The network Laplacian spectral density calculation is critical in many fields, including physics, chemistry, statistics, and mathematics. It is highly computationally intensive, limiting the analysis ...to small networks. Therefore, we present two efficient alternatives: one based on the network’s edges and another on the degrees. The former gives the exact spectral density of locally tree-like networks but requires iterative edge-based message-passing equations. In contrast, the latter obtains an approximation of the spectral density using only the degree distribution. The computational complexities are (|E|log(n)) and (n), respectively, in contrast to (n3) of the diagonalization method, where n is the number of vertices and |E| is the number of edges.
In many eukaryotic genomes only a small fraction of the DNA codes for proteins, but the non-protein coding DNA harbors important genetic elements directing the development and the physiology of the ...organisms, like promoters, enhancers, insulators, and micro-RNA genes. The molecular evolution of these genetic elements is difficult to study because their functional significance is hard to deduce from sequence information alone. Here we propose an approach to the study of the rate of evolution of functional non-coding sequences at a macro-evolutionary scale. We identify functionally important non-coding sequences as Conserved Non-Coding Nucleotide (CNCN) sequences from the comparison of two outgroup species. The CNCN sequences so identified are then compared to their homologous sequences in a pair of ingroup species, and we monitor the degree of modification these sequences suffered in the two ingroup lineages. We propose a method to test for rate differences in the modification of CNCN sequences among the two ingroup lineages, as well as a method to estimate their rate of modification. We apply this method to the full sequences of the HoxA clusters from six gnathostome species: a shark, Heterodontus francisci; a basal ray finned fish, Polypterus senegalus; the amphibian, Xenopus tropicalis; as well as three mammalian species, human, rat and mouse. The results show that the evolutionary rate of CNCN sequences is not distinguishable among the three mammalian lineages, while the Xenopus lineage has a significantly increased rate of evolution. Furthermore the estimates of the rate parameters suggest that in the stem lineage of mammals the rate of CNCN sequence evolution was more than twice the rate observed within the placental amniotes clade, suggesting a high rate of evolution of cis-regulatory elements during the origin of amniotes and mammals. We conclude that the proposed methods can be used for testing hypotheses about the rate and pattern of evolution of putative cis-regulatory elements.
MOLECULAR REPLICATOR DYNAMICS Stadler, Peter F; Stadler, Bärbel M. R
Advances in complex systems,
03/2003, Letnik:
6, Številka:
1
Journal Article
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Template-dependent replication at the molecular level is the basis of reproduction in nature. A detailed understanding of the peculiarities of the chemical reaction kinetics associated with ...replication processes is therefore an indispensible prerequisite for any understanding of evolution at the molecular level. Networks of interacting self-replicating species can give rise to a wealth of different dynamical phenomena, from competitive exclusion to permanent coexistence, from global stability to multi-stability and chaotic dynamics. Nevertheless, there are some general principles that govern their overall behavior. We focus on the question to what extent the dynamics of replication can explain the accumulation of genetic information that eventually leads to the emergence of the first cell and hence the origin of life as we know it. A large class of ligation-based replication systems, which includes the experimentally available model systems for template directed self-replication, is of particular interest because its dynamics bridges the gap between the survival of a single fittest species to the global coexistence of everthing. In this intermediate regime the selection is weak enough to allow the coexistence of genetically unrelated replicators and strong enough to limit the accumulation of disfunctional mutants.
Background
The metabolic architectures of extant organisms share many key pathways such as the citric acid cycle, glycolysis, or the biosynthesis of most amino acids. Several competing hypotheses for ...the evolutionary mechanisms that shape metabolic networks have been discussed in the literature, each of which finds support from comparative analysis of extant genomes. Alternatively, the principles of metabolic evolution can be studied by direct computer simulation. This requires, however, an explicit implementation of all pertinent components: a universe of chemical reactions upon which the metabolism is built, an explicit representation of the enzymes that implement the metabolism, a genetic system that encodes these enzymes, and a fitness function that can be selected for.
Results
We describe here a simulation environment that implements all these components in a simplified way so that large-scale evolutionary studies are feasible. We employ an artificial chemistry that views chemical reactions as graph rewriting operations and utilizes a toy-version of quantum chemistry to derive thermodynamic parameters. Minimalist organisms with simple string-encoded genomes produce model ribozymes whose catalytic activity is determined by an
ad hoc
mapping between their secondary structure and the transition state graphs that they stabilize. Fitness is computed utilizing the ideas of metabolic flux analysis. We present an implementation of the complete system and first simulation results.
Conclusions
The simulation system presented here allows coherent investigations into the evolutionary mechanisms of the first steps of metabolic evolution using a self-consistent toy universe.
This editorial announces Algorithms for Molecular Biology, a new online open access journal published by BioMed Central. By launching the first open access journal on algorithmic bioinformatics, we ...provide a forum for fast publication of high-quality research articles in this rapidly evolving field. Our journal will publish thoroughly peer-reviewed papers without length limitations covering all aspects of algorithmic data analysis in computational biology. Publications in Algorithms for Molecular Biology are easy to find, highly visible and tracked by organisations such as PubMed. An established online submission system makes a fast reviewing procedure possible and enables us to publish accepted papers without delay. All articles published in our journal are permanently archived by PubMed Central and other scientific archives. We are looking forward to receiving your contributions.
A class of autocatalytic reaction networks based on template-dependent ligation and higher-order catalysis is analysed. Apart from an irreversible ligation reaction we consider only reversible ...aggregation steps that provide a realistic description of molecular recognition. The overall dynamics can be understood by means of replicator equations with highly non-linear interaction functions. The dynamics depends crucially on the total concentration c0of replicating material. For small c0, in the hyperbolic growth regime, we recover the familiar dynamics of second-order replicator equations with its wealth of complex dynamics ranging from multi-stability to periodic and strange attractors as well as to heteroclinic orbits. For large c0, in the parabolic growth regime, product inhibition becomes dominating and we observe a single globally stable equilibrium tantamount to permanent coexistence. In an intermediate parameter range we sometimes observe a behavior that is reminiscent of ‘survival of the fittest’. Independently replicating species (Schlögl’s model) and the hypercycle are discussed in detail.
MicroRNA are well-established players in post-transcriptional gene regulation. However, information on the effects of microRNA deregulation mainly relies on bioinformatic prediction of potential ...targets, whereas proof of the direct physical microRNA/target messenger RNA interaction is mostly lacking. Within the International Cancer Genome Consortium Project "Determining Molecular Mechanisms in Malignant Lymphoma by Sequencing", we performed miRnome sequencing from 16 Burkitt lymphomas, 19 diffuse large B-cell lymphomas, and 21 follicular lymphomas. Twenty-two miRNA separated Burkitt lymphomas from diffuse large B-cell lymphomas/follicular lymphomas, of which 13 have shown regulation by MYC. Moreover, we found expression of three hitherto unreported microRNA. Additionally, we detected recurrent mutations of hsa-miR-142 in diffuse large B-cell lymphomas and follicular lymphomas, and editing of the hsa-miR-376 cluster, providing evidence for microRNA editing in lymphomagenesis. To interrogate the direct physical interactions of microRNA with messenger RNA, we performed Argonaute-2 photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation experiments. MicroRNA directly targeted 208 messsenger RNA in the Burkitt lymphomas and 328 messenger RNA in the non-Burkitt lymphoma models. This integrative analysis discovered several regulatory pathways of relevance in lymphomagenesis including Ras, PI3K-Akt and MAPK signaling pathways, also recurrently deregulated in lymphomas by mutations. Our dataset reveals that messenger RNA deregulation through microRNA is a highly relevant mechanism in lymphomagenesis.
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