Biology subjects

Wolf, Y. I.

Publications and source records attributed to Wolf, Y. I..

At least 19 recordsLinked to original sources

bioRxiv2026

Computational modeling of an RNA-peptide world

Emergence and evolution of functional RNA and protein structures are the central problems for understanding the origin of life. Although it is well known that catalytically active RNA elements, ribozymes, can catalyze many reactions, including peptide bond formation, the specifics of the transition from the hypothetical, primordial RNA world to protein-based life centered at the translation system remain enigmatic. We developed AMES, Atomistic Molecular Evolution Simulator, and employed it to perform computer simulations of the evolution of short RNA molecules and RNA-peptide complexes. Comparison of the evolutionary trajectories and the structures of RNA molecules and RNA-peptide complexes emerging in these simulations shows that short random peptides accelerate RNA evolution, stabilize RNA folds, and boost the structural diversity of evolving RNA molecules, potentially enabling a broader range of activities. We hypothesize that the RNA world was, actually, an RNA-peptide world, in which, from the earliest stages of evolution, evolving RNA molecules interacted with short random peptides synthesized in a non-templated manner. These interactions could drive the evolution of diverse RNA structures and activities, and eventually, of the translation machinery.

evolutionary biology↗

bioRxiv2026

Evolutionary implications of phenotype switching for growth and survival of tumors in stochastic environments.

Tumors evolve under constantly changing microenvironmental conditions, and a key major mechanism by which cancer cells adapt to fluctuating environments is stochastic phenotypic switch via epithelial-mesenchymal plasticity (EMP). Here we demonstrate the existence of EMP in human breast epithelial cell lines and assess the fitness of E and M cells in environments that fluctuate between favorable and harsh conditions. We then develop a theoretical framework for analysis of tumor evolution with E-M stochastic phenotypic switch that integrates the behaviors of E and M cells. We characterize the outcomes of tumor evolution via three characteristic times describing i) tumor growth, ii) phenotypic adaptation and iii) fluctuations of the environment. We identify a tradeoff between tumor growth and survival, with different phenotype switching rates maximizing each of these objectives. An anticancer therapeutic strategy is proposed based on tumor survival analysis, revealing that blocking mesenchymal to epithelial transition, rather than epithelial to mesenchymal transition, is critical under fluctuating conditions. Thus, this study elucidates fundamental evolutionary mechanisms of tumor phenotypic adaptation in fluctuating environments with potentially important clinical implications.

evolutionary biology↗

bioRxiv2026

Diversity and evolution of the ribovirian class Stelpaviricetes

Metatranscriptome mining has dramatically expanded the known diversity of ribovirians at all taxonomic levels. We explored in detail the class Stelpaviricetes in the phylum Pisuviricota that so far included 3 orders and 6 recognized virus families, order Stellavirales with family Astroviridae infecting vertebrates, Patatavirales with families Potyviridae, the largest known family of plant ribovirians, and Potyliviridae, and Hypofuvirales consisting of 3 families of viruses associated with phytopathogenic fungi. Using an order-specific collection of Hidden Markov Model profiles for the RNA-dependent RNA polymerase (RdRP), the hallmark protein of ribovirians, we identified 103 putative families within Stelpaviricetes, most of which share a uniform, astrovirus-like genome architecture, encoding three recognizable protein domains, the RdRP, a chymotrypsin-like protease and a single jelly roll capsid protein. The topology of the phylogenetic tree of the RdRP implies that the common ancestor of Stelpaviricetes had an astrovirus-like genome. The ancestor of the order Patatavirales acquired two additional domains, a papain-like protease and a superfamily 2 helicase, whereas the capsid protein was replaced with an unrelated one forming filamentous capsids. The ancestor of Hypofuvirales also encoded a superfamily 2 helicase and, possibly, a papain-like protease, but lost the capsid protein. Hypofuvirales might have derived from Patatavirales or evolved independently from an astro-like ancestor. For the vast majority of Stelpaviricetes identified in metatranscriptomes, host assignment remains elusive. Nevertheless, analysis of endogenous virus elements combined with information on isolated viruses provides some clues, in particular, suggesting that the common ancestor of Potyviridae and Potyliviridae had a fungal host whereas the common ancestor of Stelpaviricetes might have been a protist virus. IMPORTANCEThe enormous diversity of viruses on earth is only now coming to light through extensive metagenome and metatranscriptome mining. Using vast databases of ribovirus genomes, we performed phylogenomic analysis of the class Stelpaviricetes that includes the family of animal viruses Astroviridae and Potyviridae, the largest known family of plant viruses. We identified more than 100 family-level groups of viruses most of which have small, astrovirus-like genomes, likely, resembling the common ancestor of Stelpaviricetes. In contrast, the putative common ancestor of Potyviridae and its sister family Potyliviridae exhibits higher genome complexity that apparently emerged in viruses of fungi. The most plausible scenario for the origin of Potyviridae involves cross-kingdom horizontal virus transfer between plant-associated fungi and plants.

microbiology↗

bioRxiv2026

Eco-evolutionary dynamics of defense systems in mobile genetic elements: Cui bono?

BackgroundMobile genetic elements (MGEs), including viruses, plasmids, and transposons, are major drivers of evolution in bacteria and archaea. Host-parasite conflicts drive the emergence of a broad variety of defense and counter-defense systems. Recent advances in metagenomics and functional annotation have shown that many defense systems are located on MGEs. The fact that MGEs are, essentially, genomic parasites raises an intriguing question: why do these parasites carry defense systems at high prevalence, often even higher than the host chromosome? ResultsWe developed a simple mathematical model to investigate the factors that promote evolution of defense systems in MGEs and the ecological implications of MGE-encoded defense. Our analysis points to the strength of inter-MGE interference as a key determinant of the evolution of defense systems in MGEs. We identify two qualitatively distinct regimes, depending on the basic reproductive number in mixed coinfections. Weakly interfering MGEs tend to carry low-cost defense systems that enhance the survival of their hosts upon exposure to more damaging MGEs. Although these systems can be occasionally transferred to the host, they typically remain in MGEs. In contrast, strongly interfering MGEs, such as plasmids from the same incompatibility group, can carry high-cost defense systems that are detrimental to the host and the population as a whole, but help their carriers spread by actively replacing their competitors. ConclusionsAnalysis of our model shows that the key determinant of the evolution and spread of defense systems in MGEs is the strength of cross-MGE interference. Weakly interfering MGEs would serve as MGE banks, typically carrying low-cost defense systems that can benefit the host by protecting it from more damaging MGEs. In contrast, strongly interfering MGEs would carry costly defense systems that mediate inter-MGE conflicts but are deleterious to the host. These MGEs could serve as proving grounds for emerging defense systems, which might eventually become cost-effective once optimized by selection.

evolutionary biology↗

bioRxiv2026

Hawaiian Geothermal Fumaroles Contain Diverse and Novel Viruses

Microbial communities of geothermal habitats are central to understanding the evolution of life on Earth. Metagenomics has provided insight into the role of viruses in shaping microbial diversity of complex environments. However, identification of novel viruses is constrained by lack of marker genes and low nucleotide similarities between related viral taxa. While microbial and viral diversity have been explored in terrestrial hot springs and hydrothermal vent systems, other volcanic features remain underexplored. Fumaroles (steam vents) are geothermal features that heat groundwater with magma, releasing steam and volcanic gases such as CO2 and H2S. Comparatively physicochemically dynamic to hot springs, fumarole temperatures and gas emissions rapidly fluctuate with volcanic activity. Here, we describe viruses identified metagenomically from microbial mats hosted near basaltic fumaroles on the Big Island of Hawaii. To our knowledge, this is the first systematic survey of fumarole viruses. Our utilization of a sensitive profile-based approach for identification reveals high viral diversity in fumaroles, resulting in estimation of two undescribed order-level clades of Caudoviricetes (tailed phages). Viral metabolic genes provide evidence of viral-mediated adaptation of microbes to fumarole conditions. We describe patterns of viral diversity that diverge from the Bank model of viral ecology, hinting at viral dispersal between biofilms and high viral richness and evenness. Lastly, we provide a description of the first terrestrial geothermal environment dominated by Microviridae, previously only described in viral communities of deep ocean hydrothermal vents. This study offers important findings for exploration of viral ecology in extreme environments.

microbiology↗

bioRxiv2026

Diverse bacterial pattern recognition receptors sense the conserved phage proteome

Recognition of foreign molecules inside cells is critical for immunity across all domains of life. Proteins of the STAND NTPase superfamily1,2, including eukaryotic NOD-like receptors (NLRs), play a central role in this process3,4. In bacteria and archaea, although several STAND families sense phage proteins5-9, their functional diversity remains largely unexplored. We conducted a systematic phylogenetic analysis of prokaryotic STAND NTPases and identified at least 90 structurally distinct families associated with antiviral defense. We first show that the uncharacterized Avs7 family recognizes the major capsid protein (MCP) of tailed phages. Three cryo-EM structures of Salmonella enterica Avs7 reveal an asymmetric, butterfly-shaped tetramer that assembles stepwise via large, MCP-induced conformational changes, incorporating bacterial elongation factor Tu (EF-Tu) as a structural component that enhances defense. Using genetic screens with a library of 687 phage genes, we further show that 13 additional STAND families sense 13 conserved phage proteins, encompassing most of the core structural and replicative components of tailed phages. These include two distinct MCP-sensing families--Avs8 (PD-{lambda}-4) and Avs10 (Erebus/Hypnos/bNACHT64)--and 11 others (Avs11-21) recognizing the portal, portal adaptor, tail nozzle, head-tail connector, tail terminator, tail tube protein, tail assembly chaperone, tape measure protein, DNA polymerase, helicase/RecA-type ATPase, and single-stranded DNA annealing protein, respectively. Together, our findings highlight structurebased pattern recognition and host factor repurposing as fundamental strategies of bacterial immunity.

molecular biology↗

bioRxiv2025

The heterogeneous selection landscape of genome evolution in prokaryotes

Evolution of prokaryote genomes appears to be defined by the interplay of selection for genome streamlining, deletion bias and selection for functional diversification. The previously observed overall positive correlation between the strength of selection, measured as the ratio of non-synonymous to synonymous nucleotide substitutions (dN/dS), points to diversification as the primary factor of prokaryote genome evolution. Here, we investigated the interplay between genome size and selection pressure by analyzing an expanded collection of closely related prokaryotic genomes, evaluating genome-wide selection by measuring dN/dS by using an accurate, phylogeny-based method and decomposing the resulting values into lineage-specific and gene-specific components. These analyses reveal a pronounced heterogeneity in the relationship between genome size and the strength of selection across the diversity of prokaryotes. Most bacteria display a positive correlation consistent with selection for diversification, whereas all analyzed archaeal lineages show strong negative correlation which is the signature of streamlining. These findings indicate that the selection regimes broadly vary across the diversity of prokaryotes rather than following a single, universal pattern. Genome streamlining, selection for functional diversity and drift in small populations are all important factors of evolution, their relative contributions depending on the population genetics and ecology of a given lineage.

evolutionary biology↗

bioRxiv2025

Taxonomy-free fecal microbiome profiles enable robust prediction of immunotherapy response and toxicity in melanoma

The gut microbiome has been causally linked to the efficacy of immune-checkpoint inhibitor therapy (ICI), prompting numerous clinical trials of microbiome-targeting strategies. Yet, mechanisms by which gut microbiota shape immune responses remain elusive as taxonomic biomarkers have failed to generalize across multiple cohorts. In this study, we develop a taxonomy-agnostic framework to identify microbial biomarkers of ICI response and immune-related adverse event (irAE) occurrence from metagenomic sequencing. Applying this approach to four independent melanoma cohorts from clinical centers across the United States, we uncover gut microbial proteins produced by diverse bacterial taxa that consistently predict ICI response. Notably, we uncover a previously uncharacterized operon involved in cellular redox homeostasis that is encoded by different bacteria and reliably predicts irAE occurrence. We further validated the predictive power of this operon in a prospectively sequenced melanoma cohort. Our results demonstrate that taxa-agnostic microbial protein biomarkers are robust, generalizable, and provide a path towards pretreatment risk stratification for melanoma patients initiating ICI therapy.

cancer biology↗

bioRxiv2025

Mosquito vector ecologies are destabilizing as a result of climate change

Mosquito-borne infectious disease is a major cause of mortality and a significant economic burden worldwide. Shifting regional and seasonal patterns make proactive intervention challenging. Here we introduce a machine learning approach trained on satellite and mosquito observational data, improving generalizability to sparse observations while retaining similar positive performance characteristics of models used in standard practice. We provide global estimates for Aedes habitability at high spatial resolution in five-year increments from 1970-2024. The vast majority of ecologies appear to be destabilizing. Overall, we demonstrate a decrease in risk near the equator and an increase in risk in historically temperate climates including the United States, the European Union, and China. Despite this decrease in risk relative to historical averages, regions near the equator remain among the highest risk worldwide. Together, these results reflect an overall, marked expanse of the regions of the globe that support Aedes mosquitos and we observe an ongoing, linear increase in the global population at risk of contracting mosquito-borne disease.

ecology↗

bioRxiv2025

YprA family helicases provide the missing link between diverse prokaryotic immune systems

Bacteria and archaea possess an enormous variety of antivirus immune systems that often share homologous proteins and domains, some of which contribute to diverse defense strategies. YprA family helicases are central to widespread defense systems DISARM, Dpd, and Druantia. Here, through comprehensive phylogenetic and structural prediction analysis of the YprA family, we identify several major, previously unrecognized clades, with unique signatures of domain architecture and associations with other genes. Each YprA family clade defines a distinct class of defense systems, which we denote ARMADA (disARM-related Antiviral Defense Array), BRIGADE (Base hypermodification and Restriction Involving Genes encoding ARMADA-like and Dpd-like Effectors), or TALON (TOTE-like and ARMADA-Like Operon with Nuclease). In addition to the YprA-like helicase, ARMADA systems share two more proteins with DISARM. However, ARMADA YprA homologs are most similar to those of Druantia, suggesting ARMADA is a missing link connecting DISARM and Druantia. We show experimentally that ARMADA protects bacteria against a broad range of phages via a direct, non-abortive mechanism. We also discovered multiple families of satellite phage-like mobile genetic elements that often carry both ARMADA and Druantia Type III systems and show that these can provide synergistic resistance against diverse phages.

microbiology↗

bioRxiv2025

Evolution of antivirus defense in prokaryotes depending on the environmental virus prevalence and virome dynamics

Prokaryotes can acquire antivirus immunity via two fundamentally distinct types of processes: direct interaction with the virus as in CRISPR-Cas adaptive immunity systems and horizontal gene transfer (HGT) which is the main route of transmission of innate immunity systems. These routes of defense evolution are not mutually exclusive and can operate simultaneously, but empirical observations suggest that at least in some bacterial and archaeal species, one or the other route dominates the defense landscape. We hypothesized that the observed dichotomy stems from different life-history tradeoffs characteristic of these organisms. To test this hypothesis, we analyzed a mathematical model of a well-mixed prokaryote population under a stochastically changing viral prevalence. Optimization of the long-term population growth rate reveals two contrasting modes of defense evolution. In stable, predictable and fluctuating, unpredictable environments with a moderate viral prevalence, direct interaction with the virus and horizontal transfer of defense genes become the optimal routes of immunity acquisition, respectively. In the HGT-dominant mode, we observed a universal distribution of the fraction of microbes with different immune repertoires. Under very low virus prevalence, the cost of immunity exceeds the benefits such that the optimal state of a prokaryote is complete defense systems. By contrast, under very high virus prevalence, horizontal spread of defense systems dominates regardless of the stability of the virome. These findings might explain consistent but enigmatic patterns in the spread of antivirus defense systems among prokaryotes such as the ubiquity of adaptive immunity in hyperthermophiles contrasting their patchy distribution among mesophiles. IMPORTANCEThe virus-host arms race is a major component of the evolutionary process in all organisms that drove the evolution of a broad variety of immune mechanisms. In the last few years, over 200 distinct antivirus defense systems have been discovered in prokaryotes. There are two major modes of immunity acquisition: innate immune systems spread through microbial populations via horizontal gene transfer (HGT) whereas adaptive-type immune systems acquire immunity via direct interaction with the virus. We developed a mathematical model to explore the short term evolution of prokaryotic immunity and show that in stable environments with predictable viral repertoires, adaptive-type immunity is the optimal defense strategy whereas in fluctuating environments with unpredictable virus composition, HGT dominates the immune landscape.

evolutionary biology↗

bioRxiv2025

Evolution of gene order in prokaryotes is driven primarily by gene gain and loss

Evolution of bacterial and archaeal genomes is highly dynamic including extensive gene gain via horizontal gene transfer and gene loss as well as different types of genome rearrangements, such as inversions and translocations, so that gene order is not highly conserved even among closely related organisms. We sought to quantify the contributions of different genome dynamics processes to the evolution of the gene order relying on the recently developed "jump" model of gene translocation. The jump model has been completely solved analytically and provides the exact distribution of syntenic gene block lengths (SBL) in compared genomes based on gene translocations alone. Comparing the SBL distribution predicted by the jump model with the distributions empirically observed for multiple groups of closely related bacterial and archaeal genomes, we obtained robust estimates of the genome rearrangement to gene flux (gain and loss) ratio. In most groups of bacteria and archaea, this ratio was found to be on the order of 0.1 indicating that the loss of synteny in the evolution of bacteria and archaea is driven primarily by gene gain and loss rather than by gene translocation. SignificanceEvolution of bacterial and archaeal genomes is a highly dynamic process that includes extensive gene gain via horizontal gene transfer and gene loss as well as different types of genome rearrangements, so that gene order is not highly conserved even among closely related organisms. We developed a theoretical framework to quantify the contributions of different genome dynamics processes to the evolution of the gene order and found that in most groups of bacteria and archaea, the genome rearrangement to gene flux (combined gain and loss) is on the order of 0.1. Thus, the loss of genomic synteny in the evolution of bacteria and archaea appears to be driven primarily by gene gain and loss rather than by gene translocation.

evolutionary biology↗

bioRxiv2025

"Paraxenoviridae", a putative family of ubiquitous marine bacteriophages with double-stranded RNA genomes

Fragmented and primer Ligated DsRNA Sequencing (FLDS) was used to reconstruct five complete, bisegmented RNA genomes of paraxenoviruses, a group of viruses that was previously identified in the ocean and that based on the analysis of partial genomes was proposed to represent a putative new phylum within the kingdom Orthornavirae of the realm Riboviria. Phylogenetic analysis of the RNA-directed RNA polymerases of paraxenoviruses demonstrated their affinity with the ribovirus order Durnavirales within the class Duplopiviricetes of the phylum Pisuviricota. The order Durnavirales includes families Cystoviridae that consists of well-characterized dsRNA bacteriophages and less thoroughly studied Picobirnaviridae that are also suspected to infect bacteria. Consistently, modeling and analysis of the structure of the predicted capsid protein (CP) of several paraxenoviruses revealed similarity to picobirnavirus CP although the paraxenovirus CP is much larger and contains unique structural elaborations. Taken together, these affinities suggest that paraxenoviruses represent a distinct family within Durnavirales, which we provisionally name "Paraxenoviridae". Both genomic segments in Picobirnaviridae and "Paraxenoviridae" encompass multiple open reading frames, each preceded by a typical bacterial ribosome-binding site, strongly suggesting that these families consist of bacterial viruses. Search for homologs of paraxenovirus genes shows widespread distribution of this virus group in the global ocean, suggesting a potential important contribution to marine microbial ecosystems. Our findings further expand the diversity and ecological role of the bacterial RNA virome, reveal extensive structural variability of RNA viral capsid proteins, and demonstrate the common ancestry of several distinct families of bacterial viruses with dsRNA genomes.

microbiology↗

bioRxiv2024

In silico evolution of globular protein folds from random sequences

The origin and evolution of protein folds are among the most challenging, long-standing problems in biology 1,2. Although many plausible scenarios of early protein evolution leading to fold nucleation have been proposed 3-8, realistic simulation of this process was not feasible because of the lack of efficient approaches for protein structure prediction, a situation that changed with the advent of powerful tools for fast and robust protein structure prediction, such as AlphaFold 9,10 and ESMFold11. We developed a computational approach for protein fold evolution simulator (PFES) with atomistic details that provide insights into the mechanisms of evolution of globular folds from random amino acid sequences. PFES introduces random mutations in a population of protein sequences, evaluates the effect of mutations on protein structure, and selects a new set of proteins for further evolution. Repeating this process iteratively allows tracking the evolutionary trajectory of a changing protein fold that evolves under selective pressure for protein fold stability, interaction with other proteins, or other features shaping the fitness landscape. We employed PFES to show how globular protein folds could evolve from random amino acid sequences as monomers or in complexes with other proteins. The simulations reproduce the evolution of many simple folds of natural proteins as well as the evolution of distinct folds not known to exist in nature. We show that evolution of a stable fold from random sequences, on average takes 3 to 8 amino acid replacements per site, suggesting that simple but stable protein folds can evolve relatively easily. These findings could shed light on the enigma of the rapid evolution of protein fold diversity at the earliest stages of life evolution. PFES tracks the complete evolutionary history from simulations that describes intermediate states at the sequence and structure levels and can be used to test versatile hypotheses on protein fold evolution.

evolutionary biology↗

bioRxiv2024

Ecological Determinants of Altruism in Prokaryote Antivirus Defense

Prokaryote evolution is driven in large part by the incessant arms race with viruses. Genomic investments in antivirus defense can be coarsely classified into two categories, immune systems that abrogate virus reproduction resulting in clearance, and altruistic programmed cell death (PCD) systems. Prokaryotic defense systems are enormously diverse, as revealed by an avalanche of recent discoveries, but the basic ecological determinants of defense strategy remain poorly understood. Through mathematical modeling of defense against lytic virus infection, we identify two principal determinants of optimal defense strategy and, through comparative genomics, we test this model by measuring the genomic investment into immunity vs PCD among diverse bacteria and archaea. First, as viral pressure grows, immunity becomes the preferred defense strategy. Second, as host population size grows, PCD becomes the preferred strategy. We additionally predict that, although optimal strategy typically involves investment in both PCD and immunity, overinvestment in immunity can result in system antagonism, increasing the probability a PCD-competent cell will lyse due to infection. Together these findings indicate that, generally, PCD is preferred at low multiplicity of infection (MOI) and immunity is preferred at high MOI, and that the landscape of prokaryotic antivirus defense is substantially more complex than previously suspected.

microbiology↗

bioRxiv2024

The key role of cheaters in the persistence of cooperation

Evolution of cooperation is a major, extensively studied problem in evolutionary biology. Cooperation is beneficial for a population as a whole but costly for the bearers of social traits such that cheaters enjoy a selective advantage over cooperators. Here we focus on coevolution of cooperators and cheaters in a multi-level selection framework, by modeling competition among groups composed of cooperators and cheaters. Cheaters enjoy a reproductive advantage over cooperators at the individual level, independent of the presence of cooperators in the group. Cooperators carry a social trait that provides a fitness advantage to the respective groups. In the case of absolute fitness advantage, where the survival probability of a group is independent of the composition of other groups, the survival of cooperators does not correlate with the presence of cheaters. By contrast, in the case of relative fitness advantage, where the survival probability of a group depends on the composition of all groups, the survival of cooperators positively correlates with the presence of cheaters. Increasing the strength of the social trait alone fails to ensure survival of cooperators, and the increase of the reproduction advantage of the cheaters is necessary to avoid population extinction. We validate these theoretical results with an agent-based model of a bacterial biofilm where emergence of the cooperative trait is facilitated by the presence of cheaters, leading to evolution of spatial organization. This finding contrasts the classical view that spatial organization facilitates cooperation. Our results suggest that, counterintuitively, cheaters often promote, not destabilize, evolution of cooperation. SignificanceCooperation is central to the evolution of life and the emergence of multicellularity. Social traits stabilize populations against environmental volatility and enable division of labor. However, evolution of cooperation is beset by cheaters that benefit from cooperation without paying the cost. Analysis of a multilevel selection model of population evolution shows that, counterintuitively, the presence of cheaters can be beneficial or even essential for the survival of cooperators. This unexpected effect comes from multilevel selection whereby cheaters at the individual level become altruists at the group level, enabling overall growth of the population that is essential for the persistence of cooperators. These findings have broad implications for understanding the emergence of cooperation and host-parasite coevolution throughout the history of life.

evolutionary biology↗

bioRxiv2024

Dominant contribution of Asgard archaea to eukaryogenesis

The origin of eukaryotes is one of the key problems in evolutionary biology 1,2. The demonstration that the Last Eukaryotic Common Ancestor (LECA) already contained the mitochondrion, an endosymbiotic organelle derived from an alphaproteobacterium, and the discovery of Asgard archaea, the closest archaeal relatives of eukaryotes 3-7, inform and constrain evolutionary scenarios of eukaryogenesis 8. We undertook a comprehensive analysis of the origins of core eukaryotic genes tracing to the LECA within a rigorous statistical framework centered around evolutionary hypotheses testing using constrained phylogenetic trees. The results reveal dominant contributions of Asgard archaea to the origin of most of the conserved eukaryotic functional systems and pathways. A limited contribution from Alphaproteobacteria was identified, primarily relating to the energy transformation systems and Fe-S cluster biogenesis, whereas ancestry from other bacterial phyla was scattered across the eukaryotic functional landscape, without clear consistent trends. These findings suggest a model of eukaryogenesis in which key features of eukaryotic cell organization evolved in the Asgard lineage leading to the LECA, followed by the capture of the Alphaproteobacterial endosymbiont, and augmented by numerous but sporadic horizontal acquisition of genes from other bacteria both before and after endosymbiosis.

evolutionary biology↗

bioRxiv2024

The protein structurome of Orthornavirae and its dark matter

Metatranscriptomics is uncovering more and more diverse families of viruses with RNA genomes comprising the viral kingdom Orthornavirae in the realm Riboviria. Thorough protein annotation and comparison are essential to get insights into the functions of viral proteins and virus evolution. In addition to sequence- and hmm profile-based methods, protein structure comparison adds a powerful tool to uncover protein functions and relationships. We constructed an Orthornavirae structurome consisting of already annotated as well as unannotated ( dark matter) proteins and domains encoded in viral genomes. We used protein structure modeling and similarity searches to illuminate the remaining dark matter in hundreds of thousands of orthornavirus genomes. The vast majority of the dark matter domains showed either generic folds, such as single -helices, or no high confidence structure predictions. Nevertheless, a variety of lineage-specific globular domains that were new either to orthornaviruses in general or to particular virus families were identified within the proteomic dark matter of orthornaviruses, including several predicted nucleic acid-binding domains and nucleases. In addition, we identified a case of exaptation of a cellular nucleoside monophosphate kinase as an RNA-binding protein in several virus families. Notwithstanding the continuing discovery of numerous orthornaviruses, it appears that all the protein domains conserved in large groups of viruses have already been identified. The rest of the viral proteome seems to be dominated by poorly structured domains including intrinsically disordered ones that likely mediate specific virus-host interactions. IMPORTANCEAdvanced methods for protein structure prediction, such as AlphaFold2, greatly expand our capability to identify protein domains and infer their likely functions and evolutionary relationships. This is particularly pertinent for proteins encoded by viruses that are known evolve rapidly and as a result often cannot be adequately characterized by analysis of the protein sequences. We performed an exhaustive structure prediction and comparative analysis for uncharacterized proteins and domains ( dark matter) encoded by viruses with RNA genomes. The results show the dark matter of RNA virus proteome consists mostly of disordered and all -helical domains that cannot be readily assigned a specific function and that likely mediate various interactions between viral proteins and between viral and host proteins. The great majority of globular proteins and domains of RNA viruses are already known although we identified several unexpected domains represented in individual viral families.

evolutionary biology↗