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We suggest simulating evolution of complex organisms using a model constrained solely by the requirement of robustness in its expression patterns. This scenario is illustrated by evolving discrete logical networks with epigenetic properties. Evidence for dynamical features in the evolved networks is found that can be related to biological observables.
The removal of intervening sequences from pre-mRNA is an important step in gene regulation. Pre-mRNA processing takes place within the spliceosome, a dynamic structure composed of small nuclear RNA (snRNA) and proteins. The function of the spliceosome is currently being studied in many eukaryotic systems including mammal and yeast. Here we review pre-mRNA splicing in fission yeast and man and propose that spliceosomal structure and function has been evolutionarily conserved between the two organisms.
We develop a cytonuclear framework for tetraploid populations in which a diallelic nuclear marker exhibits tetrasomic inheritance. This system requires two separate parameterizations, with six cytonuclear disequilibria (nonrandom associations) in tetraploid individuals and four in their diploid gametes. Double reduction during meiosis adds further complexity by causing gametic output to vary with the distance of the nuclear locus from the centromere. We derive and analyze dynamical solutions for the disequilibria under generalized mixed mating, with any combination of apomixis, selfing, and outcrossing, with and without double reduction. As in comparable diploid systems, all disequilibria ultimately decay to zero, unless nuclear and cytoplasmic alleles are nonrandomly associated and outcrossing is absent, in which case permanent associations result. Selfing and apomixis retard the decay of disequilibria (or approach to equilibrium), and often to the same extent. In contrast, double reduction can accelerate the loss of tetraploid cytonuclear associations, but only negligibly in hybrid zones, and this loss is never faster than in diploids. Only in the absence of allelic associations or outcrossing is the asymptotic approach to equilibrium differentially affected by apomixis and selfing or slower under tetrasomic than disomic inheritance. To facilitate empirical applications, we also examine tetraploid hybrid zone dynamics and offer practical guidelines for experimental design and data analysis, showing how the consequences of the mating system alone provide a valuable baseline for drawing evolutionary inferences from the observed patterns of cytonuclear associations.
One of the consequences of viral quasispecies dynamics is the presence, in the mutant spectrum, of minority memory genomes that reflect those variants that were dominant at an earlier phase of the same evolutionary lineage. Replicative and cellular (or anatomical) contributions to quasispecies memory were previously defined during intrahost evolution of human immunodeficiency virus type 1 (HIV-1) [Briones, C., Domingo, E., Molina-París, C., 2003. Memory in retroviral quasispecies: experimental evidence and theoretical model for human immunodeficiency virus. J. Mol. Biol. 331, 213-229.]. However, the effects of replicative memory regarding virus evolution in vivo have not been investigated. Here we document that a multidrug-resistant (MDR) HIV-1, present at memory level, determined the ensuing evolution of the virus in an infected patient. Nucleotide sequencing and detailed phylogenetic analyses of sequential viral populations and individual molecular clones evidenced that the progeny of a minority MDR genome during a treatment interruption contributed the dominant genomes when an antiretroviral treatment was restored. An extension of a mathematical model of establishment and maintenance of memory, based on quasispecies theory, supports the experimental data. Therefore a replicative memory subpopulation, not detectable in a consensus nucleotide sequence, affected decisively subsequent states of viral evolution in vivo.
Understanding how DNA sequence variations impact human health through a hierarchy of biochemical and physiological systems is expected to improve the diagnosis, prevention, and treatment of common, complex human diseases. We have previously developed a hierarchical dynamic systems approach based on Petri nets for generating biochemical network models that are consistent with genetic models of disease susceptibility. This modeling approach uses an evolutionary computation approach called grammatical evolution as a search strategy for optimal Petri net models. We have previously demonstrated that this approach routinely identifies biochemical network models that are consistent with a variety of genetic models in which disease susceptibility is determined by nonlinear interactions between two or more DNA sequence variations. We review here this approach and then discuss how it can be used to model biochemical and metabolic data in the context of genetic studies of human disease susceptibility.
Understanding how DNA sequence variations impact human health through a hierarchy of biochemical and physiological systems is expected to improve the diagnosis, prevention, and treatment of common, complex human diseases. We have previously developed a hierarchical dynamic systems approach based on Petri nets for generating biochemical network models that are consistent with genetic models of disease susceptibility. This modeling approach uses an evolutionary computation approach called grammatical evolution as a search strategy for optimal Petri net models. We have previously demonstrated that this approach routinely identifies biochemical network models that are consistent with a variety of genetic models in which disease susceptibility is determined by nonlinear interactions between two DNA sequence variations. In the present study, we evaluate whether the Petri net approach is capable of identifying biochemical networks that are consistent with disease susceptibility due to higher order nonlinear interactions between three DNA sequence variations. The results indicate that our model-building approach is capable of routinely identifying good, but not perfect, Petri net models. Ideas for improving the algorithm for this high-dimensional problem are presented.
In the aim to assess whether the tri-repeat shortage reported in vertebrates affects specific motifs, such as those causing neuromuscular diseases in man, we detected approximate di-, tri- and tetra-repeats (STR) longer than 25 bases in human chromosomes 21 and 22, and in some model organisms (M. musculus, D. melanogaster, C. elegans, A. thaliana and S. cerevisiae). We found that overall STR are more represented in mouse and in man than in the other organisms. However, tri-repeats are less represented than di- and tetra- in man and mouse, but show intermediate values between di- and tetra- in the other organisms. In man, ACG shows the lowest both frequency and coverage, ATC the highest coverage and AAT the highest frequency. In general, coverage and frequency of tri-repeats are linearly related, except for ACC, ATC, AAG, AGG motifs in man and AAG, AGG in mouse, which exhibit unexpectedly long repeats. Often their copy numbers exceed that found responsible for the dynamic mutations, set at around 40. The shortage in frequency and coverage of tri- vs. di- and tetra-repeats observed in man and mouse can be ascribed to a subset of the remaining tri-repeat motifs, but among them those recognized as dynamically mutable (AAG, AGC and CCG) are not the least represented. Possible constraints in tri-repeat expansion seem to be structural and conserved along the evolutionary scale: a motif-specific relaxation of the relevant controls may be responsible for the occasional expansions found in mouse and man.
A prominent feature of comparative life histories in fish (and other indeterminate growers) is the approximate invariance across species of certain dimensionless numbers made up from reproductive and timing variables. The two best known are the age at maturity (alpha) divided by the average adult lifespan (E), and the proportion of a body mass given to reproduction per year (c) multiplied by E. This article uses evolutionary life-history theory for nongrowing populations to predict the numeric value of these numbers for fish and lizards, with several new implications for the dynamics of ontogenetic development.
Models of evolutionary processes postulate that new alleles appear in populations through random spontaneous mutation. Alleles that confer a competitive advantage in particular environments are selected and populations can be taken over by individuals expressing these advantageous mutations. We have studied the evolutionary process by using Escherichia coli cultures incubated for prolonged periods of time in stationary phase. The populations of surviving cells were shown to be highly dynamic, even after many months of incubation. Evolution proceeded along different paths even when the initial conditions were identical. As cultures aged, the takeovers by fitter mutants were incomplete, resulting in the coexistence of multiple mutant forms and increased microbial diversity. Thus, the study of bacterial populations in stationary phase provides a model system for understanding the evolution of diversity in natural populations.
Photosynthetic microbial mat communities were obtained from marine hypersaline saltern ponds, maintained in a greenhouse facility, and examined for the effects of salinity variations. Because these microbial mats are considered to be useful analogs of ancient marine communities, they offer insights about evolutionary events during the >3 billion year time interval wherein mats co-evolved with Earth's lithosphere and atmosphere. Although photosynthetic mats can be highly dynamic and exhibit extremely high activity, the mats in the present study have been maintained for >1 year with relatively minor changes. The major groups of microorganisms, as assayed using microscopic, genetic, and biomarker methodologies, are essentially the same as those in the original field samples. Field and greenhouse mats were similar with respect to rates of exchange of oxygen and dissolved inorganic carbon across the mat-water interface, both during the day and at night. Field and greenhouse mats exhibited similar rates of efflux of methane and hydrogen. Manipulations of salinity in the water overlying the mats produced changes in the community that strongly resemble those observed in the field. A collaboratory testbed and an array of automated features are being developed to support remote scientific experimentation with the assistance of intelligent software agents. This facility will permit teams of investigators the opportunity to explore ancient environmental conditions that are rare or absent today but that might have influenced the early evolution of these photosynthetic ecosystems.
MOTIVATION: The classical duplication episode clustering (EC) model introduced by Guigó et al. in the 1990s provides a foundational approach for inferring genomic duplication events crucial to understanding genome evolution. This model clusters single gene duplications from a collection of gene trees at locations in the species tree to minimize the total number of such locations, called duplication episodes. However, it does not capture reticulate evolutionary histories. RESULTS: Here, we introduce NetEC, a novel extension of this problem to phylogenetic networks. To solve NetEC, we first develop a polynomial-time dynamic programming (DP) algorithm for testing whether a given set of network nodes can serve as episode locations. We then propose a main inference algorithm that utilizes this DP component to optimize the episode count; while the feasibility test runs in polynomial time, the full optimization has exponential worst-case complexity, and an optional heuristic mode is provided for larger instances. We also propose an extended episode analysis procedure that identifies additional genomic duplication candidates below reticulation nodes, complementing the main algorithm by resolving potential upward clustering of duplications induced by reticulation. We evaluate our method on simulated data and on an empirical Pandanales dataset comprising over 29 000 gene trees, demonstrating exact and accurate inference of genomic duplication events even in the presence of multiple reticulations. AVAILABILITY AND IMPLEMENTATION: All experiments were conducted using the NetEC tool (https://github.com/ppgorecki/netec), with all input data, scripts, and parameter settings for reproduction available in the same repository.
The effect of linkage and epistasis on the evolution of the sex-ratio is studied in a symmetric two-locus model of autosomal sex determination closely related to the symmetric viability model of R. C. Lewontin and K. Kojima. R. A. Fisher's expectation of an even sex ratio for autosomal sex determination by a single gene governs the dynamics when the loci are tightly linked. However, recombination may preclude optimization of the sex ratio just as occurs in viability selection models. Many of the evolutionary phenomena known for the symmetric viability model also occur here. In addition, we exhibit a series of new phenomena related to the presence of surfaces of even sex ratio.
Epidemic preparedness depends on tracking microbial evolution that drives shifts in ecological behaviors such as disease emergence. However, the genetic constraints mediating microbial emergence for generalist and specialist behaviors remain poorly described. Here, we addressed this question by combining comparative and functional genomics with phylogeny-based evolutionary analyses of the cereal pathogen Xanthomonas translucens. We show that a generalist X. translucens subgroup arose from a specialist ancestor, and the loss of a single effector gene, xopAL1, contributed to the generalist host expansion by promoting host jump from barley to wheat. Deleting barley-specialist X. translucens xopAL1 recapitulated the host jump to wheat and demonstrates risk across each globally distributed genetic lineage. However, this niche expansion via XopAL1 loss incurs a significant fitness cost to colonize barley. Moreover, the specialist lineage gained an additional effector gene, xopAJ, which enhanced virulence on barley while restricting oat infection, thereby reinforcing niche specialization. We further conducted transcriptomic analysis of wheat and determined that XopAL1 triggers a defense response that involves the reduction of photosynthetic processes. Our work provides an experimentally validated evolutionary framework to understand mechanisms of intergenera host jump. Overall, we demonstrate that single events of gene loss and gain shape ecological behaviors by creating a dynamic trade-off between niche breadth and specialization.
One of the key problems in motor control is mastering or reducing the number of degrees of freedom (DOFs) through coordination. This problem is especially prominent with hyper-redundant limbs such as the extremely flexible arm of the octopus. Several strategies for simplifying these control problems have been suggested for human point-to-point arm movements. Despite the evolutionary gap and morphological differences, humans and octopuses evolved similar strategies when fetching food to the mouth. To achieve this precise point-to-point-task, octopus arms generate a quasi-articulated structure based on three dynamic joints. A rotational movement around these joints brings the object to the mouth . Here, we describe a peripheral neural mechanism-two waves of muscle activation propagate toward each other, and their collision point sets the medial-joint location. This is a remarkably simple mechanism for adjusting the length of the segments according to where the object is grasped. Furthermore, similar to certain human arm movements, kinematic invariants were observed at the joint level rather than at the end-effector level, suggesting intrinsic control coordination. The evolutionary convergence to similar geometrical and kinematic features suggests that a kinematically constrained articulated limb controlled at the level of joint space is the optimal solution for precise point-to-point movements.
Population dynamics across a mortality gradient at an ecological margin are investigated using a novel modeling approach that allows direct comparison of stochastic spatially explicit simulation results with deterministic mean field models. The results show that demographic stochasticity has a large effect at population margins such that density profiles fall off more sharply than predicted by mean field models. Substantial spatial structure emerges at the margin, and spatial correlations (measured parallel to the margin) exhibit a sharp maximum in the tail of the density profile, indicating that spatial substructuring is greatest at an intermediate point across the ecological gradient. Such substructuring may have a substantial impact on Allee effects and evolutionary processes in marginal populations.
A simple model has been used to describe metapopulation dynamics, the spread of an infectious disease, and the dynamics of transposable elements (TEs). This suggests underlying common dynamics despite the different nature of the systems. Eradication thresholds are derived from the common model and they are interpreted for each system. TEs have been viewed as intragenomic parasites. Thus, some ideas derived from epidemiology, and in particular the existence of such eradication thresholds, can be used to explain some evolutionary puzzles such as the strange distribution of TE families within the phylogeny of host species.
A ribosomal frameshift is required for the synthesis of an essential component of the yeast telomerase pathway; this and other findings on telomerases from many species raise interesting questions regarding the evolutionary relationship between telomerases and retrotransposons lacking long terminal repeats.
The hypervariable region 1 (HVR-1) of the putative envelope encoding E2 region of hepatitis C virus (HCV) RNA was analyzed in sequential samples from three patients with acute type C hepatitis infected from different sources to address (i) the dynamics of intrahost HCV variability during the primary infection and (ii) the role of host selective pressure in driving viral genetic evolution. HVR-1 sequences from 20 clones per each point in time were analyzed after amplification, cloning, and purification of plasmid DNA from single colonies of transformed cells. The intrasample evolutionary analysis (nonsynonymous mutations per nonsynonymous site [Ka], synonymous mutations per synonymous site [Ks], Ka/Ks ratio, and genetic distances [gd]) documented low gd in early samples (ranging from 2. 11 to 7.79%) and a further decrease after seroconversion (from 0 to 4.80%), suggesting that primary HCV infection is an oligoclonal event, and found different levels and dynamics of host pressure in the three cases. The intersample analysis (pairwise comparisons of intrapatient sequences; rKa, rKs, rKa/rKs ratio, and gd) confirmed the individual features of HCV genetic evolution in the three subjects and pointed to the relative contribution of either neutral evolution or selective forces in driving viral variability, documenting that adaptation of HCV for persistence in vivo follows different routes, probably representing the molecular counterpart of the viral fitness for individual environments.