Search

We consider a branching population with arbitrary lifetime distribution and Poissonian births. Moreover, individuals experience mutations at Poissonian rate. This mechanism leads to a partition of the population by type: the allelic partition. We focus on the frequency spectrum A (k , t) which counts the number of families of size k at time t. Our main goal is to study the asymptotic error made in some approximations of the frequency spectrum. [ABSTRACT FROM AUTHOR]

The forces driving regression of biologically functionless traits remain disputed. There is ongoing debate regarding whether selection, as opposed to disuse and neutral mutations, is involved in this process. Cave species are of particular relevance for study in this regard because in continuous darkness all traits that depend on information from light, such as eyes, dark pigmentation and certain behaviours, abruptly lose their function. Recently, strong selection driving reduction has again been proposed, which relied on modelling analyses based on assumptions such as immigration of surface alleles into the cave forms or no fitness difference existing between Astyanax surface and cave fish. The validity of these assumptions, often applied to reject neutral processes in functionless traits, is questioned in this review. Morphological variation in a trait resulting from genetic variability is typical of biologically functionless traits and is particularly notable in phylogenetically young cave species. It is the most evident indicator of loss of selection, which normally enforces uniformity to guarantee optimal functionality. Phenotypic and genotypic variability in Astyanax cave fish eyes does not derive from genetic introgression by the surface form, but from regressive mutations not being eliminated by selection. This matches well with the principles of Kimura's neutral theory of molecular evolution. [ABSTRACT FROM AUTHOR]

Highlights • A mathematical model that explicitly considers nucleotides, codons, amino acids, and the degeneracy of the standard genetic code is elaborated. • The model is based on the neutral theory of molecular evolution. • A control for neutral evolution is derived and used as a neutrality test, which allows to measure selective pressures such as positive, negative, and neutral selection. • Our model and the neutrality test constitute a baseline to compare the evolution of any protein. Abstract A neutral evolution model that explicitly considers codons, amino acids, and the degeneracy of the genetic code is developed. The model is built from nucleotides up to amino acids, and it represents a refinement of the neutral theory of molecular evolution. The model is based on a stochastic process that leads to a stationary probability distribution of amino acids. The latter is used as a neutral test of evolution. We provide some examples for assessing the neutrality test for a small set of protein sequences. The Jukes-Cantor model is generalized to deal with amino acids and it is compared with our neutral model, along with the empirical BLOSUM62 substitution model. The neutral test provides a baseline to which the evolution of any protein can be analyzed, and it clearly helps in discerning putative amino acids with unexpected frequencies that might be under positive or negative selection. Our model and neutral test are as universal as the standard genetic code. [ABSTRACT FROM AUTHOR]

Background: The neutral theory of Motoo Kimura stipulates that evolution is mostly driven by neutral mutations. However adaptive pressure eventually leads to changes in phenotype that involve non-neutral mutations. The relation between neutrality and adaptation has been studied in the context of RNA before and here we further study transitional mutations in the context of degenerate (plastic) RNA sequences and genetic assimilation. We propose quasineutral mutations, i.e. mutations which preserve an element of the phenotype set, as minimal mutations and study their properties. We also propose a general probabilistic interpretation of genetic assimilation and specialize it to the Boltzmann ensemble of RNA sequences. Results: We show that degenerate sequences i.e. sequences with more than one structure at the MFE level have the highest evolvability among all sequences and are central to evolutionary innovation. Degenerate sequences also tend to cluster together in the sequence space. The selective pressure in an evolutionary simulation causes the population to move towards regions with more degenerate sequences, i.e. regions at the intersection of different neutral networks, and this causes the number of such sequences to increase well beyond the average percentage of degenerate sequences in the sequence space. We also observe that evolution by quasineutral mutations tends to conserve the number of base pairs in structures and thereby maintains structural integrity even in the presence of pressure to the contrary. Conclusions: We conclude that degenerate RNA sequences play a major role in evolutionary adaptation. [ABSTRACT FROM AUTHOR]

Abstract Objectives Readily apparent cyclin E1 expression occurs in 50% of HGSOC, but only half are linked to 19q12 locus amplification. The amplified/cyclin E1hi subset has intact BRCA1/2 , unfavorable outcome, and is potentially therapeutically targetable. We studied whether non-amplified/cyclin E1hi HGSOC has similar characteristics. We also assessed the expression of cyclin E1 degradation-associated proteins, FBXW7 and USP28, as potential drivers of high cyclin E1 expression in both subsets. Methods 262 HGSOC cases were analyzed by in situ hybridization for 19q12 locus amplification and immunohistochemistry for cyclin E1, URI1 (another protein encoded by the 19q12 locus), FBXW7 and USP28 expression. Tumors were classified by 19q12 amplification status and correlated to cyclin E1 and URI1 expression, BRCA1/2 germline mutation, FBXW7 and USP28 expression, and clinical outcomes. Additionally, we assessed the relative genomic instability of amplified/cyclin E1hi and non-amplified/cyclin E1hi groups of HGSOC datasets from The Cancer Genome Atlas. Results Of the 82 cyclin E1hi cases, 43 (52%) were amplified and 39 (48%) were non-amplified. Unlike amplified tumors, non-amplified/cyclin E1hi tumor status was not mutually exclusive with gBRCA1/2 mutation. The non-amplified/cyclin E1hi group had significantly increased USP28, while the amplified/cyclin E1hi cancers had significantly lower FBXW7 expression consistent with a role for both in stabilizing cyclin E1. Notably, only the amplified/cyclin E1hi subset was associated with genomic instability and had a worse outcome than non-amplified/cyclin E1hi group. Conclusions Amplified/cyclin E1hi and non-amplified/cyclin E1hi tumors have different pathological and biological characteristics and clinical outcomes indicating that they are separate subsets of cyclin E1hi HGSOC. Graphical abstract Unlabelled Image Highlights • Cyclin E1hi/non-amplified HGSOC can be either BRCA1/2 wildtype or mutated. • Cyclin E1hi/non-amplified HGSOC have better outcomes than Cyclin E1hi/amplified cases. • High USP28 expression is a likely driver of high cyclin E1 in non-amplified HGSOC. • Low FBXW7 expression is likely to augment high cyclin E1 in amplified HGSOC. • Chromosomal instability is significantly higher in cyclin E1hi/amplified cases. [ABSTRACT FROM AUTHOR]

Highlights • The codon bias of BAV is affected by the pressure of selection and mutation. • The codon bias of 12 genes is related to their function or their host. • The codon bias of the most affected gene by mutation pressure is VP12 gene related to RNA binding protein. • The codon bias of VP9 gene related outer coat protein is the highest in all coding gene of different BAV strains. Abstract By using DNA Star, CUSP of EMBOSS, Codon W and IBM SPSS Statistics, nucleotide composition and codon usage pattern of 115 genes are researched in 37 BAVs. It shows that the composition of all genes prefers to AU, compared to CG, and for most of genes, the order is A, U, G and C in the virus. The ENC-values of the genes are slightly high which shows the weak codon bias, in which the codon bias of VP9 gene is the highest. The codon usage pattern of 12 different genes is different and related to their composition, their function or their host. For example, VP9 gene encoding viral spike protein in contact with different hosts spread dispersedly and VP1, VP2, VP3 and VP4 genes encoding the capsid protein are concentrated on first quadrant in correspondence analysis. The ENC of VP5 is correlated to GC 3s in correlation analysis. The points of VP12 gene are tightly close to the expected curve in the ENC-plot analysis but GC 12 is not related to GC 3 in neutrality analysis. All analysis indicates the codon usage pattern of 12 genes is influenced by both natural selection and neutral mutation in a different extent in BAV. As a pathogen of viral encephalitis, compositional analysis and codon bias analysis of BAV can provide a theoretical basis for the disease control. [ABSTRACT FROM AUTHOR]

Theory and empirical patterns suggest a disproportionate role for sex chromosomes in evolution and speciation. Focusing on ZW sex determination (females ZW, males ZZ; the system in birds, many snakes, and lepidopterans), I review how evolutionary dynamics are expected to differ between the Z, W and the autosomes, discuss how these differences may lead to a greater role of the sex chromosomes in speciation and use data from birds to compare relative evolutionary rates of sex chromosomes and autosomes. Neutral mutations, partially or completely recessive beneficial mutations, and deleterious mutations under many conditions are expected to accumulate faster on the Z than on autosomes. Sexually antagonistic polymorphisms are expected to arise on the Z, raising the possibility of the spread of preference alleles. The faster accumulation of many types of mutations and the potential for complex evolutionary dynamics of sexually antagonistic traits and preferences contribute to a role for the Z chromosome in speciation. A quantitative comparison among a wide variety of bird species shows that the Z tends to have less within‐population diversity and greater between‐species differentiation than the autosomes, likely due to both adaptive evolution and a greater rate of fixation of deleterious alleles. The W chromosome also shows strong potential to be involved in speciation, in part because of its co‐inheritance with the mitochondrial genome. While theory and empirical evidence suggest a disproportionate role for sex chromosomes in speciation, the importance of sex chromosomes is moderated by their small size compared to the whole genome. [ABSTRACT FROM AUTHOR]

A major challenge in cancer genomics is identifying "driver" mutations from the many neutral "passenger" mutations within a given tumor. To identify driver mutations that would otherwise be lost within mutational noise, we filtered genomic data by motifs that are critical for kinase activity. In the first step of our screen, we used data from the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas to identify kinases with truncation mutations occurring within or before the kinase domain. The top 30 tumor-suppressing kinases were aligned, and hotspots for loss-of-function (LOF) mutations were identified on the basis of amino acid conservation and mutational frequency. The functional consequences of new LOF mutations were biochemically validated, and the top 15 hotspot LOF residues were used in a pan-cancer analysis to define the tumor-suppressing kinome. A ranked list revealed MAP2K7, an essential mediator of the c-Jun N-terminal kinase (JNK) pathway, as a candidate tumor suppressor in gastric cancer, despite its mutational frequency falling within the mutational noise for this cancer type. The majority of mutations in MAP2K7 abolished its catalytic activity, and reactivation of the JNK pathway in gastric cancer cells harboring LOF mutations in MAP2K7 or the downstream kinase JNK suppressed clonogenicity and growth in soft agar, demonstrating the functional relevance of inactivating the JNK pathway in gastric cancer. Together, our data highlight a broadly applicable strategy to identify functional cancer driver mutations and define the JNK pathway as tumor-suppressive in gastric cancer. [ABSTRACT FROM AUTHOR]

A population genetics model based on a multitype branching process, or equivalently a Galton–Watson branching process for multiple alleles, is presented. The diffusion limit forward Kolmogorov equation is derived for the case of neutral mutations. The asymptotic stationary solution is obtained and has the property that the extant population partitions into subpopulations whose relative sizes are determined by mutation rates. An approximate time-dependent solution is obtained in the limit of low mutation rates. This solution has the property that the system undergoes a rapid transition from a drift-dominated phase to a mutation-dominated phase in which the distribution collapses onto the asymptotic stationary distribution. The changeover point of the transition is determined by the per-generation growth factor and mutation rate. The approximate solution is confirmed using numerical simulations. [ABSTRACT FROM AUTHOR]

Background We have previously defined mechanisms of intimal hyperplasia that could be targets for molecular therapeutics aimed at vascular pathology. However, biocompatible nanocarriers are needed for effective delivery. Cationic liposomes (CLPs) have been demonstrated as effective nanocarriers in vitro . However, in vivo success has been hampered by cytotoxicity. Recently, neutral PEGylated liposomes (PLPs) have been modified with cell-penetrating peptides (CPPs) to enhance cellular uptake. We aim to establish CPP-modified neutral liposomes as viable molecular nanocarriers in vascular smooth muscle cells. Methods CLPs, PLPs, and CPP-modified PLPs (R8-PLPs) were assembled with short interfering RNA (siRNA) via ethanol injection. Characterization studies determined liposomal morphology, size, and charge. siRNA encapsulation efficiency was measured via RiboGreen assay. Vascular smooth muscle cells were exposed to equal lipid/siRNA across all groups. Rhodamine-labeled liposomes were used to quantify cell association via fluorometry, live/dead dual stain was used to measure cytotoxicity, and gene silencing was measured by quantitative polymerase chain reaction. Results R8-PLPs exhibited increased encapsulation efficiency equivalent to CLPs. PLPs and R8-PLP-5 mol% and R8-PLP-10 mol% had no cytotoxic effect. CLPs demonstrated significant cytotoxicity. R8-PLP-5 mol% and R8-PLP-10 mol% exhibited increased cell association versus PLPs. R8-PLP-10 mol% resulted in significant gene silencing, in a manner dependent on lipid-to-siRNA load capacity. Conclusions The negligible cytotoxicity and enhanced cellular association and gene silencing capacity exhibited by R8-PLPs reveal this class of liposomes as a candidate for future applications. Further modifications for optimizing R8-PLPs are still warranted to improve efficacy, and in vivo studies are needed for translational development. However, this could prove to be an optimal nanocarrier for vascular gene therapeutics. [ABSTRACT FROM AUTHOR]

Evolutionary game theory is a mathematical approach to studying how social behaviors evolve. In many recent works, evolutionary competition between strategies is modeled as a stochastic process in a finite population. In this context, two limits are both mathematically convenient and biologically relevant: weak selection and large population size. These limits can be combined in different ways, leading to potentially different results. We consider two orderings: the $$wN$$ limit, in which weak selection is applied before the large population limit, and the $$Nw$$ limit, in which the order is reversed. Formal mathematical definitions of the $$Nw$$ and $$wN$$ limits are provided. Applying these definitions to the Moran process of evolutionary game theory, we obtain asymptotic expressions for fixation probability and conditions for success in these limits. We find that the asymptotic expressions for fixation probability, and the conditions for a strategy to be favored over a neutral mutation, are different in the $$Nw$$ and $$wN$$ limits. However, the ordering of limits does not affect the conditions for one strategy to be favored over another. [ABSTRACT FROM AUTHOR]

Nectopsyche genus is common in standing or slowly flowing aquatic ecosystems in the New World. Their taxonomy was unduly based too long on forewing pattern that is easily lost in alcohol. In this created taxonomic chaos management projects are unable to determine these beautiful and common animals. We have elaborated a new taxonomy with easy procedure to delineate closely related incipient sibling species without forewing pattern. Our taxonomy enables us to determine specimens collected and stored in alcohol. We have applied the fine phenomics of adaptive speciation traits of the sigmoid profile of the phallicata and of the apicomesal lobe on gonopods. They were combined, if necessary, with nonadaptive neutral traits of the periphallic organs. These adaptive speciation traits are subtle and stable, they are more super than magic. We briefly review: (1) Are speciation traits really subtle? (2) Are speciation traits super or magic? (3) Why neutral traits are variable? (4) Why adaptive traits are stable? We survey the possible adaptive and neutral traits in the Nectopsyche genus. Our adaptive-neutral distinction has potential in character ranking to establish recent pass, contemporary and old historical divergences in coalescence. Applying the adaptive - neutral distinction, as well as the generality, locality and parsimony principles we have elaborated a character ranking sytem for the genus, for the species groups and for the species with a revised lineage structure in the Nectopsyche genus. Six species grous have been characterised and fourty four new species have been described and grouped in the four species groups. (1) N. candida species group: bonta, buzoga, dombora, flinti, garenoa, lenula, obla. (2) N. pavida species group: alma, bobita, capota, hasonla, kifela, kinilta, kurta, laposka, nemritka, nyaka, oliveri, poca, ritka, salka, silva, sima, terda, vagota, valla. (3) N. punctata species group: eka, kurtula, letra, padka, vezna. (4) N. gemma species group: bunka, eltera, flintorum, huzva, iva, kajla, nilta, pohoka, setfela, suta, taga, tarka, tomora. The species of N. argentata, N. cubana, N. gemmoides, N. jenseni, N. punctata and several unexamined taxa probably represent species complexes. An expected comprehensive revision of the entire genus is needed including forewing pattern with fine phenomics. Inevitable are the re-examination of the speciation traits of the old types and to scrutinise the species status of so called widely distributed species applying the fine phenomics of speciation traits. [ABSTRACT FROM AUTHOR]

Caged neurotransmitters, in combination with focused light beams, enable precise interrogation of neuronal function, even at the level of single synapses. However, most caged transmitters are, surprisingly, severe antagonists of ionotropic gamma-aminobutyric acid (GABA) receptors. By conjugation of a large, neutral dendrimer to a caged GABA probe we introduce a 'cloaking' technology that effectively reduces such antagonism to very low levels. Such cloaked caged compounds will enable the study of the signaling of the inhibitory neurotransmitter GABA in its natural state using two-photon uncaging microscopy for the first time. [ABSTRACT FROM AUTHOR]

Coagulation factor Leiden mutation has been described as a common genetic risk factor for venous thrombosis; however, this mutation was reported to be practically absent in an African population. Recently, a novel non-sense mutation in the gene encoding factor V has been associated with the risk of occurrence of cardio-cerebrovascular diseases such as stroke and venous thrombosis. The aim of the present study was to investigate whether the factor V Leiden (FVL) and C2491T non-sense mutations are associated with the risk of developing myocardial infarction. Genotyping of FVL and C2491T FV was performed using the polymerase chain reaction restriction fragment length polymorphism method on a sample of 100 patients with myocardial infarction as well as 211 controls. In the study population, the frequency of the FVL mutation was practically zero. However, with regard to the C2491T mutation, the TT genotype was associated with an increased risk of myocardial infarction [odds ratio (OR)=3.16, 95% confidence interval (CI): 1.29-7.71, P=0.03]. A significant association between the C2491T FV mutation and the risk of myocardial infarction was identified using recessive (OR=2.74, 95% CI: 1.14-6.58, P=0.04), dominant (OR=1.85, 95% CI: 1.13-3.04, P=0.02) and additive (OR=1.88, 95% CI: 1.25-2.80, P=0.004) models. Furthermore, a positive correlation was found between the presence of the C2491T FV mutation and hypertension (P=0.02), which is associated with myocardial infarction. In conclusion, the results of the present study suggested that the C2491T non-sense mutation of the FV gene may be a risk factor for myocardial infarction in a Moroccan population. [ABSTRACT FROM AUTHOR]

In finite populations the action of neutral mutations is balanced by genetic drift, leading to a stationary distribution of alleles that displays a transition between two different behaviors. For small mutation rates most individuals will carry the same allele at equilibrium, whereas for high mutation rates of the alleles will be randomly distributed with frequencies close to one half for a biallelic gene. For well-mixed haploid populations the mutation threshold is μ c = 1 / 2 N , where N is the population size. In this paper we study how spatial structure affects this mutation threshold. Specifically, we study the stationary allele distribution for populations placed on regular networks where connected nodes represent potential mating partners. We show that the mutation threshold is sensitive to spatial structure only if the number of potential mates is very small. In this limit, the mutation threshold decreases substantially, increasing the diversity of the population at considerably low mutation rates. Defining k c as the degree of the network for which the mutation threshold drops to half of its value in well-mixed populations we show that k c grows slowly as a function of the population size, following a power law. Our calculations and simulations are based on the Moran model and on a mapping between the Moran model with mutations and the voter model with opinion makers. [ABSTRACT FROM AUTHOR]

Simulation of orbital phenomena is often difficult because of the non-continuum nature of the flow, which forces the use of particle methods, and the disparate time scales, which make long run times necessary. In this work, the computational work load has been reduced by taking advantage of the low number of collisions between different species. This allows each population of particles to be brought into convergence separately using a time step size optimized for its particular motion. The converged populations are then brought together to simulate low probability phenomena, such as ionization or excitation, on much longer time scales. The result of this technique has the effect of reducing run times by a factor of 10 3 – 10 4 . The technique was applied to the simulation of a low earth orbit neutral species sensor with an ionizing element. Comparison with laboratory experiments of ion impacts generated by electron flux shows very good agreement. [ABSTRACT FROM AUTHOR]

Summary The most commonly used locomotor strategy in rodents is left-right limb alternation. Mutation of the axon guidance molecule EphA4 profoundly alters this basic locomotor pattern to synchrony. Here we report that conditional mutation of EphA4 in spinal interneurons expressing the transcription factor Lbx1 degrades the robustness in the expression of left-right alternating gait during development. Lbx1 EphA4 conditional mice exhibit alternating gait when walking on ground, but synchronous gait in environments with decreased weight-load, like swimming and airstepping. Using cell-type-specific, transient pharmacogenetic silencing approaches, we attribute this behavioral gait switch to neuronal activity of dorsal Lbx1 spinal interneurons. We also found that in Lbx1 EphA4 conditional mice these dorsal interneurons form aberrant bilateral connections to motor neurons, thereby indirectly transmitting received unilateral proprioceptive sensory information to both spinal sides. Together, our findings reveal the behavioral and circuit-level impact of conditional EphA4 mutation in a transcriptionally defined spinal interneuron subpopulation. [ABSTRACT FROM AUTHOR]

Background: Bloom-forming cyanobacteria cause toxic algae outbreaks in lakes and reservoirs. We aimed to explore and quantify mutation events occurring within the large mcy gene cluster (55 kbp) encoding microcystin (MC) biosynthesis that inactivate MC net production. For this purpose we developed a workflow to detect mutations in situ occurring anywhere within the large mcy gene cluster as amplified from one single filament of the red-pigmented cyanobacterium Planktothrix rubescens. From five lakes of the Alps eight hundred Planktothrix filaments were isolated and each individual filament was analyzed for mutations affecting the mcy genes. Results: Mutations inactivating MC synthesis were either through an insertion element ISPlr1 or the partial deletion of mcy genes. Neutral mutations not affecting MC biosynthesis occurred within two intergenic spacer regions, either through the insertion of a Holliday-junction resolvase RusA or ISPlr1. Altogether, the insertions affected a few mcy genes only and their location was correlated with regions similar to repetitive extragenic palindromic DNA sequences (REPs). Taking all of the filaments together, the mutations leading to the inactivation of MC synthesis were more rare (0.5–6.9 %), when compared with the neutral mutations (7.5–20.6 %). On a spatial-temporal scale the ratio of MC synthesis-inactivating vs. neutral mutations was variable, e.g., the filament abundance carrying partial deletion of mcyD (5.2–19.4 %) and/or mcyHA (0–7.3 %) exceeded the abundance of neutral mutations. Conclusions: It is concluded that insertion events occurring within the Planktothrix mcy gene cluster are predictable due to their correlation with REPs. The frequency of occurrence of the REPs within the mcy gene cluster of Planktothrix relates to the rather common mutation of mcy genes in Planktothrix. Spatial-temporal variable conditions may favor the emergence of partial mcy deletion mutants in Planktothrix, in particular a higher proportion of genotypes resulting in inactivation of MC synthesis might be caused by increased ISPlr1 activity. [ABSTRACT FROM AUTHOR]

Angiosperm mitochondrial genes appear to have very low mutation rates, while non-gene regions expand, diverge, and rearrange quickly. One possible explanation for this disparity is that synonymous substitutions in plant mitochondrial genes are not truly neutral and selection keeps their occurrence low. If this were true, the explanation for the disparity in mutation rates in genes and non-genes needs to consider selection as well as mechanisms of DNA repair. Rps14 is co-transcribed with cob and rpl5 in most plant mitochondrial genomes, but in some genomes, rps14 has been duplicated to the nucleus leaving a pseudogene in the mitochondria. This provides an opportunity to compare neutral substitution rates in pseudogenes with synonymous substitution rates in the orthologs. Genes and pseudogenes of rps14 have been aligned among different species and the mutation rates have been calculated. Neutral substitution rates in pseudogenes and synonymous substitution rates in genes are significantly different, providing evidence that synonymous substitutions in plant mitochondrial genes are not completely neutral. The non-neutrality is not sufficient to completely explain the exceptionally low mutation rates in land plant mitochondrial genomes, but selective forces appear to play a small role. [ABSTRACT FROM AUTHOR]

The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution. [ABSTRACT FROM AUTHOR]

In 1974, Takeo Maruyama deduced that neutral mutations should, on average, be older than deleterious or beneficial ones. This theory is based on the diffusion approximation for a branching process, which considers mutations independently of one another and not as multiple groups of interconnected mutations with strong linkage disequilibrium (haplotypes). However, mammalian genomes contain thousands of haplotypes, in which beneficial, neutral, and deleterious mutations are tightly linked to each other. This complex haplotype organization should not be ignored for estimation of allelic ages. We employed our GEMA computer simulation program for genome evolution to re-evaluate Maruyama's phenomenon in modeled populations that include haplotypes approximating real genomes. We determined that only under specific conditions (high recombination rates and abundance of neutral mutations), the deleterious and beneficial mutations are younger than neutral ones as predicted by Maruyama. Under other conditions, the ages of negative, neutral, and beneficial mutations were almost the same. [ABSTRACT FROM AUTHOR]

The new iron(II) complex [Fe( bpta)2(EtOH)2(NCS)2] ( bpta = 3,3'-(1,2,4-thiadiazole-3,5-diyl) dipyridine; EtOH = ethanol) has been prepared by refluxing Fe(NCS)3 or Fe(NCS)2 with thionicotinamide in an ethanol solution and characterized by elemental analysis, infrared spectroscopy, thermal decomposition and X-ray structural analysis. The characterized compound is a mixture of three regioisomers resulting from differential coordination by the 3- and 5-position 2-pyridyl groups. The bpta ligand was generated in situ by the oxidation dimerization of thionicotinamide. X-ray single-crystal diffraction revealed that the crystal structure is centrosymmetric and the complex crystallizes in the triclinic space group P-1. The iron(II) atom lies in the centre of symmetry and it is octahedrally coordinated by two nitrogen atoms from two thiocyanate anions and two oxygen atoms from ethanol molecules in the equatorial plane and two nitrogen atoms of pyridine rings from two bpta ligands in the axial positions. This complex represents the second example of metal complex with bpta. [ABSTRACT FROM AUTHOR]

Why are mitochondria almost always inherited from one parent during sexual reproduction? Current explanations for this evolutionary mystery include conflict avoidance between the nuclear and mitochondrial genomes, clearing of deleterious mutations, and optimization of mitochondrial-nuclear coadaptation. Mathematical models, however, fail to show that uniparental inheritance can replace biparental inheritance under any existing hypothesis. Recent empirical evidence indicates that mixing two different but normal mitochondrial haplotypes within a cell (heteroplasmy) can cause cell and organism dysfunction. Using a mathematical model, we test if selection against heteroplasmy can lead to the evolution of uniparental inheritance. When we assume selection against heteroplasmy and mutations are neither advantageous nor deleterious (neutral mutations), uniparental inheritance replaces biparental inheritance for all tested parameter values. When heteroplasmy involves mutations that are advantageous or deleterious (non-neutral mutations), uniparental inheritance can still replace biparental inheritance. We show that uniparental inheritance can evolve with or without pre-existing mating types. Finally, we show that selection against heteroplasmy can explain why some organisms deviate from strict uniparental inheritance. Thus, we suggest that selection against heteroplasmy explains the evolution of uniparental inheritance. [ABSTRACT FROM AUTHOR]

The new iron(II) complex [Fe( bpta)2(EtOH)2(NCS)2] ( bpta = 3,3'-(1,2,4-thiadiazole-3,5-diyl) dipyridine; EtOH = ethanol) has been prepared by refluxing Fe(NCS)3 or Fe(NCS)2 with thionicotinamide in an ethanol solution and characterized by elemental analysis, infrared spectroscopy, thermal decomposition and X-ray structural analysis. The characterized compound is a mixture of three regioisomers resulting from differential coordination by the 3- and 5-position 2-pyridyl groups. The bpta ligand was generated in situ by the oxidation dimerization of thionicotinamide. X-ray single-crystal diffraction revealed that the crystal structure is centrosymmetric and the complex crystallizes in the triclinic space group P-1. The iron(II) atom lies in the centre of symmetry and it is octahedrally coordinated by two nitrogen atoms from two thiocyanate anions and two oxygen atoms from ethanol molecules in the equatorial plane and two nitrogen atoms of pyridine rings from two bpta ligands in the axial positions. This complex represents the second example of metal complex with bpta. [ABSTRACT FROM AUTHOR]

For a one- or two-dimensional lattice of finite length consisting of populations, each of which has the same population size, the classical stepping-stone model has been used to approximate the patterns of variation at neutral loci in geographic regions. In the pioneering papers by Maruyama (1970a, 1970b, 1971) the changes of gene frequency at a locus subject to neutral mutation between two alleles, migration, and random genetic drift were modeled by a vector autoregression model. Maruyama was able to use the spectrum of the migration matrix, but to do this he had to introduce approximations in which there was either extra mutation in the terminal populations, or extra migration from the subterminal population into the terminal population. In this paper a similar vector autoregression model is used, but it proves possible to obtain the eigenvalues and eigenvectors of the migration matrix without those approximations. Approximate formulas for the variances and covariances of gene frequencies in different populations are obtained, and checked by numerical iteration of the exact covariances of the vector autoregression model. [ABSTRACT FROM AUTHOR]

Over time, a population acquires neutral genetic substitutions as a consequence of random drift. A famous result in population genetics asserts that the rate, K, at which these substitutions accumulate in the population coincides with the mutation rate, u, at which they arise in individuals: K = u. This identity enables genetic sequence data to be used as a “molecular clock” to estimate the timing of evolutionary events. While the molecular clock is known to be perturbed by selection, it is thought that K = u holds very generally for neutral evolution. Here we show that asymmetric spatial population structure can alter the molecular clock rate for neutral mutations, leading to either Ku. Our results apply to a general class of haploid, asexually reproducing, spatially structured populations. Deviations from K = u occur because mutations arise unequally at different sites and have different probabilities of fixation depending on where they arise. If birth rates are uniform across sites, then K ≤ u. In general, K can take any value between 0 and Nu. Our model can be applied to a variety of population structures. In one example, we investigate the accumulation of genetic mutations in the small intestine. In another application, we analyze over 900 Twitter networks to study the effect of network topology on the fixation of neutral innovations in social evolution. [ABSTRACT FROM AUTHOR]