http://www.biology-direct.com The most accessed research articles published by Biology Direct 2012-01-20T00:00:00Z Background: Our current understanding of evolution is so tightly linked to template-dependent replication of DNA and RNA molecules that the old idea from Oparin of a self-reproducing 'garbage bag' ('coacervate') of chemicals that predated fully-fledged cell-like entities seems to be farfetched to most scientists today. However, this is exactly the kind of scheme we propose for how Darwinian evolution could have occurred prior to template replication. Results: We cannot confirm previous claims that autocatalytic sets of organic polymer molecules could undergo evolution in any interesting sense by themselves. While we and others have previously imagined inhibition would result in selectability, we found that it produced multiple attractors in an autocatalytic set that cannot be selected for. Instead, we discovered that if general conditions are satisfied, the accumulation of adaptations in chemical reaction networks can occur. These conditions are the existence of rare reactions producing viable cores (analogous to a genotype), that sustains a molecular periphery (analogous to a phenotype). Conclusions: We conclude that only when a chemical reaction network consists of many such viable cores, can it be evolvable. When many cores are enclosed in a compartment there is competition between cores within the same compartment, and when there are many compartments, there is between-compartment competition due to the phenotypic effects of cores and their periphery at the compartment level. Acquisition of cores by rare chemical events, and loss of cores at division, allows macromutation, limited heredity and selectability, thus explaining how a poor man's natural selection could have operated prior to genetic templates. This is the only demonstration to date of a mechanism by which pre-template accumulation of adaptation could occur.ReviewersThis article was reviewed by William Martin and Eugene Koonin. http://www.biology-direct.com/content/7/1/1 Vera Vasas Chrisantha Fernando Mauro Santos Stuart Kauffman Eors Szathmary Biology Direct 2012, null:1 2012-01-05T00:00:00Z doi:10.1186/1745-6150-7-1 /content/figures/1745-6150-7-1-toc.gif Biology Direct 1745-6150 ${item.volume} 1 2012-01-05T00:00:00Z PDF Background: Recent advances in genomics of viruses and cellular life forms have greatly stimulated interest in the origins and evolution of viruses and, for the first time, offer an opportunity for a data-driven exploration of the deepest roots of viruses. Here we briefly review the current views of virus evolution and propose a new, coherent scenario that appears to be best compatible with comparative-genomic data and is naturally linked to models of cellular evolution that, from independent considerations, seem to be the most parsimonious among the existing ones. Results: Several genes coding for key proteins involved in viral replication and morphogenesis as well as the major capsid protein of icosahedral virions are shared by many groups of RNA and DNA viruses but are missing in cellular life forms. On the basis of this key observation and the data on extensive genetic exchange between diverse viruses, we propose the concept of the ancient virus world. The virus world is construed as a distinct contingent of viral genes that continuously retained its identity throughout the entire history of life. Under this concept, the principal lineages of viruses and related selfish agents emerged from the primordial pool of primitive genetic elements, the ancestors of both cellular and viral genes. Thus, notwithstanding the numerous gene exchanges and acquisitions attributed to later stages of evolution, most, if not all, modern viruses and other selfish agents are inferred to descend from elements that belonged to the primordial genetic pool. In this pool, RNA viruses would evolve first, followed by retroid elements, and DNA viruses. The Virus World concept is predicated on a model of early evolution whereby emergence of substantial genetic diversity antedates the advent of full-fledged cells, allowing for extensive gene mixing at this early stage of evolution. We outline a scenario of the origin of the main classes of viruses in conjunction with a specific model of precellular evolution under which the primordial gene pool dwelled in a network of inorganic compartments. Somewhat paradoxically, under this scenario, we surmise that selfish genetic elements ancestral to viruses evolved prior to typical cells, to become intracellular parasites once bacteria and archaea arrived at the scene. Selection against excessively aggressive parasites that would kill off the host ensembles of genetic elements would lead to early evolution of temperate virus-like agents and primitive defense mechanisms, possibly, based on the RNA interference principle. The emergence of the eukaryotic cell is construed as the second melting pot of virus evolution from which the major groups of eukaryotic viruses originated as a result of extensive recombination of genes from various bacteriophages, archaeal viruses, plasmids, and the evolving eukaryotic genomes. Again, this vision is predicated on a specific model of the emergence of eukaryotic cell under which archaeo-bacterial symbiosis was the starting point of eukaryogenesis, a scenario that appears to be best compatible with the data. Conclusion: The existence of several genes that are central to virus replication and structure, are shared by a broad variety of viruses but are missing from cellular genomes (virus hallmark genes) suggests the model of an ancient virus world, a flow of virus-specific genes that went uninterrupted from the precellular stage of life's evolution to this day. This concept is tightly linked to two key conjectures on evolution of cells: existence of a complex, precellular, compartmentalized but extensively mixing and recombining pool of genes, and origin of the eukaryotic cell by archaeo-bacterial fusion. The virus world concept and these models of major transitions in the evolution of cells provide complementary pieces of an emerging coherent picture of life's history.ReviewersW. Ford Doolittle, J. Peter Gogarten, and Arcady Mushegian. http://www.biology-direct.com/content/1/1/29 Eugene Koonin Tatiana Senkevich Valerian Dolja Biology Direct 2006, null:29 2006-09-19T00:00:00Z doi:10.1186/1745-6150-1-29 /content/figures/1745-6150-1-29-toc.gif Biology Direct 1745-6150 ${item.volume} 29 2006-09-19T00:00:00Z XML Life is a chemical reaction. Three major transitions in early evolution are considered without recourse to a tree of life. The origin of prokaryotes required a steady supply of energy and electrons, probably in the form of molecular hydrogen stemming from serpentinization. Microbial genome evolution is not a treelike process because of lateral gene transfer and the endosymbiotic origins of organelles. The lack of true intermediates in the prokaryote-to-eukaryote transition has a bioenergetic cause.This article was reviewed by Dan Graur, W. Ford Doolittle, Eugene V. Koonin and Christophe Malaterre. http://www.biology-direct.com/content/6/1/36 William Martin Biology Direct 2011, null:36 2011-06-30T00:00:00Z doi:10.1186/1745-6150-6-36 /content/figures/1745-6150-6-36-toc.gif Biology Direct 1745-6150 ${item.volume} 36 2011-06-30T00:00:00Z XML Background: As a key parameter of genome sequence variation, the GC content of bacterial genomes has been investigated for over half a century, and many hypotheses have been put forward to explain this GC content variation and its relationship to other fundamental processes. Previously, we classified eubacteria into dnaE-based groups (the dimeric combination of DNA polymerase III alpha subunits), according to a hypothesis where GC content variation is essentially governed by genome replication and DNA repair mechanisms. Further investigation led to the discovery that two major mutator genes, polC and dnaE2, may be responsible for genomic GC content variation. Consequently, an in-depth analysis was conducted to evaluate various potential intrinsic and extrinsic factors in association with GC content variation among eubacterial genomes. Results: Mutator genes, especially those with dominant effects on the mutation spectra, are biased towards either GC or AT richness, and they alter genomic GC content in the two opposite directions. Increased bacterial genome size (or gene number) appears to rely on increased genomic GC content; however, it is unclear whether the changes are directly related to certain environmental pressures. Certain environmental and bacteriological features are related to GC content variation, but their trends are more obvious when analyzed under the dnaE-based grouping scheme. Most terrestrial, plant-associated, and nitrogen-fixing bacteria are members of the dnaE1|dnaE2 group, whereas most pathogenic or symbiotic bacteria in insects, and those dwelling in aquatic environments, are largely members of the dnaE1|polV group. Conclusion: Our studies provide several lines of evidence indicating that DNA polymerase III alpha subunit and its isoforms participating in either replication (such as polC) or SOS mutagenesis/translesion synthesis (such as dnaE2), play dominant roles in determining GC variability. Other environmental or bacteriological factors, such as genome size, temperature, oxygen requirement, and habitat, either play subsidiary roles or rely indirectly on different mutator genes to fine-tune the GC content. These results provide a comprehensive insight into mechanisms of GC content variation and the robustness of eubacterial genomes in adapting their ever-changing environments over billions of years.ReviewersThis paper was reviewed by Nicolas Galtier, Adam Eyre-Walker, and Eugene Koonin. http://www.biology-direct.com/content/7/1/2 Hao Wu Zhang Zhang Songnian Hu Jun Yu Biology Direct 2012, null:2 2012-01-10T00:00:00Z doi:10.1186/1745-6150-7-2 New large-scale comparative genome analyses provided further evidences indicating that polymerases involved in either replication or repair pathways underlie the GC content variability in eubacteria. /content/figures/1745-6150-7-2-toc.gif Biology Direct 1745-6150 ${item.volume} 2 2012-01-10T00:00:00Z PDF Background: The RNA world concept has wide, though certainly not unanimous, support within the origin-of-life scientific community. One view is that life may have emerged as early as the Hadean Eon 4.3-3.8 billion years ago with an atmosphere of high CO2 producing an acidic ocean of the order of pH 3.5-6. Compatible with this scenario is the intriguing proposal that life arose near alkaline (pH 9-11) deep-sea hydrothermal vents like those of the 'Lost City', with the interface with the acidic ocean creating a proton gradient sufficient to drive the first metabolism. However, RNA is most stable at pH 4-5 and is unstable at alkaline pH, raising the possibility that RNA may have first arisen in the acidic ocean itself (possibly near an acidic hydrothermal vent), acidic volcanic lake or comet pond. As the Hadean Eon progressed, the ocean pH is inferred to have gradually risen to near neutral as atmospheric CO2 levels decreased.Presentation of the hypothesisWe propose that RNA is well suited for a world evolving at acidic pH. This is supported by the enhanced stability at acidic pH of not only the RNA phosphodiester bond but also of the aminoacyl-(t)RNA and peptide bonds. Examples of in vitro-selected ribozymes with activities at acid pH have recently been documented. The subsequent transition to a DNA genome could have been partly driven by the gradual rise in ocean pH, since DNA has greater stability than RNA at alkaline pH, but not at acidic pH.Testing the hypothesisWe have proposed mechanisms for two key RNA world activities that are compatible with an acidic milieu: (i) non-enzymatic RNA replication of a hemi-protonated cytosine-rich oligonucleotide, and (ii) specific aminoacylation of tRNA/hairpins through triple helix interactions between the helical aminoacyl stem and a single-stranded aminoacylating ribozyme.Implications of the hypothesisOur hypothesis casts doubt on the hypothesis that RNA evolved in the vicinity of alkaline hydrothermal vents. The ability of RNA to form protonated base pairs and triples at acidic pH suggests that standard base pairing may not have been a dominant requirement of the early RNA world.ReviewersThis article was reviewed by Eugene Koonin, Anthony Poole and Charles Carter (nominated by David Ardell). http://www.biology-direct.com/content/7/1/4 Harold Bernhardt Warren Tate Biology Direct 2012, null:4 2012-01-20T00:00:00Z doi:10.1186/1745-6150-7-4 The greater stability of key RNA bonds at acidic pH, such as link the phosphodiester backbone and between amino acids and tRNA, suggests the RNA world evolved in acidic conditions. /content/figures/1745-6150-7-4-toc.gif Biology Direct 1745-6150 ${item.volume} 4 2012-01-20T00:00:00Z PDF Background: Many of the mutations accumulated by naturally evolving proteins are neutral in the sense that they do not significantly alter a protein's ability to perform its primary biological function. However, new protein functions evolve when selection begins to favor other, "promiscuous" functions that are incidental to a protein's original biological role. If mutations that are neutral with respect to a protein's primary biological function cause substantial changes in promiscuous functions, these mutations could enable future functional evolution. Results: Here we investigate this possibility experimentally by examining how cytochrome P450 enzymes that have evolved neutrally with respect to activity on a single substrate have changed in their abilities to catalyze reactions on five other substrates. We find that the enzymes have sometimes changed as much as four-fold in the promiscuous activities. The changes in promiscuous activities tend to increase with the number of mutations, and can be largely rationalized in terms of the chemical structures of the substrates. The activities on chemically similar substrates tend to change in a coordinated fashion, potentially providing a route for systematically predicting the change in one activity based on the measurement of several others. Conclusion: Our work suggests that initially neutral genetic drift can lead to substantial changes in protein functions that are not currently under selection, in effect poising the proteins to more readily undergo functional evolution should selection favor new functions in the future.ReviewersThis article was reviewed by Martijn Huynen, Fyodor Kondrashov, and Dan Tawfik (nominated by Christoph Adami). http://www.biology-direct.com/content/2/1/17 Jesse Bloom Philip Romero Zhongyi Lu Frances Arnold Biology Direct 2007, null:17 2007-06-28T00:00:00Z doi:10.1186/1745-6150-2-17 /content/figures/1745-6150-2-17-toc.gif Biology Direct 1745-6150 ${item.volume} 17 2007-06-28T00:00:00Z XML Background: Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one or more prior forecasts. We consider the potential feasibility of this approach for making short-term (60-day) forecasts of the growth and spread of a malignant brain cancer (glioblastoma multiforme) in individual patient cases, where the observations are synthetic magnetic resonance images of a hypothetical tumor. Results: We apply a modern state estimation algorithm (the Local Ensemble Transform Kalman Filter), previously developed for numerical weather prediction, to two different mathematical models of glioblastoma, taking into account likelyn errors in model parameters and measurement uncertainties in magnetic resonance imaging. The filter can accurately shadow the growth of a representative synthetic tumor for 360 days (six 60-day forecast/update cycles) in the presence of a moderate degree of systematic model error and measurement noise. Conclusions: The mathematical methodology described here may prove useful for other modeling efforts in biology and oncology.An accurate forecast system for glioblastoma may prove useful in clinical settings for treatment planning and patient counseling.Reviewers: This article was reviewed by Anthony Almudevar, Tomas Radivoyevitch, and Kristin Swanson (nominated by George Luebeck). http://www.biology-direct.com/content/6/1/64 Eric Kostelich Yang Kuang Joshua McDaniel Nina Moore Nikolay Martirosyan Mark Preul Biology Direct 2011, null:64 2011-12-21T00:00:00Z doi:10.1186/1745-6150-6-64 Predicting human brain tumors State estimation schemes, employed operationally for weather forecasting, can be applied in principle to make useful short-term predictions of the growth and spread of malignant tumors in individual patient cases. /content/figures/1745-6150-6-64-toc.gif Biology Direct 1745-6150 ${item.volume} 64 2011-12-21T00:00:00Z PDF Background: The transition from prokaryotes to eukaryotes was the most radical change in cell organisation since life began, with the largest ever burst of gene duplication and novelty. According to the coevolutionary theory of eukaryote origins, the fundamental innovations were the concerted origins of the endomembrane system and cytoskeleton, subsequently recruited to form the cell nucleus and coevolving mitotic apparatus, with numerous genetic eukaryotic novelties inevitable consequences of this compartmentation and novel DNA segregation mechanism. Physical and mutational mechanisms of origin of the nucleus are seldom considered beyond the long-standing assumption that it involved wrapping pre-existing endomembranes around chromatin. Discussions on the origin of sex typically overlook its association with protozoan entry into dormant walled cysts and the likely simultaneous coevolutionary, not sequential, origin of mitosis and meiosis. Results: I elucidate nuclear and mitotic coevolution, explaining the origins of dicer and small centromeric RNAs for positionally controlling centromeric heterochromatin, and how 27 major features of the cell nucleus evolved in four logical stages, making both mechanisms and selective advantages explicit: two initial stages (origin of 30 nm chromatin fibres, enabling DNA compaction; and firmer attachment of endomembranes to heterochromatin) protected DNA and nascent RNA from shearing by novel molecular motors mediating vesicle transport, division, and cytoplasmic motility. Then octagonal nuclear pore complexes (NPCs) arguably evolved from COPII coated vesicle proteins trapped in clumps by Ran GTPase-mediated cisternal fusion that generated the fenestrated nuclear envelope, preventing lethal complete cisternal fusion, and allowing passive protein and RNA exchange. Finally, plugging NPC lumens by an FG-nucleoporin meshwork and adopting karyopherins for nucleocytoplasmic exchange conferred compartmentation advantages. These successive changes took place in naked growing cells, probably as indirect consequences of the origin of phagotrophy. The first eukaryote had 1-2 cilia and also walled resting cysts; I outline how encystation may have promoted the origin of meiotic sex. I also explain why many alternative ideas are inadequate. Conclusion: Nuclear pore complexes are evolutionary chimaeras of endomembrane- and mitosis-related chromatin-associated proteins. The keys to understanding eukaryogenesis are a proper phylogenetic context and understanding organelle coevolution: how innovations in one cell component caused repercussions on others.ReviewersThis article was reviewed by Anthony Poole, Gáspár Jékely and Eugene Koonin. http://www.biology-direct.com/content/5/1/7 Thomas Cavalier-Smith Biology Direct 2010, null:7 2010-02-04T00:00:00Z doi:10.1186/1745-6150-5-7 /content/figures/1745-6150-5-7-toc.gif Biology Direct 1745-6150 ${item.volume} 7 2010-02-04T00:00:00Z XML Background: This study aims to establish the likely origin of EEJ (Eastern European Jews) by genetic distance analysis of autosomal markers and haplogroups on the X and Y chromosomes and mtDNA. Results: According to the autosomal polymorphisms the investigated Jewish populations do not share a common origin, and EEJ are closer to Italians in particular and to Europeans in general than to the other Jewish populations. The similarity of EEJ to Italians and Europeans is also supported by the X chromosomal haplogroups. In contrast according to the Y-chromosomal haplogroups EEJ are closest to the non-Jewish populations of the Eastern Mediterranean. MtDNA shows a mixed pattern, but overall EEJ are more distant from most populations and hold a marginal rather than a central position. The autosomal genetic distance matrix has a very high correlation (0.789) with geography, whereas the X-chromosomal, Y-chromosomal and mtDNA matrices have a lower correlation (0.540, 0.395 and 0.641 respectively). Conclusions: The close genetic resemblance to Italians accords with the historical presumption that Ashkenazi Jews started their migrations across Europe in Italy and with historical evidence that conversion to Judaism was common in ancient Rome. The reasons for the discrepancy between the biparental markers and the uniparental markers are discussed.ReviewersThis article was reviewed by Damian Labuda (nominated by Jerzy Jurka), Kateryna Makova and Qasim Ayub (nominated by Dan Graur). http://www.biology-direct.com/content/5/1/57 Avshalom Zoossmann-Diskin Biology Direct 2010, null:57 2010-10-06T00:00:00Z doi:10.1186/1745-6150-5-57 /content/figures/1745-6150-5-57-toc.gif Biology Direct 1745-6150 ${item.volume} 57 2010-10-06T00:00:00Z XML Background: Several recent studies have demonstrated the effectiveness of deep sequencing for transcriptome analysis (RNA-seq) in mammals. As RNA-seq becomes more affordable, whole genome transcriptional profiling is likely to become the platform of choice for species with good genomic sequences. As yet, a rigorous analysis methodology has not been developed and we are still in the stages of exploring the features of the data. Results: We investigated the effect of transcript length bias in RNA-seq data using three different published data sets. For standard analyses using aggregated tag counts for each gene, the ability to call differentially expressed genes between samples is strongly associated with the length of the transcript. Conclusion: Transcript length bias for calling differentially expressed genes is a general feature of current protocols for RNA-seq technology. This has implications for the ranking of differentially expressed genes, and in particular may introduce bias in gene set testing for pathway analysis and other multi-gene systems biology analyses.ReviewersThis article was reviewed by Rohan Williams (nominated by Gavin Huttley), Nicole Cloonan (nominated by Mark Ragan) and James Bullard (nominated by Sandrine Dudoit). http://www.biology-direct.com/content/4/1/14 Alicia Oshlack Matthew Wakefield Biology Direct 2009, null:14 2009-04-16T00:00:00Z doi:10.1186/1745-6150-4-14 /content/figures/1745-6150-4-14-toc.gif Biology Direct 1745-6150 ${item.volume} 14 2009-04-16T00:00:00Z XML