Statistical distributions of optimal global alignment scores of random protein sequences

BACKGROUND: The inference of homology from statistically significant sequence similarity is a central issue in sequence alignments. So far the statistical distribution function underlying the optimal global alignments has not been completely determined. RESULTS: In this study, random and real but unrelated sequences prepared in six different ways were selected as reference datasets to obtain their respective statistical distributions of global alignment scores. All alignments were carried out with the Needleman-Wunsch algorithm and optimal scores were fitted to the Gumbel, normal and gamma distributions respectively. The three-parameter gamma distribution performs the best as the theoretical distribution function of global alignment scores, as it agrees perfectly well with the distribution of alignment scores. The normal distribution also agrees well with the score distribution frequencies when the shape parameter of the gamma distribution is sufficiently large, for this is the scenario when the normal distribution can be viewed as an approximation of the gamma distribution. CONCLUSION: We have shown that the optimal global alignment scores of random protein sequences fit the three-parameter gamma distribution function. This would be useful for the inference of homology between sequences whose relationship is unknown, through the evaluation of gamma distribution significance between sequences

Patterns of nucleotides that flank substitutions in human orthologous genes

<p>Abstract</p> <p>Background</p> <p>Sequence context is an important aspect of base mutagenesis, and three-base periodicity is an intrinsic property of coding sequences. However, how three-base periodicity is influenced in the vicinity of substitutions is still unclear. The effect of context on mutagenesis should be revealed in the usage of nucleotides that flank substitutions. Relative entropy (also known as Kullback-Leibler divergence) is useful for finding unusual patterns in biological sequences.</p> <p>Results</p> <p>Using relative entropy, we visualized the periodic patterns in the context of substitutions in human orthologous genes. Neighbouring patterns differed both among substitution categories and within a category that occurred at three codon positions. Transition tended to occur in periodic sequences relative to transversion. Periodic signals were stronger in a set of flanking sequences of substitutions that occurred at the third-codon positions than in those that occurred at the first- or second-codon positions. To determine how the three-base periodicity was affected near the substitution sites, we fitted a sine model to the values of the relative entropy. A sine of period equal to 3 is a good approximation for the three-base periodicity at sites not in close vicinity to some substitutions. These periods were interrupted near the substitution site and then reappeared away from substitutions. A comparative analysis between the native and codon-shuffled datasets suggested that the codon usage frequency was not the sole origin of the three-base periodicity, implying that the native order of codons also played an important role in this periodicity. Synonymous codon shuffling revealed that synonymous codon usage bias was one of the factors responsible for the observed three-base periodicity.</p> <p>Conclusions</p> <p>Our results offer an efficient way to illustrate unusual periodic patterns in the context of substitutions and provide further insight into the origin of three-base periodicity. This periodicity is a result of the native codon order in the reading frame. The length of the period equal to 3 is caused by the usage bias of nucleotides in synonymous codons. The periodic features in nucleotides surrounding substitutions aid in further understanding genetic variation and nucleotide mutagenesis.</p

Impacts of mutation effects and population size on mutation rate in asexual populations: a simulation study

<p>Abstract</p> <p>Background</p> <p>In any natural population, mutation is the primary source of genetic variation required for evolutionary novelty and adaptation. Nevertheless, most mutations, especially those with phenotypic effects, are harmful and are consequently removed by natural selection. For this reason, under natural selection, an organism will evolve to a lower mutation rate. Overall, the action of natural selection on mutation rate is related to population size and mutation effects. Although theoretical work has intensively investigated the relationship between natural selection and mutation rate, most of these studies have focused on individual competition within a population, rather than on competition among populations. The aim of the present study was to use computer simulations to investigate how natural selection adjusts mutation rate among asexually reproducing subpopulations with different mutation rates.</p> <p>Results</p> <p>The competition results for the different subpopulations showed that a population could evolve to an "optimum" mutation rate during long-term evolution, and that this rate was modulated by both population size and mutation effects. A larger population could evolve to a higher optimum mutation rate than could a smaller population. The optimum mutation rate depended on both the fraction and the effects of beneficial mutations, rather than on the effects of deleterious ones. The optimum mutation rate increased with either the fraction or the effects of beneficial mutations. When strongly favored mutations appeared, the optimum mutation rate was elevated to a much higher level. The competition time among the subpopulations also substantially shortened.</p> <p>Conclusions</p> <p>Competition at the population level revealed that the evolution of the mutation rate in asexual populations was determined by both population size and mutation effects. The most striking finding was that beneficial mutations, rather than deleterious mutations, were the leading force that modulated the optimum mutation rate. The initial configuration of the population appeared to have no effect on these conclusions, confirming the robustness of the simulation method developed in the present study. These findings might further explain the lower mutation rates observed in most asexual organisms, as well as the higher mutation rates in some viruses.</p

Patterns of Insertion and Deletion in Mammalian Genomes

Nucleotide insertions and deletions (indels) are responsible for gaps in the sequence alignments. Indel is one of the major sources of evolutionary change at the molecular level. We have examined the patterns of insertions and deletions in the 19 mammalian genomes, and found that deletion events are more common than insertions in the mammalian genomes. Both the number of insertions and deletions decrease rapidly when the gap length increases and single nucleotide indel is the most frequent in all indel events. The frequencies of both insertions and deletions can be described well by power law

The Influence of Deleterious Mutations on Adaptation in Asexual Populations

We study the dynamics of adaptation in asexual populations that undergo both beneficial and deleterious mutations. In particular, how the deleterious mutations affect the fixation of beneficial mutations was investigated. Using extensive Monte Carlo simulations, we find that in the “strong-selection weak mutation (SSWM)” regime or in the “clonal interference (CI)” regime, deleterious mutations rarely influence the distribution of “selection coefficients of the fixed mutations (SCFM)”; while in the “multiple mutations” regime, the accumulation of deleterious mutations would lead to a decrease in fitness significantly. We conclude that the effects of deleterious mutations on adaptation depend largely on the supply of beneficial mutations. And interestingly, the lowest adaptation rate occurs for a moderate value of selection coefficient of deleterious mutations

Rapid Identification of Major QTLS Associated With Near- Freezing Temperature Tolerance in Saccharomyces cerevisiae

Temperatures had a strong effect on many life history traits, including growth, development and reproduction. At near-freezing temperatures (0–4°C), yeast cells could trigger series of biochemical reactions to respond and adapt to the stress, protect them against sever cold and freeze injury. Different Saccharomyces cerevisiae strains vary greatly in their ability to grow at near-freezing temperatures. However, the molecular mechanisms that allow yeast cells to sustain this response are not yet fully understood and the genetic basis of tolerance and sensitivity to near-freeze stress remains unclear. Uncovering the genetic determinants of this trait is, therefore, of is of significant interest. In order to investigate the genetic basis that underlies near-freezing temperature tolerance in S. cerevisiae, we mapped the major quantitative trait loci (QTLs) using bulk segregant analysis (BSA) in the F2 segregant population of two Chinese indigenous S. cerevisiae strains with divergent tolerance capability at 4°C. By genome-wide comparison of single-nucleotide polymorphism (SNP) profiles between two bulks of segregants with high and low tolerance to near-freezing temperature, a hot region located on chromosome IV was identified tightly associated with the near-freezing temperature tolerance. The Reciprocal hemizygosity analysis (RHA) and gene deletion was used to validate the genes involved in the trait, showed that the gene NAT1 plays a role in the near-freezing temperature tolerance. This study improved our understanding of the genetic basis of the variability of near-freezing temperature tolerance in yeasts. The superior allele identified could be used to genetically improve the near-freezing stress adaptation of industrial yeast strains

Tunable topological phase transition in soft Rayleigh beam system with imperfect interfaces

Acoustic metamaterials, particularly the topological insulators, exhibit exceptional wave characteristics that have sparked considerable research interest. The study of imperfect interfaces affect is of significant importance for the modeling of wave propagation behavior in topological insulators. This paper models a soft Rayleigh beam system with imperfect interfaces, and investigates its topological phase transition process tuned by mechanical loadings. The model reveals that the topological phase transition process can be observed by modifying the distance between imperfect interfaces in the system. When a uniaxial stretch is applied, the topological phase transition points for longitudinal waves decrease within a limited frequency range, while they increase within a larger frequency scope for transverse waves. Enhancing the rigidity of the imperfect interfaces also enables shifting of the topological phase transition point within a broader frequency range for longitudinal waves and a confined range for transverse waves. The transition of topologically protected interface modes in the transmission performance of a twenty-cell system is verified, which include altering frequencies, switching from interface mode to edge mode. Overall, this study provides a new approach and guideline for controlling topological phase transition in composite and soft phononic crystal systems.Comment: 39 pages,8 figure

Vertebrate Paralogous MEF2 Genes: Origin, Conservation, and Evolution

BACKGROUND: The myocyte enhancer factor 2 (MEF2) gene family is broadly expressed during the development and maintenance of muscle cells. Although a great deal has been elucidated concerning MEF2 transcription factors' regulation of specific gene expression in diverse programs and adaptive responses, little is known about the origin and evolution of the four members of the MEF2 gene family in vertebrates. METHODOLOGY/PRINCIPAL FINDINGS: By phylogenetic analyses, we investigated the origin, conservation, and evolution of the four MEF2 genes. First, among the four MEF2 paralogous branches, MEF2B is clearly distant from the other three branches in vertebrates, mainly because it lacks the HJURP_C (Holliday junction recognition protein C-terminal) region. Second, three duplication events might have occurred to produce the four MEF2 paralogous genes and the latest duplication event occurred near the origin of vertebrates producing MEF2A and MEF2C. Third, the ratio (K(a)/K(s)) of non-synonymous to synonymous nucleotide substitution rates showed that MEF2B evolves faster than the other three MEF2 proteins despite purifying selection on all of the four MEF2 branches. Moreover, a pair model of M0 versus M3 showed that variable selection exists among MEF2 proteins, and branch-site analysis presented that sites 53 and 64 along the MEF2B branch are under positive selection. Finally, and interestingly, substitution rates showed that type II MADS genes (i.e., MEF2-like genes) evolve as slowly as type I MADS genes (i.e., SRF-like genes) in animals, which is inconsistent with the fact that type II MADS genes evolve much slower than type I MADS genes in plants. CONCLUSION: Our findings shed light on the relationship of MEF2A, B, C, and D with functional conservation and evolution in vertebrates. This study provides a rationale for future experimental design to investigate distinct but overlapping regulatory roles of the four MEF2 genes in various tissues