Less can be more: RNA-adapters may enhance coding capacity of replicators

It is still not clear how prebiotic replicators evolved towards the complexity found in present day organisms. Within the most realistic scenario for prebiotic evolution, known as the RNA world hypothesis, such complexity has arisen from replicators consisting solely of RNA. Within contemporary life, remarkably many RNAs are involved in modifying other RNAs. In hindsight, such RNA-RNA modification might have helped in alleviating the limits of complexity posed by the information threshold for RNA-only replicators. Here we study the possible role of such self-modification in early evolution, by modeling the evolution of protocells as evolving replicators, which have the opportunity to incorporate these mechanisms as a molecular tool. Evolution is studied towards a set of 25 arbitrary 'functional' structures, while avoiding all other (misfolded) structures, which are considered to be toxic and increase the death-rate of a protocell. The modeled protocells contain a genotype of different RNA-sequences while their phenotype is the ensemble of secondary structures they can potentially produce from these RNA-sequences. One of the secondary structures explicitly codes for a simple sequence-modification tool. This 'RNA-adapter' can block certain positions on other RNA-sequences through antisense base-pairing. The altered sequence can produce an alternative secondary structure, which may or may not be functional. We show that the modifying potential of interacting RNA-sequences enables these protocells to evolve high fitness under high mutation rates. Moreover, our model shows that because of toxicity of misfolded molecules, redundant coding impedes the evolution of self-modification machinery, in effect restraining the evolvability of coding structures. Hence, high mutation rates can actually promote the evolution of complex coding structures by reducing redundant coding. Protocells can successfully use RNA-adapters to modify their genotype-phenotype mapping in order to enhance the coding capacity of their genome and fit more information on smaller sized genomes.     

Aspects of statin prescribing in Norwegian counties with high,average and low statin consumption – an individual-level prescription database study

Background  

A previous study has shown that variations in threshold and intensity (lipid goal attainment) of statins for primary prevention contribute to regional differences in overall consumption of statins in Norway. Our objective was to explore how differences in prevalences of use, dosing characteristics, choice of statin and continuity of therapy in individual patients adds new information to previous results.     

Time-dependent structural transformation analysis to high-level Petri net model with active state transition diagram

Background  

With an accumulation of in silico data obtained by simulating large-scale biological networks, a new interest of research is emerging for elucidating how living organism functions over time in cells.     

The relationship between the error catastrophe, survival of the flattest, and natural selection

Background  

The quasispecies model is a general model of evolution that is generally applicable to replication up to high mutation rates. It predicts that at a sufficiently high mutation rate, quasispecies with higher mutational robustness can displace quasispecies with higher replicative capacity, a phenomenon called "survival of the flattest". In some fitness landscapes it also predicts the existence of a maximum mutation rate, called the error threshold, beyond which the quasispecies enters into error catastrophe, losing its genetic information. The aim of this paper is to study the relationship between survival of the flattest and the transition to error catastrophe, as well as the connection between these concepts and natural selection.     

Genome wide prediction of protein function via a generic knowledge discovery approach based on evidence integration

Background  

The automation of many common molecular biology techniques has resulted in the accumulation of vast quantities of experimental data. One of the major challenges now facing researchers is how to process this data to yield useful information about a biological system (e.g. knowledge of genes and their products, and the biological roles of proteins, their molecular functions, localizations and interaction networks). We present a technique called Global Mapping of Unknown Proteins (GMUP) which uses the Gene Ontology Index to relate diverse sources of experimental data by creation of an abstraction layer of evidence data. This abstraction layer is used as input to a neural network which, once trained, can be used to predict function from the evidence data of unannotated proteins. The method allows us to include almost any experimental data set related to protein function, which incorporates the Gene Ontology, to our evidence data in order to seek relationships between the different sets.     

Association of a novel point mutation in MSH2 gene with familial multiple primary cancers

Background

Multiple primary cancers (MPC) have been identified as two or more cancers without any subordinate relationship that occur either simultaneously or metachronously in the same or different organs of an individual. Lynch syndrome is an autosomal dominant genetic disorder that increases the risk of many types of cancers. Lynch syndrome patients who suffer more than two cancers can also be considered as MPC; patients of this kind provide unique resources to learn how genetic mutation causes MPC in different tissues.

Methods

We performed a whole genome sequencing on blood cells and two tumor samples of a Lynch syndrome patient who was diagnosed with five primary cancers. The mutational landscape of the tumors, including somatic point mutations and copy number alternations, was characterized. We also compared Lynch syndrome with sporadic cancers and proposed a model to illustrate the mutational process by which Lynch syndrome progresses to MPC.

Results

We revealed a novel pathologic mutation on the MSH2 gene (G504 splicing) that associates with Lynch syndrome. Systematical comparison of the mutation landscape revealed that multiple cancers in the proband were evolutionarily independent. Integrative analysis showed that truncating mutations of DNA mismatch repair (MMR) genes were significantly enriched in the patient. A mutation progress model that included germline mutations of MMR genes, double hits of MMR system, mutations in tissue-specific driver genes, and rapid accumulation of additional passenger mutations was proposed to illustrate how MPC occurs in Lynch syndrome patients.

Conclusion

Our findings demonstrate that both germline and somatic alterations are driving forces of carcinogenesis, which may resolve the carcinogenic theory of Lynch syndrome.

     

Quantitative elementary mode analysis of metabolic pathways: the example of yeast glycolysis

Background  

Elementary mode analysis of metabolic pathways has proven to be a valuable tool for assessing the properties and functions of biochemical systems. However, little comprehension of how individual elementary modes are used in real cellular states has been achieved so far. A quantitative measure of fluxes carried by individual elementary modes is of great help to identify dominant metabolic processes, and to understand how these processes are redistributed in biological cells in response to changes in environmental conditions, enzyme kinetics, or chemical concentrations.     

The origin of replicators and reproducers

Replicators are fundamental to the origin of life and evolvability. Their survival depends on the accuracy of replication and the efficiency of growth relative to spontaneous decay. Infrabiological systems are built of two coupled autocatalytic systems, in contrast to minimal living systems that must comprise at least a metabolic subsystem, a hereditary subsystem and a boundary, serving respective functions. Some scenarios prefer to unite all these functions into one primordial system, as illustrated in the lipid world scenario, which is considered as a didactic example in detail. Experimentally produced chemical replicators grow parabolically owing to product inhibition. A selection consequence is survival of everybody. The chromatographized replicator model predicts that such replicators spreading on surfaces can be selected for higher replication rate because double strands are washed away slower than single strands from the surface. Analysis of real ribozymes suggests that the error threshold of replication is less severe by about one order of magnitude than thought previously. Surface-bound dynamics is predicted to play a crucial role also for exponential replicators: unlinked genes belonging to the same genome do not displace each other by competition, and efficient and accurate replicases can spread. The most efficient form of such useful population structure is encapsulation by reproducing vesicles. The stochastic corrector model shows how such a bag of genes can survive, and what the role of chromosome formation and intragenic recombination could be. Prebiotic and early evolution cannot be understood without the models of dynamics.     

Mutation accumulation in <Emphasis Type="Italic">Tetrahymena</Emphasis>

Background  

The rate and fitness effects of mutations are key in understanding the evolution of every species. Traditionally, these parameters are estimated in mutation accumulation experiments where replicate lines are propagated in conditions that allow mutations to randomly accumulate without the purging effect of natural selection. These experiments have been performed with many model organisms but we still lack empirical estimates of the rate and effects of mutation in the protists.     

Acoustic Communication and Sound Degradation: How Do the Individual Signatures of Male and Female Zebra Finch Calls Transmit over Distance?

Background

Assessing the active space of the various types of information encoded by songbirds'' vocalizations is important to address questions related to species ecology (e.g. spacing of individuals), as well as social behavior (e.g. territorial and/or mating strategies). Up to now, most of the previous studies have investigated the degradation of species-specific related information (species identity), and there is a gap of knowledge of how finer-grained information (e.g. individual identity) can transmit through the environment. Here we studied how the individual signature coded in the zebra finch long distance contact call degrades with propagation.

Methodology

We performed sound transmission experiments of zebra finches'' distance calls at various propagation distances. The propagated calls were analyzed using discriminant function analyses on a set of analytical parameters describing separately the spectral and temporal envelopes, as well as on a complete spectrographic representation of the signals.

Results/Conclusion

We found that individual signature is remarkably resistant to propagation as caller identity can be recovered even at distances greater than a hundred meters. Male calls show stronger discriminability at long distances than female calls, and this difference can be explained by the more pronounced frequency modulation found in their calls. In both sexes, individual information is carried redundantly using multiple acoustical features. Interestingly, features providing the highest discrimination at short distances are not the same ones that provide the highest discrimination at long distances.     

Plant traits and ecosystem effects of clonality: a new research agenda

Background

Clonal plants spread laterally by spacers between their ramets (shoot–root units); these spacers can transport and store resources. While much is known about how clonality promotes plant fitness, we know little about how different clonal plants influence ecosystem functions related to carbon, nutrient and water cycling.

Approach

The response–effect trait framework is used to formulate hypotheses about the impact of clonality on ecosystems. Central to this framework is the degree of correspondence between interspecific variation in clonal ‘response traits’ that promote plant fitness and interspecific variation in ‘effect traits’, which define a plant''s potential effect on ecosystem functions. The main example presented to illustrate this concept concerns clonal traits of vascular plant species that determine their lateral extension patterns. In combination with the different degrees of decomposability of litter derived from their spacers, leaves, roots and stems, these clonal traits should determine associated spatial and temporal patterns in soil organic matter accumulation, nutrient availability and water retention.

Conclusions

This review gives some concrete pointers as to how to implement this new research agenda through a combination of (1) standardized screening of predominant species in ecosystems for clonal response traits and for effect traits related to carbon, nutrient and water cycling; (2) analysing the overlap between variation in these response traits and effect traits across species; (3) linking spatial and temporal patterns of clonal species in the field to those for soil properties related to carbon, nutrient and water stocks and dynamics; and (4) studying the effects of biotic interactions and feedbacks between resource heterogeneity and clonality. Linking these to environmental changes may help us to better understand and predict the role of clonal plants in modulating impacts of climate change and human activities on ecosystem functions.     

Prelife catalysts and replicators

Life is based on replication and evolution. But replication cannot be taken for granted. We must ask what there was prior to replication and evolution. How does evolution begin? We have proposed prelife as a generative system that produces information and diversity in the absence of replication. We model prelife as a binary soup of active monomers that form random polymers. ‘Prevolutionary’ dynamics can have mutation and selection prior to replication. Some sequences might have catalytic activity, thereby enhancing the rates of certain prelife reactions. We study the selection criteria for these prelife catalysts. Their catalytic efficiency must be above certain critical values. We find a maintenance threshold and an initiation threshold. The former is a linear function of sequence length, and the latter is an exponential function of sequence length. Therefore, it is extremely hard to select for prelife catalysts that have long sequences. We compare prelife catalysis with a simple model for replication. Assuming fast template-based elongation reactions, we can show that replicators have selection thresholds that are independent of their sequence length. Our calculation demonstrates the efficiency of replication and provides an explanation of why replication was selected over other forms of prelife catalysis.     

Plant Species and Functional Group Combinations Affect Green Roof Ecosystem Functions

Background

Green roofs perform ecosystem services such as summer roof temperature reduction and stormwater capture that directly contribute to lower building energy use and potential economic savings. These services are in turn related to ecosystem functions performed by the vegetation layer such as radiation reflection and transpiration, but little work has examined the role of plant species composition and diversity in improving these functions.

Methodology/Principal Findings

We used a replicated modular extensive (shallow growing- medium) green roof system planted with monocultures or mixtures containing one, three or five life-forms, to quantify two ecosystem services: summer roof cooling and water capture. We also measured the related ecosystem properties/processes of albedo, evapotranspiration, and the mean and temporal variability of aboveground biomass over four months. Mixtures containing three or five life-form groups, simultaneously optimized several green roof ecosystem functions, outperforming monocultures and single life-form groups, but there was much variation in performance depending on which life-forms were present in the three life-form mixtures. Some mixtures outperformed the best monocultures for water capture, evapotranspiration, and an index combining both water capture and temperature reductions. Combinations of tall forbs, grasses and succulents simultaneously optimized a range of ecosystem performance measures, thus the main benefit of including all three groups was not to maximize any single process but to perform a variety of functions well.

Conclusions/Significance

Ecosystem services from green roofs can be improved by planting certain life-form groups in combination, directly contributing to climate change mitigation and adaptation strategies. The strong performance by certain mixtures of life-forms, especially tall forbs, grasses and succulents, warrants further investigation into niche complementarity or facilitation as mechanisms governing biodiversity-ecosystem functioning relationships in green roof ecosystems.     

Time-ordered networks reveal limitations to information flow in ant colonies

Background

An important function of many complex networks is to inhibit or promote the transmission of disease, resources, or information between individuals. However, little is known about how the temporal dynamics of individual-level interactions affect these networks and constrain their function. Ant colonies are a model comparative system for understanding general principles linking individual-level interactions to network-level functions because interactions among individuals enable integration of multiple sources of information to collectively make decisions, and allocate tasks and resources.

Methodology/Findings

Here we show how the temporal and spatial dynamics of such individual interactions provide upper bounds to rates of colony-level information flow in the ant Temnothorax rugatulus. We develop a general framework for analyzing dynamic networks and a mathematical model that predicts how information flow scales with individual mobility and group size.

Conclusions/Significance

Using thousands of time-stamped interactions between uniquely marked ants in four colonies of a range of sizes, we demonstrate that observed maximum rates of information flow are always slower than predicted, and are constrained by regulation of individual mobility and contact rate. By accounting for the ordering and timing of interactions, we can resolve important difficulties with network sampling frequency and duration, enabling a broader understanding of interaction network functioning across systems and scales.     

The tendency to recreate ancestral CG dinucleotides in the human genome

Background  

The CG dinucleotides are known to be deficient in the human genome, due to a high mutation rate from 5-methylated CG to TG and its complementary pair CA. Meanwhile, many cellular functions rely on these CG dinucleotides, such as gene expression controlled by cytosine methylation status. Thus, CG dinucleotides that provide essential functional substrates should be retained in genomes. How these two conflicting processes regarding the fate of CG dinucleotides - i.e., high mutation rate destroying CG dinucleotides, vs. functional processes that require their preservation remains an unsolved question.     

Phenotypic error threshold; additivity and epistasis in RNA evolution

Background  

The error threshold puts a limit on the amount of information maintainable in Darwinian evolution. The error threshold was first formulated in terms of genotypes. However, if a genotype-phenotype map involves redundancy ("mutational neutrality"), the error threshold should be formulated in terms of phenotypes since there is no unique fittest genotype. A previous study formulated the error threshold in terms of phenotypes, and their results showed that a rather low degree of mutational neutrality can increase the error threshold unlimitedly.     

The Genome Reverse Compiler: an explorative annotation tool

Background  

As sequencing costs have decreased, whole genome sequencing has become a viable and integral part of biological laboratory research. However, the tools with which genes can be found and functionally characterized have not been readily adapted to be part of the everyday biological sciences toolkit. Most annotation pipelines remain as a service provided by large institutions or come as an unwieldy conglomerate of independent components, each requiring their own setup and maintenance.     

Quantitative comparison of EST libraries requires compensation for systematic biases in cDNA generation

Background  

Publicly accessible EST libraries contain valuable information that can be utilized for studies of tissue-specific gene expression and processing of individual genes. This information is, however, confounded by multiple systematic effects arising from the procedures used to generate these libraries.     

Purging deleterious mutations under self fertilization: paradoxical recovery in fitness with increasing mutation rate in Caenorhabditis elegans

Background

The accumulation of deleterious mutations can drastically reduce population mean fitness. Self-fertilization is thought to be an effective means of purging deleterious mutations. However, widespread linkage disequilibrium generated and maintained by self-fertilization is predicted to reduce the efficacy of purging when mutations are present at multiple loci.

Methodology/Principal Findings

We tested the ability of self-fertilizing populations to purge deleterious mutations at multiple loci by exposing obligately self-fertilizing populations of Caenorhabditis elegans to a range of elevated mutation rates and found that mutations accumulated, as evidenced by a reduction in mean fitness, in each population. Therefore, purging in obligate selfing populations is overwhelmed by an increase in mutation rate. Surprisingly, we also found that obligate and predominantly self-fertilizing populations exposed to very high mutation rates exhibited consistently greater fitness than those subject to lesser increases in mutation rate, which contradicts the assumption that increases in mutation rate are negatively correlated with fitness. The high levels of genetic linkage inherent in self-fertilization could drive this fitness increase.

Conclusions

Compensatory mutations can be more frequent under high mutation rates and may alleviate a portion of the fitness lost due to the accumulation of deleterious mutations through epistatic interactions with deleterious mutations. The prolonged maintenance of tightly linked compensatory and deleterious mutations facilitated by self-fertilization may be responsible for the fitness increase as linkage disequilibrium between the compensatory and deleterious mutations preserves their epistatic interaction.