Biology subjects

Wolf, Y. I.

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

10 recordsLinked to original sources

bioRxiv2018

Origins and Evolution of the Global RNA Virome

Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches, 2 of which include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded (ds) RNA viruses, and 2 consist of dsRNA and negative-sense (-) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas -RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, particularly, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy.\n\nIMPORTANCEThe majority of the diverse viruses infecting eukaryotes have RNA genomes, including numerous human, animal, and plant pathogens. Recent advances of metagenomics have led to the discovery of many new groups of RNA viruses in a wide range of hosts. These findings enable a far more complete reconstruction of the evolution of RNA viruses than what was attainable previously. This reconstruction reveals the relationships between different Baltimore Classes of viruses and indicates extensive transfer of viruses between distantly related hosts, such as plants and animals. These results call for a major revision of the existing taxonomy of RNA viruses.

microbiology↗

bioRxiv2018

Stability of host-parasite systems: you must differ to coevolve

BackgroundGenetic parasites are ubiquitous satellites of cellular life forms most of which host a variety of mobile genetic elements including transposons, plasmids and viruses. Theoretical considerations and computer simulations suggest that emergence of genetic parasites is intrinsic to evolving replicator systems.\n\nResultsUsing methods of bifurcation analysis, we investigated the stability of simple models of replicator-parasite coevolution in a well-mixed environment. It is shown that the simplest imaginable system of this type, one in which the parasite evolves during the replication of the host genome through a minimal mutation that renders the genome of the emerging parasite incapable of producing the replicase but able to recognize and recruit it for its own replication, is unstable. In this model, there are only either trivial or \"semi-trivial\", parasite-free equilibria: an inefficient parasite is outcompeted by the host and dies off whereas an efficient one pushes the host out of existence, which leads to the collapse of the entire system. We show that stable host-parasite coevolution (a non-trivial equilibrium) is possible in a modified model where the parasite is qualitatively distinct from the host replicator in that the replication of the parasite depends solely on the availability of the host but not on the carrying capacity of the environment.\n\nConclusionsWe analytically determine the conditions for stable host-parasite coevolution in simple mathematical models and find that a parasite that initially evolves from the host through the loss of the ability to replicate autonomously must be substantially derived for a stable host-parasite coevolution regime to be established.

evolutionary biology↗

bioRxiv2018

On the feasibility of saltational evolution

One of the key tenets of Darwins theory that was inherited by the Modern Synthesis of evolutionary biology is gradualism, that is, the notion that evolution proceeds gradually, via accumulation of \"infinitesimally small\" heritable changes 1,2. However, some of the most consequential evolutionary changes, such as, for example, the emergence of major taxa, seem to occur abruptly rather than gradually, as captured in the concepts of punctuated equilibrium 3,4 and evolutionary transitions 5,6. We examine a mathematical model of an evolutionary process on a rugged fitness landscape 7,8 and obtain analytic solutions for the probability of multi-mutational leaps, that is, several mutations occurring simultaneously, within a single generation in one genome, and being fixed all together in the evolving population. The results indicate that, for typical, empirically observed combinations of the parameters of the evolutionary process, namely, effective population size, mutation rate, and distribution of selection coefficients of mutations, the probability of a multi-mutational leap is low, and accordingly, their contribution to the evolutionary process is minor at best. However, such leaps could become an important factor of evolution in situations of population bottlenecks and elevated mutation rates, such as stress-induced mutagenesis in microbes or tumor progression, as well as major evolutionary transitions and evolution of primordial replicators.

evolutionary biology↗

bioRxiv2018

Genome plasticity, a key factor of evolution in prokaryotes

In prokaryotic genomes, the number of genes that belong to distinct functional classes shows apparent universal scaling with the total number of genes [1-5] (Fig. 1). This scaling can be approximated with a power law, where the scaling power can be sublinear, near-linear or super-linear. Scaling laws are robust under various statistical tests [4], across different databases and for different gene classifications [1-5]. Several models aimed at explaining the observed scaling laws have been proposed, primarily, based on the specifics of the respective biological functions [1, 5-8]. However, a coherent theory to explain the emergence of scaling within the framework of population genetics is lacking. We employ a simple mathematical model for prokaryotic genome evolution [9] which, together with the analysis of 34 clusters of closely related microbial genomes [10], allows us to identify the underlying forces that dictate genome content evolution. In addition to the scaling of the number of genes in different functional classes, we explore gene contents divergence to characterize the evolutionary processes acting upon genomes [11]. We find that evolution of the gene content is dominated by two factors that are specific to a functional class, namely, selection landscape and genome plasticity. Selection landscape quantifies the fitness cost that is associated with deletion of a gene in a given functional class or the advantage of successful incorporation of an additional gene. Genome plasticity, that can be considered a measure of evolvability, reflects both the availability of the genes of a given functional class in the external gene pool that is accessible to the evolving microbial population, and the ability of microbial genomes to accommodate these genes. The selection landscape determines the gene loss rate, and genome plasticity is the principal determinant of the gene gain rate.\n\nO_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC=\"FIGDIR/small/357400_fig1.gif\" ALT=\"Figure 1\">\nView larger version (39K):\norg.highwire.dtl.DTLVardef@6df3e2org.highwire.dtl.DTLVardef@a69e8dorg.highwire.dtl.DTLVardef@f36a80org.highwire.dtl.DTLVardef@d519c9_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Scaling laws for all functional classes of the COGs. The number of genes in a given COG category is plotted against the total number of genes. Each point represents one genome from the analyzed set of 1490 genomes. The scaling is fitted to a power law which is indicated by a solid red line. The fitted scaling exponent is indicated in parentheses.\n\nC_FIG

microbiology↗

bioRxiv2018

Criticality in Tumor Evolution and Clinical Outcome

How mutation and selection determine the fitness landscape of tumors and hence clinical outcome is an open fundamental question in cancer biology, crucial for the assessment of therapeutic strategies and resistance to treatment. Here we explore the mutation-selection phase-diagram of 6721 primary tumors representing 23 cancer types, by quantifying the overall somatic point mutation load (ML) and selection (dN/dS) in the entire proteome of each tumor. We show that ML strongly correlates with patient survival, revealing two opposing regimes around a critical point. In low ML cancers, high number of mutations indicates poor prognosis, whereas high ML cancers show the opposite trend, due to mutational meltdown. Although the majority of cancers evolve near neutrality, deviations are observed at extreme MLs. Cancers with the highest ML evolve under purifying selection, whereas those with the lowest ML show signatures of positive selection, demonstrating how selection affects cancer fitness. Moreover, different cancers occupy specific positions on the ML-dN/dS plane, revealing a diversity of evolutionary trajectories. These results support and expand the theory of tumor evolution and its non-linear effects on survival.\n\nSignificance StatementIt remains an open fundamental question how mutation and selection co-determine the course of cancer evolution. We construct a selection-mutation phase diagram, using tumor mutation load and selection strength as key variables, and assess their association with clinical outcome. We demonstrate the existence of a biphasic evolutionary regime, whereby beyond a critical ML, the fitness of tumors decreases with the number of mutations, while the proteome evolves near neutrality. Deviations from neutrality in extreme ML elucidate how positive and purifying selections maintain tumor fitness. These results empirically corroborate the existence of a critical state in cancer evolution predicted by theory, and have fundamental and likely clinical implications.

cancer biology↗

bioRxiv2018

Towards comprehensive characterization of CRISPR-linked genes

The CRISPR-Cas systems of bacterial and archaeal adaptive immunity consist of arrays of direct repeats separated by unique spacers and multiple CRISPR-associated (cas) genes encoding proteins that mediate the adaptation, CRISPR RNA maturation and interference stages of the CRISPR response. In addition to the relatively small set of core cas genes that are typically present in all representatives of each (sub)type of CRISPR-Cas systems and are essential for the defense function, numerous genes occur in CRISPR-cas loci only sporadically. Some of these have been shown to perform various ancillary roles in CRISPR response whereas the functional relevance of many others, if any, remains obscure. We developed a computational strategy for systematically detecting genes that are likely to be functionally linked to CRISPR-Cas systems. The approach is based on a \"CRISPRicity\" metric that measures the strength of CRISPR association for all protein-coding genes from sequenced bacterial and archaeal genomes. Uncharacterized genes with CRISPRicity values comparable to those of known cas genes are considered candidate CRISPR-ancillary genes, and we describe additional criteria to identify functionally relevant genes in the candidate set. About 80 genes that were not previously reported to be associated with CRISPR-Cas were identified as probable CRISPR-ancillary genes. A substantial majority of these genes reside in type III CRISPR-cas loci which implies exceptional functional versatility of type III systems. Numerous candidate CRISPR-ancillary genes encode integral membrane proteins suggestive of tight membrane connections of type III CRISPR-Cas whereas many other candidates are proteins implicated in various signal transduction pathways. These predictions provide ample material for improving annotation of CRISPR-cas loci and experimental characterization of previously unsuspected aspects of CRISPR-Cas functionality.\n\nSIGNIFICANCEThe CRISPR-Cas systems that mediate adaptive immunity in bacteria and archaea encompass a small set of core cas genes that are essential in a broad range of CRISPR-Cas systems. However, a much greater number of genes only sporadically co-occur with CRISPR-Cas, and for most of these, involvement in CRISPR-Cas functions has not been demonstrated. We developed a computational strategy that provides for systematic identification of CRISPR-linked proteins and prediction of their functional association with CRISPR-Cas systems. About 80 previously undetected, putative CRISPR-accessory proteins were identified. A large fraction of these proteins are predicted to be membrane-associated revealing an unknown side of CRISPR biology.

genomics↗

bioRxiv2017

Towards physical principles of biological evolution

Biological systems reach organizational complexity that far exceeds the complexity of any known inanimate objects. Biological entities undoubtedly obey the laws of quantum physics and statistical mechanics. However, is modern physics sufficient to adequately describe, model and explain the evolution of biological complexity? Detailed parallels have been drawn between statistical thermodynamics and the population-genetic theory of biological evolution. Based on these parallels, we outline new perspectives on biological innovation and major transitions in evolution, and introduce a biological equivalent of thermodynamic potential that reflects the innovation propensity of an evolving population. Deep analogies have been suggested to also exist between the properties of biological entities and processes, and those of frustrated states in physics, such as glasses. Such systems are characterized by frustration whereby local state with minimal free energy conflict with the global minimum, resulting in \"emergent phenomena\". We extend such analogies by examining frustration-type phenomena, such as conflicts between different levels of selection, in biological evolution. These frustration effects appear to drive the evolution of biological complexity. We further address evolution in multidimensional fitness landscapes from the point of view of percolation theory and suggest that percolation at level above the critical threshold dictates the tree-like evolution of complex organisms. Taken together, these multiple connections between fundamental processes in physics and biology imply that construction of a meaningful physical theory of biological evolution might not be a futile effort. However, it is unrealistic to expect that such a theory can be created in one scoop; if it ever comes to being, this can only happen through integration of multiple physical models of evolutionary processes. Furthermore, the existing framework of theoretical physics is unlikely to suffice for adequate modeling of the biological level of complexity, and new developments within physics itself are likely to be required.

evolutionary biology↗

bioRxiv2017

Inevitability of the emergence and persistence of genetic parasites caused by thermodynamic instability of parasite-free states

Genetic parasites, including viruses and mobile genetic elements, are ubiquitous among cellular life forms, and moreover, are the most abundant biological entities on earth that harbor the bulk of the genetic diversity. Here we examine simple thought experiments to demonstrate that both the emergence of parasites in simple replicator systems and their persistence in evolving life forms are inevitable because the putative parasite-free states are thermodynamically unstable.

evolutionary biology↗

bioRxiv2017

The CRISPR Spacer Space Is Dominated By Sequences From The Species-Specific Mobilome

The CRISPR-Cas is the prokaryotic adaptive immunity system that stores memory of past encounters with foreign DNA in spacers that are inserted between direct repeats in CRISPR arrays 1,2. Only for a small fraction of the spacers, homologous sequences, termed protospacers, are detectable in viral, plasmid or microbial genomes 3,4. The rest of the spacers remain the CRISPR \"dark matter\". We performed a comprehensive analysis of the spacers from all CRISPR-cas loci identified in bacterial and archaeal genomes, and found that, depending on the CRISPR-Cas subtype and the prokaryotic phylum, protospacers were detectable for 1 to about 19% of the spacers ([~]7% global average). Among the detected protospacers, the majority, typically, 80 to 90%, originate from viral genomes, and among the rest, the most common source are genes integrated in microbial chromosomes but involved in plasmid conjugation or replication. Thus, almost all spacers with identifiable protospacers target mobile genetic elements (MGE). The GC-content, as well as dinucleotide and tetranucleotide compositions, of microbial genomes, their spacer complements, and the cognate viral genomes show a nearly perfect correlation and are almost identical. Given the near absence of self-targeting spacers, these findings are best compatible with the possibility that the spacers, including the dark matter, are derived almost completely from the species-specific microbial mobilomes.

microbiology↗

bioRxiv2017

Estimation Of Universal And Taxon-Specific Parameters Of Prokaryotic Genome Evolution

Our recent study on mathematical modeling of microbial genome evolution indicated that, on average, genomes of bacteria and archaea evolve in the regime of mutation-selection balance defined by positive selection coefficients associated with gene acquisition that is counter-acted by the intrinsic deletion bias. This analysis was based on the strong assumption that parameters of genome evolution are universal across the diversity of bacteria and archaea, and yielded extremely low values of the selection coefficient. Here we further refine the modeling approach by taking into account evolutionary factors specific for individual groups of microbes using two independent fitting strategies, an ad hoc hard fitting scheme and an hierarchical Bayesian model. The resulting estimate of the mean selection coefficient of s[~]10-10 associated with the gain of one gene implies that, on average, acquisition of a gene is beneficial, and that microbial genomes typically evolve under a weak selection regime that might transition to strong selection in highly abundant organisms with large effective population sizes. The apparent selective pressure towards larger genomes is balanced by the deletion bias, which is estimated to be consistently greater than unity for all analyzed groups of microbes. The estimated values of s are more realistic than the lower values obtained previously, indicating that global and group-specific evolutionary factors synergistically affect microbial genome evolution that seems to be driven primarily by adaptation to existence in diverse niches.

evolutionary biology↗