodies (bNAbs) that neutralize globally diverse strains of HIV. We also identified highly mutated “off-track” lineage members that share high sequence identity to broad members but lack breadth. Here, we defined the mutations that limit the breadth of these antibodies and the probability of their emergence. Mutants and chimeras between two pairs of closely related antibodies were generated: CAP256.04 and CAP256.25 (30% and 63% breadth, respectively) and CAP256.20 and CAP256.27 (2% and 59% breadth). Antibodies were tested against 14 heterologous HIV-1 viruses and select mutants to assess breadth and epitope specificity. A single R100rA mutation in the third heavy chain complementarity-determining region (CDRH3) introduced breadth into CAP256.04, but all three CAP256.25 heavy chain CDRs were required for potency. In contrast, in the CAP256.20/27 chimeras, replacing only the CDRH3 of CAP256.20 with that of CAP256.27 completely recapitulated breadth and potency, likely through the introduction of three charge-reducing mutations. In this individual, the mutations that limited the breadth of the off-track antibodies were predicted to occur with higher a probability than those in the naturally paired bNAbs, suggesting a low barrier to the evolution of the off-track phenotype. Mapping studies to determine the viral immunotypes (or epitope variants) that selected off-track antibodies indicated that unlike broader lineage members, CAP256.20 preferentially neutralized viruses containing 169Q. This suggests that this globally rare immunotype, which was common in donor CAP256, drove the off-track phenotype. These data show that affinity maturation to counter globally rare viral immunotypes can drive antibodies within a broad lineage along multiple pathways towards strain-specificity. Defining developmental pathways towards and away from breadth may facilitate the selection of immunogens that elicit bNAbs and minimize off-track antibodies. [ABSTRACT FROM AUTHOR]

The production of anticompetitor toxins is widespread among bacteria. Because production of such toxins is costly, it is typically regulated. In particular, many toxins are produced only when the local cell density is high. It is unclear which selection pressures shaped the evolution of density-dependent regulation of toxin production. Here, we study the evolution of toxin production, resistance and the response to a cell-density cue in a model of an evolving bacterial population with spatial structure. We present results for two growth regimes: (i) an undisturbed, fixed habitat in which only small fluctuations of cell density occur, and (ii) a serial-transfer regime with large fluctuations in cell density. We find that density-dependent toxin production can evolve under both regimes. However, the selection pressures driving the evolution of regulation differ. In the fixed habitat, regulation evolves because it allows cells to produce toxin only when opportunities for reproduction are highly limited (because of a high local cell density), and the effective fitness costs of toxin production are hence low. Under serial transfers, regulation evolves because it allows cells to switch from a fast-growing non-toxic phenotype when colonising a new habitat, to a slower-growing competitive toxic phenotype when the cell density increases. Colonies of such regulating cells rapidly expand into unoccupied space because their edges consist of fast-growing, non-toxin-producing cells, but are also combative because cells at the interfaces with competing colonies do produce toxin. Because under the two growth regimes different types of regulation evolve, our results underscore the importance of growth conditions in the evolution of social behaviour in bacteria. [ABSTRACT FROM AUTHOR]

The family of ribosomal proteins S1 contains about 20% of all bacterial proteins including the S1 domain. An important feature of this family is multiple copies of structural domains in bacteria, the number of which changes in a strictly limited range from one to six. In this study, the automated exhaustive analysis of 1453 sequences of S1 allowed us to demonstrate that the number of domains in S1 is a distinctive characteristic for phylogenetic bacterial grouping in main phyla. 1453 sequences of S1 were identified in 25 out of 30 different phyla according to the List of Prokaryotic Names with Standing in Nomenclature. About 62% of all records are identified as six-domain S1 proteins, which belong to phylum Proteobacteria. Four-domain S1 are identified mainly in proteins from phylum Firmicutes and Actinobacteria. Records belonging to these phyla are 33% of all records. The least represented two-domain S1 are about 0.6% of all records. The third and fourth domains for the most representative four- and six-domain S1 have the highest percentage of identity with the S1 domain from polynucleotide phosphorylase and S1 domains from one-domain S1. In addition, for these groups, the central part of S1 (the third domain) is more conserved than the terminal domains. [ABSTRACT FROM AUTHOR]

Humans depend on microbial communities for numerous ecosystem services such as global nutrient cycles, plant growth and their digestive health. Yet predicting dynamics and functioning of these complex systems is hard, making interventions to enhance functioning harder still. One simplifying approach is to assume that functioning can be predicted from the set of enzymes present in a community. Alternatively, ecological and evolutionary dynamics of species, which depend on how enzymes are packaged among species, might be vital for predicting community functioning. I investigate these alternatives by extending classical chemostat models of bacterial growth to multiple species that evolve in their use of chemical resources. Ecological interactions emerge from patterns of resource use, which change as species evolve in their allocation of metabolic enzymes. Measures of community functioning derive in turn from metabolite concentrations and bacterial density. Although the model shows considerable functional redundancy, species packaging does matter by introducing constraints on whether enzyme levels can reach optimum levels for the whole system. Evolution can either promote or reduce functioning compared to purely ecological models, depending on the shape of trade-offs in resource use. The model provides baseline theory for interpreting emerging data on evolution and functioning in real bacterial communities. [ABSTRACT FROM AUTHOR]

Mutational robustness quantifies the effect of random mutations on fitness. When mutational robustness is high, most mutations do not change fitness or have only a minor effect on it. From the point of view of fitness landscapes, robust genotypes form neutral networks of almost equal fitness. Using deterministic population models it has been shown that selection favors genotypes inside such networks, which results in increased mutational robustness. Here we demonstrate that this effect is massively enhanced by recombination. Our results are based on a detailed analysis of mesa-shaped fitness landscapes, where we derive precise expressions for the dependence of the robustness on the landscape parameters for recombining and non-recombining populations. In addition, we carry out numerical simulations on different types of random holey landscapes as well as on an empirical fitness landscape. We show that the mutational robustness of a genotype generally correlates with its recombination weight, a new measure that quantifies the likelihood for the genotype to arise from recombination. We argue that the favorable effect of recombination on mutational robustness is a highly universal feature that may have played an important role in the emergence and maintenance of mechanisms of genetic exchange. [ABSTRACT FROM AUTHOR]

Structural diversity in α-helical membrane proteins (MP) arises from variations in helix-helix crossings and contacts that may bias amino acid usage. Here, we reveal systematic changes in transmembrane amino acid frequencies (f) as a function of the number of helices (n). For eukarya, breaks in f(n) trends of packing (Ala, Gly and Pro), polar, and hydrophobic residues identify different MP assembly principles for 2≤n≤7, 8≤n≤12 and n≥13. In bacteria, the first f break already occurs after n = 6 in correlation to an earlier n peak in MP size distribution and dominance of packing over polar interactions. In contrast to the later n brackets, the integration levels of helix bundles continuously increased in the first, most populous brackets indicating the formation of single structural units (domains). The larger first bracket of eukarya relates to a balance of polar and packing interactions that enlarges helix-helix combinatorial possibilities (MP diversity). Between the evolutionary old, packing and new, polar residues f anti-correlations extend over all biological taxa, broadly ordering them according to evolutionary history and allowing f estimates for the earliest forms of life. Next to evolutionary history, the amino acid composition of MP is determined by size (n), proteome diversity, and effective amino acid cost. [ABSTRACT FROM AUTHOR]

Case studies of the evolution of molecular machines remain scarce. One of the most diverse and widespread homologous families of machines is the type IV filament (TFF) superfamily, comprised of type IV pili, type II secretion systems (T2SSs), archaella, and other less-well-characterized families. These families have functions including twitching motility, effector export, rotary propulsion, nutrient uptake, DNA uptake, and even electrical conductance, but it is unclear how such diversity evolved from a common ancestor. In this issue, Denise and colleagues take a significant step toward understanding evolution of the TFF superfamily by determining a global phylogeny and using it to infer an evolutionary pathway. Results reveal that the superfamily predates the divergence of Bacteria and Archaea, and show how duplications, acquisitions, and losses coincide with changes in function. Surprises include that tight adherence (Tad) pili were horizontally acquired from Archaea and that T2SSs were relatively recently repurposed from type IV pili. Results also enable better understanding of the function of the ATPase family that powers the superfamily. The study highlights the role of tinkering by exaptation—the repurposing of pre-existing functions for new roles—in the diversification of molecular machines. [ABSTRACT FROM AUTHOR]

Since 2013, epidemics caused by novel H7N9 avian influenza A viruses (AIVs) have become a considerable public health issue. This study investigated the evolution of these viruses at the population level. Compared to H7 and N9 before 2013, there were 18 and 24 substitutions in the majority of novel H7N9 AIVs, respectively. Nine of these in HA and six in NA were rare before 2013, and four of these in HA and two in NA displayed host tropism. S136(128)N and A143(135)V are located on the receptor binding sites of the HA1 subunit and might be important factors in determining the host species of novel H7N9 AIV. On an overall scale, the evolution of H7 and N9, both in terms of time distribution and host species, is under negative selection. However, both in HA and NA, several sites were under positive selection. In both the overall epidemics and the human-derived H7N9 AIVs, eight positive selection sites were identified in HA1, with some located within the known antigen epitopes or the receptor binding site(RBS) domain. This may induce variations in H7N9 AIV with positive selection. It is necessary to strengthen the surveillance of novel H7N9 AIVs, both in human and bird population to determine whether a new virus has emerged through selection pressure and to prevent future epidemics from occurring. [ABSTRACT FROM AUTHOR]

Hierarchical organisation is a prevalent feature of many complex networks appearing in nature and society. A relating interesting, yet less studied question is how does a hierarchical network evolve over time? Here we take a data driven approach and examine the time evolution of the network between the Medical Subject Headings (MeSH) provided by the National Center for Biotechnology Information (NCBI, part of the U. S. National Library of Medicine). The network between the MeSH terms is organised into 16 different, yearly updated hierarchies such as “Anatomy”, “Diseases”, “Chemicals and Drugs”, etc. The natural representation of these hierarchies is given by directed acyclic graphs, composed of links pointing from nodes higher in the hierarchy towards nodes in lower levels. Due to the yearly updates, the structure of these networks is subject to constant evolution: new MeSH terms can appear, terms becoming obsolete can be deleted or be merged with other terms, and also already existing parts of the network may be rewired. We examine various statistical properties of the time evolution, with a special focus on the attachment and detachment mechanisms of the links, and find a few general features that are characteristic for all MeSH hierarchies. According to the results, the hierarchies investigated display an interesting interplay between non-uniform preference with respect to multiple different topological and hierarchical properties. [ABSTRACT FROM AUTHOR]

In silico approaches have served a central role in the development of evolutionary theory for generations. This especially applies to the concept of the fitness landscape, one of the most important abstractions in evolutionary genetics, and one which has benefited from the presence of large empirical data sets only in the last decade or so. In this study, we propose a method that allows us to generate enormous data sets that walk the line between in silico and empirical: word usage frequencies as catalogued by the Google ngram corpora. These data can be codified or analogized in terms of a multidimensional empirical fitness landscape towards the examination of advanced concepts—adaptive landscape by environment interactions, clonal competition, higher-order epistasis and countless others. We argue that the greater Lexical Landscapes approach can serve as a platform that offers an astronomical number of fitness landscapes for exploration (at least) or theoretical formalism (potentially) in evolutionary biology. [ABSTRACT FROM AUTHOR]

Seemingly minor details of mathematical and computational models of evolution are known to change the effect of population structure on the outcome of evolutionary processes. For example, birth-death dynamics often result in amplification of selection, while death-birth processes have been associated with suppression. In many biological populations the interaction structure is not static. Instead, members of the population are in motion and can interact with different individuals at different times. In this work we study populations embedded in a flowing medium; the interaction network is then time dependent. We use computer simulations to investigate how this dynamic structure affects the success of invading mutants, and compare these effects for different coupled birth and death processes. Specifically, we show how the speed of the motion impacts the fixation probability of an invading mutant. Flows of different speeds interpolate between evolutionary dynamics on fixed heterogeneous graphs and well-stirred populations; this allows us to systematically compare against known results for static structured populations. We find that motion has an active role in amplifying or suppressing selection by fragmenting and reconnecting the interaction graph. While increasing flow speeds suppress selection for most evolutionary models, we identify characteristic responses to flow for the different update rules we test. In particular we find that selection can be maximally enhanced or suppressed at intermediate flow speeds. [ABSTRACT FROM AUTHOR]

NAD kinase (NADK) is the sole enzyme that phosphorylates nicotinamide adenine dinucleotide (NAD+/NADH) into NADP+/NADPH, which provides the chemical reducing power in anabolic (biosynthetic) pathways. While prokaryotes typically encode a single NADK, eukaryotes encode multiple NADKs. How these different NADK genes are all related to each other and those of prokaryotes is not known. Here we conduct phylogenetic analysis of NADK genes and identify major clade-defining patterns of NADK evolution. First, almost all eukaryotic NADK genes belong to one of two ancient eukaryotic sister clades corresponding to cytosolic (“cyto”) and mitochondrial (“mito”) clades. Secondly, we find that the cyto-clade NADK gene is duplicated in connection with loss of the mito-clade NADK gene in several eukaryotic clades or with acquisition of plastids in Archaeplastida. Thirdly, we find that horizontal gene transfers from proteobacteria have replaced mitochondrial NADK genes in only a few rare cases. Last, we find that the eukaryotic cyto and mito paralogs are unrelated to independent duplications that occurred in sporulating bacteria, once in mycelial Actinobacteria and once in aerobic endospore-forming Firmicutes. Altogether these findings show that the eukaryotic NADK gene repertoire is ancient and evolves episodically with major evolutionary transitions. [ABSTRACT FROM AUTHOR]

Dengue virus serotype 4 (DENV 4) has had a relatively low prevalence worldwide for decades; however, likely due to data paucity, no study has investigated the epidemiology and evolutionary dynamics of DENV 4 genotype I (DENV 4-I). This study aims to understand the diversity, epidemiology and dynamics of DENV 4-I. We collected 404 full length DENV4-1 envelope (E) gene sequences from 14 countries using two sources: Yunnan Province in China (15 strains during 2013–2016) and GenBank (489 strains up to 2018-01-11). Conducting phylogenetic and phylogeographical analyses, we estimated the virus spread, population dynamics, and selection pressures using different statistical analysis methods (substitution saturation, likelihood mapping, Bayesian coalescent inference, and maximum likelihood estimation). Our results show that during the last 60 years (1956–2016), DENV 4-I was present in mainland and maritime Southeast Asia, the Indian subcontinent, the southern provinces of China, parts of Brazil and Australia. The recent spread of DENV 4-I likely originated in the Philippines and later spread to Thailand. From Thailand, it spread to adjacent countries and eventually the Indian subcontinent. Apparently diverging around years 1957, 1963, 1976 and 1990, the different Clades (Clade I-V) were defined. The mean overall evolution rate of DENV 4-I was 9.74 (95% HPD: 8.68–10.82) × 10−4 nucleotide substitutions/site/year. The most recent common ancestor for DENV 4-I traces back to 1956. While the demographic history of DENV 4-I fluctuated, peaks appeared around 1982 and 2006. While purifying selection dominated the majority of E-gene evolution of DENV 4-I, positive selection characterized Clade III (Vietnam). DENV 4-I evolved in situ in Southeast Asia and the Indian subcontinent. Thailand and Indian acted as the main and secondary virus distribution hubs globally and regionally. Our phylogenetic analysis highlights the need for strengthened regional cooperation on surveillance and sharing of sample sequences to improve global dengue control and cross-border transmission prevention efforts. [ABSTRACT FROM AUTHOR]

Syntrophy allows a microbial community as a whole to survive in an environment, even though individual microbes cannot. The metabolic interdependence typical of syntrophy is thought to arise from the accumulation of degenerative mutations during the sustained co-evolution of initially self-sufficient organisms. An alternative and underexplored possibility is that syntrophy can emerge spontaneously in communities of organisms that did not co-evolve. Here, we study this de novo origin of syntrophy using experimentally validated computational techniques to predict an organism’s viability from its metabolic reactions. We show that pairs of metabolisms that are randomly sampled from a large space of possible metabolism and viable on specific primary carbon sources often become viable on new carbon sources by exchanging metabolites. The same biochemical reactions that are required for viability on primary carbon sources also confer viability on novel carbon sources. Our observations highlight a new and important avenue for the emergence of metabolic adaptations and novel ecological interactions. [ABSTRACT FROM AUTHOR]

Replicating recombinant vector vaccines consist of a fully competent viral vector backbone engineered to express an antigen from a foreign transgene. From the perspective of viral replication, the transgene is not only dispensable but may even be detrimental. Thus vaccine revertants that delete or inactivate the transgene may evolve to dominate the vaccine virus population both during the process of manufacture of the vaccine as well as during the course of host infection. A particular concern is that this vaccine evolution could reduce its antigenicity—the immunity elicited to the transgene. We use mathematical and computational models to study vaccine evolution and immunity. These models include evolution arising during the process of manufacture, the dynamics of vaccine and revertant growth, plus innate and adaptive immunity elicited during the course of infection. Although the selective basis of vaccine evolution is easy to comprehend, the immunological consequences are not. One complication is that the opportunity for vaccine evolution is limited by the short period of within-host growth before the viral population is cleared. Even less obvious, revertant growth may only weakly interfere with vaccine growth in the host and thus have a limited effect on immunity to vaccine. Overall, we find that within-host vaccine evolution can sometimes compromise vaccine immunity, but only when the extent of evolution during vaccine manufacture is severe, and this evolution can be easily avoided or mitigated. [ABSTRACT FROM AUTHOR]

Background: Long-term growth in HIV-infected infants treated early in resource-limited settings is poorly documented. Incidence of growth retardation, instantaneous risk of death related to malnutrition and growth parameters evolution during the first five years of life of uninfected and early treated HIV-infected children were compared and associated factors with growth retardation were identified. Methods: Weight-for-age (WAZ), weight-for-length (WLZ), and length-for-age (LAZ) Z-scores were calculated. The ANRS-PEDIACAM cohort includes four groups of infants with three enrolled during the first week of life: HIV-infected (HI, n = 69), HIV-exposed uninfected (HEU, n = 205) and HIV-unexposed uninfected (HUU, n = 196). The last group included HIV-infected infants diagnosed before 7 months of age (HIL, n = 141). The multi-state Markov model was used to describe the incidence of growth retardation and identified associated factors. Results: During the first 5 years, 27.5% of children experienced underweight (WAZ<-2), 60.4% stunting (LAZ<-2) and 41.1% wasting (WLZ<-2) at least once. The instantaneous risk of death observed from underweight state (35.3 [14.1–88.2], 84.0 [25.5–276.3], and 6.0 [1.5–24.1] per 1000 person-months for 0–6 months, 6–12 months, and 12–60 months respectively) was higher than from non-underweight state (9.6 [5.7–16.1], 20.1 [10.3–39.4] and 0.3 [0.1–0.9] per 1000 person-months). Compared to HEU, HIL and HI children were most at risk of wasting (adjusted HR (aHR) = 4.3 (95%CI: 1.9–9.8), P<0.001 and aHR = 3.3 (95%CI: 1.4–7.9), P = 0.01 respectively) and stunting for HIL (aHR = 8.4 (95%CI: 2.4–29.7). The risk of underweight was higher in HEU compared to HUU children (aHR = 5.0 (CI: 1.4–10.0), P = 0.001). Others associated factors to growth retardation were chronic pathologies, small size at birth, diarrhea and CD4< 25%. Conclusions: HIV-infected children remained at high risk of wasting and stunting within the first 5 years period of follow-up. There is a need of identifying suitable nutritional support and best ways to integrate it with cART in pediatric HIV infection global care. [ABSTRACT FROM AUTHOR]

Recent research in machine learning pointed to the core problem of state-of-the-art models which impedes their widespread adoption in different domains. The models’ inability to differentiate between noise and subtle, yet significant variation in data leads to their vulnerability to adversarial perturbations that cause wrong predictions with high confidence. The study is aimed at identifying whether the algorithms inspired by biological evolution may achieve better results in cases where brittle robustness properties are highly sensitive to the slight noise. To answer this question, we introduce the new robust gradient descent inspired by the stability and adaptability of biological systems to unknown and changing environments. The proposed optimization technique involves an open-ended adaptation process with regard to two hyperparameters inherited from the generalized Verhulst population growth equation. The hyperparameters increase robustness to adversarial noise by penalizing the degree to which hardly visible changes in gradients impact prediction. The empirical evidence on synthetic and experimental datasets confirmed the viability of the bio-inspired gradient descent and suggested promising directions for future research. The code used for computational experiments is provided in a repository at . [ABSTRACT FROM AUTHOR]

Mathematical models have been used successfully at diverse scales of biological organization, ranging from ecology and population dynamics to stochastic reaction events occurring between individual molecules in single cells. Generally, many biological processes unfold across multiple scales, with mutations being the best studied example of how stochasticity at the molecular scale can influence outcomes at the population scale. In many other contexts, however, an analogous link between micro- and macro-scale remains elusive, primarily due to the challenges involved in setting up and analyzing multi-scale models. Here, we employ such a model to investigate how stochasticity propagates from individual biochemical reaction events in the bacterial innate immune system to the ecology of bacteria and bacterial viruses. We show analytically how the dynamics of bacterial populations are shaped by the activities of immunity-conferring enzymes in single cells and how the ecological consequences imply optimal bacterial defense strategies against viruses. Our results suggest that bacterial populations in the presence of viruses can either optimize their initial growth rate or their population size, with the first strategy favoring simple immunity featuring a single restriction modification system and the second strategy favoring complex bacterial innate immunity featuring several simultaneously active restriction modification systems. [ABSTRACT FROM AUTHOR]

Avian influenza virus H9N2 has been endemic in birds in the Middle East, in particular in Egypt with multiple cases of human infections since 1998. Despite concerns about the pandemic threat posed by H9N2, little is known about the biological properties of H9N2 in this epicentre of infection. Here, we investigated the evolutionary dynamics of H9N2 in the Middle East and identified phylogeny-associated PB2 mutations that acted cooperatively to increase H9N2 replication/transcription in human cells. The accumulation of PB2 mutations also correlated with an increase in H9N2 virus growth in the upper and lower airways of mice and in virulence. These mutations clustered on a solvent-exposed region in the PB2-627 domain in proximity to potential interfaces with host factors. These PB2 mutations have been found at high prevalence during evolution of H9N2 in the field, indicating that they have provided a selective advantage for viral adaptation to infect poultry. Therefore, continuous prevalence of H9N2 virus in the Middle East has generated a far more fit or optimized replication phenotype, leading to an expanded viral host range, including to mammals, which may pose public health risks beyond the current outbreaks. [ABSTRACT FROM AUTHOR]

Protein kinases catalyse the phosphorylation of target proteins, controlling most cellular processes. The specificity of serine/threonine kinases is partly determined by interactions with a few residues near the phospho-acceptor residue, forming the so-called kinase-substrate motif. Kinases have been extensively duplicated throughout evolution, but little is known about when in time new target motifs have arisen. Here, we show that sequence variation occurring early in the evolution of kinases is dominated by changes in specificity-determining residues. We then analysed kinase specificity models, based on known target sites, observing that specificity has remained mostly unchanged for recent kinase duplications. Finally, analysis of phosphorylation data from a taxonomically broad set of 48 eukaryotic species indicates that most phosphorylation motifs are broadly distributed in eukaryotes but are not present in prokaryotes. Overall, our results suggest that the set of eukaryotes kinase motifs present today was acquired around the time of the eukaryotic last common ancestor and that early expansions of the protein kinase fold rapidly explored the space of possible target motifs. [ABSTRACT FROM AUTHOR]

The role of foot-and-mouth disease virus (FMDV) persistently infected ruminants in initiating new outbreaks remains controversial, and the perceived threat posed by such animals hinders international trade in FMD-endemic countries. In this study we report longitudinal analyses of genetic and antigenic variations of FMDV serotype O/ME-SA/Ind2001d sublineage during naturally occurring, persistent infection in cattle and buffalo at an organised dairy farm in India. The proportion of animals from which FMDV RNA was recovered was not significantly different between convalescent (post-clinical) and sub-clinically infected animals or between cattle and buffalo across the sampling period. However, infectious virus was isolated from a higher proportion of buffalo samples and for a longer duration compared to cattle. Analysis of the P1 sequences from recovered viruses indicated fixation of mutations at the rate of 1.816 x 10-2substitution/site/year (s/s/y) (95% CI 1.362–2.31 x 10−2 s/s/y). However, the majority of point mutations were transitional substitutions. Within individual animals, the mean dN/dS (ω) value for the P1 region varied from 0.076 to 0.357, suggesting the selection pressure acting on viral genomes differed substantially across individual animals. Statistical parsimony analysis indicated that all of the virus isolates from carrier animals originated from the outbreak virus. The antigenic relationship value as determined by 2D-VNT assay revealed fluctuation of antigenic variants within and between carrier animals during the carrier state which suggested that some carrier viruses had diverged substantially from the protection provided by the vaccine strain. This study contributes to understanding the extent of within-host and within-herd evolution that occurs during the carrier state of FMDV. [ABSTRACT FROM AUTHOR]

Classically, phenotype is what is observed, and genotype is the genetic makeup. Statistical studies aim to project phenotypic likelihoods of genotypic patterns. The traditional genotype-to-phenotype theory embraces the view that the encoded protein shape together with gene expression level largely determines the resulting phenotypic trait. Here, we point out that the molecular biology revolution at the turn of the century explained that the gene encodes not one but ensembles of conformations, which in turn spell all possible gene-associated phenotypes. The significance of a dynamic ensemble view is in understanding the linkage between genetic change and the gained observable physical or biochemical characteristics. Thus, despite the transformative shift in our understanding of the basis of protein structure and function, the literature still commonly relates to the classical genotype–phenotype paradigm. This is important because an ensemble view clarifies how even seemingly small genetic alterations can lead to pleiotropic traits in adaptive evolution and in disease, why cellular pathways can be modified in monogenic and polygenic traits, and how the environment may tweak protein function. [ABSTRACT FROM AUTHOR]

The development of high-throughput genome sequencing enables accurate measurements of levels of sub-consensus intra-host virus genetic diversity and analysis of the role played by natural selection during cross-species transmission. We analysed the natural and experimental evolution of rabies virus (RABV), an important example of a virus that is able to make multiple host jumps. In particular, we (i) analyzed RABV evolution during experimental host switching with the goal of identifying possible genetic markers of host adaptation, (ii) compared the mutational changes observed during passage with those observed in natura, and (iii) determined whether the colonization of new hosts or tissues requires adaptive evolution in the virus. To address these aims, animal infection models (dog and fox) and primary cell culture models (embryo brain cells of dog and fox) were developed and viral variation was studied in detail through deep genome sequencing. Our analysis revealed a strong unidirectional host evolutionary effect, as dog-adapted rabies virus was able to replicate in fox and fox cells relatively easily, while dogs or neuronal dog cells were not easily susceptible to fox adapted-RABV. This suggests that dog RABV may be able to adapt to some hosts more easily than other host variants, or that when RABV switched from dogs to red foxes it lost its ability to adapt easily to other species. Although no difference in patterns of mutation variation between different host organs was observed, mutations were common following both in vitro and in vivo passage. However, only a small number of these mutations also appeared in natura, suggesting that adaptation during successful cross-species virus transmission is a complex, multifactorial evolutionary process. [ABSTRACT FROM AUTHOR]

Behavioural innovation, the use of new behaviours or existing ones in novel contexts, can have important ecological and evolutionary consequences for animals. An understanding of these consequences would be incomplete without considering the traits that predispose certain individuals to exhibit innovative behaviour. Several individual and ecological variables are hypothesized to affect innovativeness, but empirical studies show mixed results. We examined the effects of dominance rank, exploratory personality, and urbanisation on the innovativeness of wild-caught black-capped chickadees using a survival analysis of their performance in two problem-solving tasks. Additionally, we provide one of the first investigations of the predictors of persistence in a problem-solving context. For lever pulling, we found a trend for dominants to outperform subordinates, particularly in rural birds, which did not align with predictions from the necessity drives innovation hypothesis. When examining possible explanations for this trend we found that older chickadees outperformed younger birds. This follow-up analysis also revealed a positive effect of exploratory personality on the lever-pulling performance of chickadees. Our results suggest that experience may foster innovation in certain circumstances, for instance via the application of previously-acquired information or skills to a novel problem. As we found different predictors for both tasks, this suggests that task characteristics influence the innovative propensity of individuals, and that their effects should be investigated experimentally. [ABSTRACT FROM AUTHOR]

The origin and subsequent maintenance of sex and recombination are among the most elusive and controversial problems in evolutionary biology. Here, we propose a novel hypothesis, suggesting that sexual reproduction not only evolved to reduce the negative effects of the accumulation of deleterious mutations and processes associated with pathogen and/or parasite resistance but also to prevent invasion by transmissible selfish neoplastic cheater cells, henceforth referred to as transmissible cancer cells. Sexual reproduction permits systematic change of the multicellular organism's genotype and hence an enhanced detection of transmissible cancer cells by immune system. Given the omnipresence of oncogenic processes in multicellular organisms, together with the fact that transmissible cancer cells can have dramatic effects on their host fitness, our scenario suggests that the benefits of sex and concomitant recombination will be large and permanent, explaining why sexual reproduction is, despite its costs, the dominant mode of reproduction among eukaryotes. [ABSTRACT FROM AUTHOR]

Recent increase in the detection of unusual G1P[8], G3P[8], G8P[8], and G9P[4] Rotavirus A (RVA) strains bearing the DS-1-like constellation of the non-G, non-P genes (hereafter referred to as the genotype 2 backbone) requires better understanding of their evolutionary relationship. However, within a genotype, there is lack of a consensus lineage designation framework and a set of common sequences that can serve as references. Phylogenetic analyses were carried out on over 8,500 RVA genotype 2 genes systematically retrieved from the rotavirus database within the NCBI Virus Variation Resource. In line with previous designations, using pairwise comparison of cogent nucleotide sequences and stringent bootstrap support, reference lineages were defined. This study proposes a lineage framework and provides a dataset ranging from 34 to 145 sequences for each genotype 2 gene for orderly lineage designation of global genotype 2 genes of RVAs detected in human and animals. The framework identified five to 31 lineages depending on the gene. The least number of lineages (five to seven) were observed in genotypes A2 (NSP1), T2 (NSP3) and H2 (NSP5) which are limited to human RVA whereas the most number of lineages (31) was observed in genotype E2 (NSP4). Sharing of the same lineage constellations of the genotype 2 backbone genes between recently-emerging, unusual G1P[8], G3P[8], G8P[8] and G9P[4] reassortants and many contemporary G2P[4] strains provided strong support to the hypothesis that unusual genotype 2 strains originated primarily from reassortment events in the recent past involving contemporary G2P[4] strains as one parent and ordinary genotype 1 strains or animal RVA strains as the other. The lineage framework with selected reference sequences will help researchers to identify the lineage to which a given genotype 2 strain belongs, and trace the evolutionary history of common and unusual genotype 2 strains in circulation. [ABSTRACT FROM AUTHOR]

Different genomic sites evolve inter-dependently due to the combined action of epistasis, defined as a non-multiplicative contribution of alleles at different loci to genome fitness, and the physical linkage of different loci in genome. Both epistasis and linkage, partially compensated by recombination, cause correlations between allele frequencies at the loci (linkage disequilibrium, LD). The interaction and competition between epistasis and linkage are not fully understood, nor is their relative sensitivity to recombination. Modeling an adapting population in the presence of random mutation, natural selection, pairwise epistasis, and random genetic drift, we compare the contributions of epistasis and linkage. For this end, we use a panel of haplotype-based measures of LD and their various combinations calculated for epistatic and non-epistatic pairs separately. We compute the optimal percentages of detected and false positive pairs in a one-time sample of a population of moderate size. We demonstrate that true interacting pairs can be told apart in a sufficiently short genome within a narrow window of time and parameters. Outside of this parameter region, unless the population is extremely large, shared ancestry of individual sequences generates pervasive stochastic LD for non-interacting pairs masking true epistatic associations. In the presence of sufficiently strong recombination, linkage effects decrease faster than those of epistasis, and the detection of epistasis improves. We demonstrate that the epistasis component of locus association can be isolated, at a single time point, by averaging haplotype frequencies over multiple independent populations. These results demonstrate the existence of fundamental restrictions on the protocols for detecting true interactions in DNA sequence sets. [ABSTRACT FROM AUTHOR]

Evolutionary innovations are qualitatively novel traits that emerge through evolution and increase biodiversity. The genetic mechanisms of innovation remain poorly understood. A systems view of innovation requires the analysis of genotype networks—the vast networks of genetic variants that produce the same phenotype. Innovations can occur at the intersection of two different genotype networks. However, the experimental characterization of genotype networks has been hindered by the vast number of genetic variants that need to be functionally analyzed. Here, we use high-throughput sequencing to study the fitness landscape at the intersection of the genotype networks of two catalytic RNA molecules (ribozymes). We determined the ability of numerous neighboring RNA sequences to catalyze two different chemical reactions, and we use these data as a proxy for a genotype to fitness map where two functions come in close proximity. We find extensive functional overlap, and numerous genotypes can catalyze both functions. We demonstrate through evolutionary simulations that these numerous points of intersection facilitate the discovery of a new function. However, the rate of adaptation of the new function depends upon the local ruggedness around the starting location in the genotype network. As a consequence, one direction of adaptation is more rapid than the other. We find that periods of neutral evolution increase rates of adaptation to the new function by allowing populations to spread out in their genotype network. Our study reveals the properties of a fitness landscape where genotype networks intersect and the consequences for evolutionary innovations. Our results suggest that historic innovations in natural systems may have been facilitated by overlapping genotype networks. [ABSTRACT FROM AUTHOR]

Evolution of complex multicellular life began from the emergence of a life cycle involving the formation of cell clusters. The opportunity for cells to interact within clusters provided them with an advantage over unicellular life forms. However, what kind of interactions may lead to the evolution of multicellular life cycles? Here, we combine evolutionary game theory with a model for the emergence of multicellular groups to investigate how cell interactions can influence reproduction modes during the early stages of the evolution of multicellularity. In our model, the presence of both cell types is maintained by stochastic phenotype switching during cell division. We identify evolutionary optimal life cycles as those which maximize the population growth rate. Among all interactions captured by two-player games, the vast majority promotes two classes of life cycles: (i) splitting into unicellular propagules or (ii) fragmentation into two offspring clusters of equal (or almost equal) size. Our findings indicate that the three most important characteristics, determining whether multicellular life cycles will evolve, are the average performance of homogeneous groups, heterogeneous groups, and solitary cells. [ABSTRACT FROM AUTHOR]

Background: To access the long term relationship between efavirenz plasma concentrations and evolution of HIV RNA loads and CD4 cell counts in children. Methods: Retrospective analysis of data from HIV-infected children on first line efavirenz-containing regimen. A population pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the evolution of HIV RNA load and CD4 cell count (efficacy outcomes) in relation to efavirenz plasma concentration. Individual CYP2B6 516 G>T genotype data were not available for this analysis. A score (ISEFV) quantifying the effect of efavirenz concentrations on the long-term HIV replication was calculated from efavirenz concentrations and PD parameters and, a value of ISEFV below which HIV replication is likely not suppressed was determined. Cox proportional hazards regression models were used to assess the association of the risk of viral replication with ISEFV, and with efavirenz mid-dose concentration(C12). Results: At treatment initiation, median (interquartile range, IQR) age was 8 years (5 to 10), body weight 17 kg (14 to 23), HIV RNA load 5.1 log10 copies/mL (4.6 to 5.4), and CD4 cell count 71 cells/mm3. A model of PK-PD viral dynamics assuming that efavirenz decreases the rate of infected host cells adequately described the relationship of interest. After adjusting for age, baseline HIV RNA load and CD4 cell counts an ISEFV <85% was significantly associated with a higher risk of viral replication (p-value <0.001) while no significant association was observed with C12 <1.0 mg/L. Conclusion: The ISEFV score was a good predictor of viral replication in children on efavirenz-based treatment. [ABSTRACT FROM AUTHOR]

Background: HCV genotype 6 (HCV-6) typically circulates in Southeast Asia and exhibits the highest genetic diversity among the eight HCV genotypes. In our previous work, a group of HCV-6 sequences was not clearly classified. Here, we further characterized this HCV-6 variant and analyzed the evolutionary history of the enlarged HCV-6 family. Methods: Blood samples from eight HCV seropositive samples collected from intravenous drug users (IDUs) in 2014 in Yunnan Province, China. The full-length HCV genome sequences were amplified by using reverse transcription PCR followed by DNA sequencing and phylogenetic analysis. Bayesian evolutionary analysis was performed with the complete coding region sequences of subtype 6a-6xh. Results: The eight genomes had the same coding region of 9051 nucleotides. The complete coding region sequences of the eight HCV isolates formed a distinct phylogenetic group from the previously assigned HCV-6 subtypes (6a-6xf), however which clustered with 6xg reference sequences that were found in Kachin State, Myanmar, and recently assigned and released. The p-distances of the eight isolates to subtype 6a-6xf and 6xh ranged from 0.143 to 0.283. Based on the HCV-6 complete coding region sequences, we constructed a timescaled phylogenetic tree to reveal the HCV-6 evolutionary history, in which there were four HCV-6 phylogenetic subsets, whose median tMRCAs were 294.8, 388.5, 348.5 and 197.0 years ago, respectively. Subtype 6xg clustered into Subset I, and had the most recent common ancestor with subtype 6n, which dated back to 101.2 (95% HPD: 78.7, 125.8) years ago. The genetic evolutionary analysis further confirmed that subtype 6xg originated from Myanmar, and transmitted to Dehong through cross-border IDUs. Conclusion: The HCV-6 variant characterized in this study belonged to newly assigned subtype 6xg. Our finding further confirmed the assignment of 6xg. HCV-6 family was highly divers and had a complicated evolutionary history in Southeast Asia. It is necessary to further characterize HCV-6 genetics in this region. [ABSTRACT FROM AUTHOR]

Selection pressures leading to extreme, female-biased sexual size dimorphism (SSD) in spiders continue to be debated. It has been proposed that males of sexually size dimorphic spiders could be small because gravity constrains adult agility (locomotor abilities). Accordingly, small males should achieve higher vertical climbing speeds and should be more prone to bridge. The curvilinear model of the gravity hypothesis predicts a negative relationship between vertical climbing speed and male body size only over a threshold of 7.6 mm, 42.5 mg. Because males of most species with extreme SSD fall well below this threshold, the relationship between male size and agility at this scale remains vague. Here, we tested three hypotheses on how male size, mass and age (after maturation) relate to vertical climbing and bridging ability in Nephilingis cruentata, a highly sexually dimorphic orb-weaver with males well below the size threshold. We placed males of different sizes and adult ages in a vertical platform and recorded their climbing speeds. Contrary to the original study testing male bridging ability as binary variable, we measured the duration of the crossing of the bridging thread, as well as its sagging distance. Male body size and mass positively related to the vertical climbing speed and to the distance of the sagging thread during bridging, but had no influence on the bridging duration. The detected positive correlation between male size/mass and vertical climbing speed goes against our first prediction, that small males would have vertical climbing advantage in Nephilingis cruentata, but agrees with the curvilinear model. Against our second prediction, small males were not faster during bridging. Finally, in agreement with our third prediction, threads sagged more in heavier males. These results suggest that small male size confers no agility advantages in Nephilingis cruentata. [ABSTRACT FROM AUTHOR]

Since 1959 with the proposal of Double Agar Layer (DAL) method for phage detection and quantification, many sophisticated methods have emerged meanwhile. However, many of them are either too complex/expensive or insensitive to replace routine utilization of DAL method in clinical, environmental and industrial environments. For that purpose, we have explored an alternative method for the detection and quantification of bacteriophages that fulfills the criteria of being rapid, simple and inexpensive. In this paper we have developed a method based on the analysis of optical density kinetics in bacterial cultures exposed to phage-containing samples. Although the decrease in optical density caused by cell lysis was one of the first observable consequences of the effect of viral infection in bacterial cultures, the potential of the method for the assessment of phage abundance has never been fully exploited. In this work we carry out a detailed study of optical density kinetics in phage-infected bacterial cultures, as a function of both, phage abundance and initial concentration of the host organisms. In total, 90 different combinations of bacteria/phage concentrations have been used. The data obtained provide valuable information about sensitivity ranges, duration of the assay, percentages of inhibition and type of lysing behavior for each phage concentration. The method described can detect, as few as 10 phage particles per assay volume after a phage incubation period of 3.5h. The duration of the assay can be shortened to 45min at the expense of losing sensitivity and increasing the limit of detection to 108 pfu/ml. Despite using non-sophisticated technology, the method described has shown sensitivity and response time comparable to other high-end methods. The simplicity of the technology and of the analytical steps involved, make the system susceptible of miniaturization and automation for high-throughput applications which can be implemented in routine analysis in many environments. [ABSTRACT FROM AUTHOR]

Mutations drive evolution and were assumed to occur by chance: constantly, gradually, roughly uniformly in genomes, and without regard to environmental inputs, but this view is being revised by discoveries of molecular mechanisms of mutation in bacteria, now translated across the tree of life. These mechanisms reveal a picture of highly regulated mutagenesis, up-regulated temporally by stress responses and activated when cells/organisms are maladapted to their environments—when stressed—potentially accelerating adaptation. Mutation is also nonrandom in genomic space, with multiple simultaneous mutations falling in local clusters, which may allow concerted evolution—the multiple changes needed to adapt protein functions and protein machines encoded by linked genes. Molecular mechanisms of stress-inducible mutation change ideas about evolution and suggest different ways to model and address cancer development, infectious disease, and evolution generally. [ABSTRACT FROM AUTHOR]

Knowledge of the within-host frequencies of resistance-associated amino acid variants (RAVs) is important to the identification of optimal drug combinations for the treatment of hepatitis C virus (HCV) infection. Multiple RAVs may exist in infected individuals, often below detection limits, at any resistance locus, defining the diversity of accessible resistance pathways. We developed a multiscale mathematical model to estimate the pre-treatment frequencies of the entire spectrum of mutants at chosen loci. Using a codon-level description of amino acids, we performed stochastic simulations of intracellular dynamics with every possible nucleotide variant as the infecting strain and estimated the relative infectivity of each variant and the resulting distribution of variants produced. We employed these quantities in a deterministic multi-strain model of extracellular dynamics and estimated mutant frequencies. Our predictions captured database frequencies of the RAV R155K, resistant to NS3/4A protease inhibitors, presenting a successful test of our formalism. We found that mutational pathway maps, interconnecting all viable mutants, and strong founder effects determined the mutant spectrum. The spectra were vastly different for HCV genotypes 1a and 1b, underlying their differential responses to drugs. Using a fitness landscape determined recently, we estimated that 13 amino acid variants, encoded by 44 codons, exist at the residue 93 of the NS5A protein, illustrating the massive diversity of accessible resistance pathways at specific loci. Accounting for this diversity, which our model enables, would help optimize drug combinations. Our model may be applied to describe the within-host evolution of other flaviviruses and inform vaccine design strategies. [ABSTRACT FROM AUTHOR]

In experimental evolution, scientists evolve organisms in the lab, typically by challenging them to new environmental conditions. How best to evolve a desired trait? Should the challenge be applied abruptly, gradually, periodically, sporadically? Should one apply chemical mutagenesis, and do strains with high innate mutation rate evolve faster? What are ideal population sizes of evolving populations? There are endless strategies, beyond those that can be exposed by individual labs. We therefore arranged a community challenge, Evolthon, in which students and scientists from different labs were asked to evolve Escherichia coli or Saccharomyces cerevisiae for an abiotic stress—low temperature. About 30 participants from around the world explored diverse environmental and genetic regimes of evolution. After a period of evolution in each lab, all strains of each species were competed with one another. In yeast, the most successful strategies were those that used mating, underscoring the importance of sex in evolution. In bacteria, the fittest strain used a strategy based on exploration of different mutation rates. Different strategies displayed variable levels of performance and stability across additional challenges and conditions. This study therefore uncovers principles of effective experimental evolutionary regimens and might prove useful also for biotechnological developments of new strains and for understanding natural strategies in evolutionary arms races between species. Evolthon constitutes a model for community-based scientific exploration that encourages creativity and cooperation. [ABSTRACT FROM AUTHOR]

As the central dogma of molecular biology, genetic information flows from DNA through transcription into RNA followed by translation of the message into protein by transfer RNAs (tRNAs). However, mRNA translation is not always perfect, and errors in the amino acid composition may occur. Mistranslation is generally well tolerated, but once it reaches superphysiological levels, it can give rise to a plethora of diseases. The key causes of mistranslation are errors in translational decoding of the codons in mRNA. Such errors mainly derive from tRNA misdecoding and misacylation, especially when certain codon-paired tRNA species are missing. Substantial progress has recently been made with respect to the mechanistic basis of erroneous mRNA decoding as well as the resulting consequences for physiology and pathology. Here, we aim to review this progress with emphasis on viral evolution and cancer development. [ABSTRACT FROM AUTHOR]

Birds utilize a unique structure, called a syrinx, for the production of their vocalizations. The origins of the syrinx are not well understood. New work, utilizing first principles–based models, suggests that a key element in selection for the early syrinx might be the position of this vocal structure: although the larynx sits at the cranial end of the airway, the avian syrinx is located at the base of the airway at the split of the trachea to the lungs. This position may make the syrinx intrinsically more efficient, which might have been critical in the origin of this anatomical feature. [ABSTRACT FROM AUTHOR]