Spontaneous chiral symmetry breaking in early molecular networks

Background  

An important facet of early biological evolution is the selection of chiral enantiomers for molecules such as amino acids and sugars. The origin of this symmetry breaking is a long-standing question in molecular evolution. Previous models addressing this question include particular kinetic properties such as autocatalysis or negative cross catalysis.     

A protein evolution model with independent sites that reproduces site-specific amino acid distributions from the Protein Data Bank

Background  

Since thermodynamic stability is a global property of proteins that has to be conserved during evolution, the selective pressure at a given site of a protein sequence depends on the amino acids present at other sites. However, models of molecular evolution that aim at reconstructing the evolutionary history of macromolecules become computationally intractable if such correlations between sites are explicitly taken into account.     

Evolution favors protein mutational robustness in sufficiently large populations

Background  

An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties.     

Network analysis of metabolic enzyme evolution in <Emphasis Type="Italic">Escherichia coli</Emphasis>

Background  

The two most common models for the evolution of metabolism are the patchwork evolution model, where enzymes are thought to diverge from broad to narrow substrate specificity, and the retrograde evolution model, according to which enzymes evolve in response to substrate depletion. Analysis of the distribution of homologous enzyme pairs in the metabolic network can shed light on the respective importance of the two models. We here investigate the evolution of the metabolism in E. coli viewed as a single network using EcoCyc.     

SIMPROT: Using an empirically determined indel distribution in simulations of protein evolution

Background  

General protein evolution models help determine the baseline expectations for the evolution of sequences, and they have been extensively useful in sequence analysis and for the computer simulation of artificial sequence data sets.     

Empirical codon substitution matrix

Background  

Codon substitution probabilities are used in many types of molecular evolution studies such as determining Ka/Ks ratios, creating ancestral DNA sequences or aligning coding DNA. Until the recent dramatic increase in genomic data enabled construction of empirical matrices, researchers relied on parameterized models of codon evolution. Here we present the first empirical codon substitution matrix entirely built from alignments of coding sequences from vertebrate DNA and thus provide an alternative to parameterized models of codon evolution.     

Parasite-mediated disruptive selection in a natural <Emphasis Type="Italic">Daphnia</Emphasis> population

Background  

A mismatch has emerged between models and data of host-parasite evolution. Theory readily predicts that parasites can promote host diversity through mechanisms such as disruptive selection. Yet, despite these predictions, empirical evidence for parasite-mediated increases in host diversity remains surprisingly scant.     

Comparative analysis of protein coding sequences from human,mouse and the domesticated pig

Background  

The availability of abundant sequence data from key model organisms has made large scale studies of molecular evolution an exciting possibility. Here we use full length cDNA alignments comprising more than 700,000 nucleotides from human, mouse, pig and the Japanese pufferfish Fugu rubrices in order to investigate 1) the relationships between three major lineages of mammals: rodents, artiodactyls and primates, and 2) the rate of evolution and the occurrence of positive Darwinian selection using codon based models of sequence evolution.     

A system for studying evolution of life-like virtual organisms

Background  

Fitness landscapes, the dependences of fitness on the genotype, are of critical importance for the evolution of living beings. Unfortunately, fitness landscapes that are relevant to the evolution of complex biological functions are very poorly known. As a result, the existing theory of evolution is mostly based on postulated fitness landscapes, which diminishes its usefulness. Attempts to deduce fitness landscapes from models of actual biological processes led, so far, to only limited success.     

Pitfalls of the most commonly used models of context dependent substitution

Background  

Neighboring nucleotides exert a striking influence on mutation, with the hypermutability of CpG dinucleotides in many genomes being an exemplar. Among the approaches employed to measure the relative importance of sequence neighbors on molecular evolution have been continuous-time Markov process models for substitutions that treat sequences as a series of independent tuples. The most widely used examples are the codon substitution models. We evaluated the suitability of derivatives of the nucleotide frequency weighted (hereafter NF) and tuple frequency weighted (hereafter TF) models for measuring sequence context dependent substitution. Critical properties we address are their relationships to an independent nucleotide process and the robustness of parameter estimation to changes in sequence composition. We then consider the impact on inference concerning dinucleotide substitution processes from application of these two forms to intron sequence alignments from primates.     

Post-duplication charge evolution of phosphoglucose isomerases in teleost fishes through weak selection on many amino acid sites

Background  

The partitioning of ancestral functions among duplicated genes by neutral evolution, or subfunctionalization, has been considered the primary process for the evolution of novel proteins (neofunctionalization). Nonetheless, how a subfunctionalized protein can evolve into a more adaptive protein is poorly understood, mainly due to the limitations of current analytical methods, which can detect only strong selection for amino acid substitutions involved in adaptive molecular evolution. In this study, we employed a comparative evolutionary approach to this question, focusing on differences in the structural properties of a protein, specifically the electric charge, encoded by fish-specific duplicated phosphoglucose isomerase (Pgi) genes.     

Gene family evolution: an in-depth theoretical and simulation analysis of non-linear birth-death-innovation models

Background  

The size distribution of gene families in a broad range of genomes is well approximated by a generalized Pareto function. Evolution of ensembles of gene families can be described with Birth, Death, and Innovation Models (BDIMs). Analysis of the properties of different versions of BDIMs has the potential of revealing important features of genome evolution.     

The globin gene family of the cephalochordate amphioxus: implications for chordate globin evolution

Background  

The lancelet amphioxus (Cephalochordata) is a close relative of vertebrates and thus may enhance our understanding of vertebrate gene and genome evolution. In this context, the globins are one of the best studied models for gene family evolution. Previous biochemical studies have demonstrated the presence of an intracellular globin in notochord tissue and myotome of amphioxus, but the corresponding gene has not yet been identified. Genomic resources of Branchiostoma floridae now facilitate the identification, experimental confirmation and molecular evolutionary analysis of its globin gene repertoire.     

Elastic,not plastic species: Frozen plasticity theory and the origin of adaptive evolution in sexually reproducing organisms

Background  

Darwin's evolutionary theory could easily explain the evolution of adaptive traits (organs and behavioral patterns) in asexual but not in sexual organisms. Two models, the selfish gene theory and frozen plasticity theory were suggested to explain evolution of adaptive traits in sexual organisms in past 30 years.     

Is the development of falciparum malaria in the human host limited by the availability of uninfected erythrocytes?

Background  

The development and propagation of malaria parasites in their vertebrate host is a complex process in which various host and parasite factors are involved. Sometimes the evolution of parasitaemia seems to be quelled by parasite load. In order to understand the typical dynamics of evolution of parasitaemia, various mathematical models have been developed. The basic premise ingrained in most models is that the availability of uninfected red blood cells (RBC) in which the parasite develops is a limiting factor in the propagation of the parasite population.     

Integrating protein structures and precomputed genealogies in the Magnum database: Examples with cellular retinoid binding proteins

Background  

When accurate models for the divergent evolution of protein sequences are integrated with complementary biological information, such as folded protein structures, analyses of the combined data often lead to new hypotheses about molecular physiology. This represents an excellent example of how bioinformatics can be used to guide experimental research. However, progress in this direction has been slowed by the lack of a publicly available resource suitable for general use.     

Evolution and origin of merlin,the product of the <Emphasis Type="Italic">Neurofibromatosis type 2</Emphasis> (<Emphasis Type="Italic">NF2</Emphasis>) tumor-suppressor gene

Background  

Merlin, the product of the Neurofibromatosis type 2 (NF2) tumor suppressor gene, belongs to the ezrin-radixin-moesin (ERM) subgroup of the protein 4.1 superfamily, which links cell surface glycoproteins to the actin cytoskeleton. While merlin's functional activity has been examined in mammalian and Drosophila models, little is understood about its evolution, diversity, and overall distribution among different taxa.     

Analysis on the reconstruction accuracy of the Fitch method for inferring ancestral states

Background  

As one of the most widely used parsimony methods for ancestral reconstruction, the Fitch method minimizes the total number of hypothetical substitutions along all branches of a tree to explain the evolution of a character. Due to the extensive usage of this method, it has become a scientific endeavor in recent years to study the reconstruction accuracies of the Fitch method. However, most studies are restricted to 2-state evolutionary models and a study for higher-state models is needed since DNA sequences take the format of 4-state series and protein sequences even have 20 states.     

Computing and visually analyzing mutual information in molecular co-evolution

Background  

Selective pressure in molecular evolution leads to uneven distributions of amino acids and nucleotides. In fact one observes correlations among such constituents due to a large number of biophysical mechanisms (folding properties, electrostatics, ...). To quantify these correlations the mutual information -after proper normalization - has proven most effective. The challenge is to navigate the large amount of data, which in a study for a typical protein cannot simply be plotted.