On the Coupling Time of the Heat-Bath Process for the Fortuin–Kasteleyn Random–Cluster Model

We consider the coupling from the past implementation of the random-cluster heat-bath process, and study its random running time, or coupling time. We focus on hypercubic lattices embedded on tori, in dimensions one to three, with cluster fugacity at least one. We make a number of conjectures regarding the asymptotic behaviour of the coupling time, motivated by rigorous results in one dimension and Monte Carlo simulations in dimensions two and three. Amongst our findings, we observe that, for generic parameter values, the distribution of the appropriately standardized coupling time converges to a Gumbel distribution, and that the standard deviation of the coupling time is asymptotic to an explicit universal constant multiple of the relaxation time. Perhaps surprisingly, we observe these results to hold both off criticality, where the coupling time closely mimics the coupon collector's problem, and also at the critical point, provided the cluster fugacity is below the value at which the transition becomes discontinuous. Finally, we consider analogous questions for the single-spin Ising heat-bath process

Isolation-by-Distance and Outbreeding Depression Are Sufficient to Drive Parapatric Speciation in the Absence of Environmental Influences

A commonly held view in evolutionary biology is that speciation (the emergence of genetically distinct and reproductively incompatible subpopulations) is driven by external environmental constraints, such as localized barriers to dispersal or habitat-based variation in selection pressures. We have developed a spatially explicit model of a biological population to study the emergence of spatial and temporal patterns of genetic diversity in the absence of predetermined subpopulation boundaries. We propose a 2-D cellular automata model showing that an initially homogeneous population might spontaneously subdivide into reproductively incompatible species through sheer isolation-by-distance when the viability of offspring decreases as the genomes of parental gametes become increasingly different. This simple implementation of the Dobzhansky-Muller model provides the basis for assessing the process and completion of speciation, which is deemed to occur when there is complete postzygotic isolation between two subpopulations. The model shows an inherent tendency toward spatial self-organization, as has been the case with other spatially explicit models of evolution. A well-mixed version of the model exhibits a relatively stable and unimodal distribution of genetic differences as has been shown with previous models. A much more interesting pattern of temporal waves, however, emerges when the dispersal of individuals is limited to short distances. Each wave represents a subset of comparisons between members of emergent subpopulations diverging from one another, and a subset of these divergences proceeds to the point of speciation. The long-term persistence of diverging subpopulations is the essence of speciation in biological populations, so the rhythmic diversity waves that we have observed suggest an inherent disposition for a population experiencing isolation-by-distance to generate new species

Impact of IL-28B polymorphisms on pegylated interferon plus ribavirin treatment response in children and adolescents infected with HCV genotypes 1 and 4

IL-28B polymorphisms are predictors of response to therapy in adults infected with hepatitis C. We do not know whether they are markers of response to therapy in children and adolescents. The aim of this study was to determine whether single-nucleotide polymorphisms (SNPs) in the IL-28B gene could influence the probability of response to therapy compared with other known baseline prognostic factors and correlate with clinical findings in pediatric patients infected with hepatitis C virus (HCV) genotypes 1 or 4. We determined three SNPs of IL-28B (rs12979860, rs12980275, and rs8099917) in 82 patients with chronic HCV infection treated with pegylated interferon alpha and ribavirin (peg-IFNα/RBV). Treatment response and clinical data were analyzed. Overall, sustained virological response (SVR) was achieved by 45 % of patients infected with difficult-to-treat HCV genotypes 1 and 4. Except for IL-28B polymorphisms, there was no association of SVR with any other clinical data. IL-28B rs12979860 CC [odds ratio (OR), 6.81; p = 0.001] and rs8099917 TT (OR, 3.14; p = 0.013) genotypes were associated with higher SVR rates. IL-28B rs12980275 was not significantly associated with SVR ( p = 0.058). Only the distribution between CC and CT-TT genotypes of rs12979860 significantly differentiated patients achieving early virological response (EVR) (OR, 10.0; p = 0.011). Children with the rs12979860 CC genotype had significantly higher baseline viral load compared with CT-TT patients ( p = 0.010). In children and adolescents chronically infected with HCV genotypes 1 and 4, IL-28B rs12979860 and rs8099917 polymorphisms were the only predictors of response to peg-IFN/RBV

Diversification and Specialization of Plant RBR Ubiquitin Ligases

Background: RBR ubiquitin ligases are components of the ubiquitin-proteasome system present in all eukaryotes. They are characterized by having the RBR (RING – IBR – RING) supradomain. In this study, the patterns of emergence of RBR genes in plants are described. Methodology/Principal Findings: Phylogenetic and structural data confirm that just four RBR subfamilies (Ariadne, ARA54, Plant I/Helicase and Plant II) exist in viridiplantae. All of them originated before the split that separated green algae from the rest of plants. Multiple genes of two of these subfamilies (Ariadne and Plant II) appeared in early plant evolution. It is deduced that the common ancestor of all plants contained at least five RBR genes and the available data suggest that this number has been increasing slowly along streptophyta evolution, although losses, especially of Helicase RBR genes, have also occurred in several lineages. Some higher plants (e. g. Arabidopsis thaliana, Oryza sativa) contain a very large number of RBR genes and many of them were recently generated by tandem duplications. Microarray data indicate that most of these new genes have low-level and sometimes specific expression patterns. On the contrary, and as occurs in animals, a small set of older genes are broadly expressed at higher levels. Conclusions/Significance: The available data suggests that the dynamics of appearance and conservation of RBR genes is quite different in plants from what has been described in animals. In animals, an abrupt emergence of many structurall

14-3-3ε Is Required for Germ Cell Migration in Drosophila

Although 14-3-3 proteins participate in multiple biological processes, isoform-specific specialized functions, as well as functional redundancy are emerging with tissue and developmental stage-specificity. Accordingly, the two 14-3-3ε proteins in Drosophila exhibit functional specificity and redundancy. Homozygotes for loss of function alleles of D14-3-3ε contain significantly fewer germ line cells (pole cells) in their gonads, a phenotype not shared by mutants in the other 14-3-3 gene leo. We show that although D14-3-3ε is enriched within pole cells it is required in mesodermal somatic gonad precursor cells which guide pole cells in their migration through the mesoderm and coalesce with them to form the embryonic gonad. Loss of D14-3-3ε results in defective pole cell migration, reduced pole cell number. We present evidence that D14-3-3ε loss results in reduction or loss of the transcription factor Zfh-1, one of the main regulatory molecules of the pole cell migration, from the somatic gonad precursor cells

Phylogenetic Constraints Do Not Explain the Rarity of Nitrogen-Fixing Trees in Late-Successional Temperate Forests

Symbiotic nitrogen (N)-fixing trees are rare in late-successional temperate forests, even though these forests are often N limited. Two hypotheses could explain this paradox. The 'phylogenetic constraints hypothesis' states that no late-successional tree taxa in temperate forests belong to clades that are predisposed to N fixation. Conversely, the 'selective constraints hypothesis' states that such taxa are present, but N-fixing symbioses would lower their fitness. Here we test the phylogenetic constraints hypothesis.Using U.S. forest inventory data, we derived successional indices related to shade tolerance and stand age for N-fixing trees, non-fixing trees in the 'potentially N-fixing clade' (smallest angiosperm clade that includes all N fixers), and non-fixing trees outside this clade. We then used phylogenetically independent contrasts (PICs) to test for associations between these successional indices and N fixation. Four results stand out from our analysis of U.S. trees. First, N fixers are less shade-tolerant than non-fixers both inside and outside of the potentially N-fixing clade. Second, N fixers tend to occur in younger stands in a given geographical region than non-fixers both inside and outside of the potentially N-fixing clade. Third, the potentially N-fixing clade contains numerous late-successional non-fixers. Fourth, although the N fixation trait is evolutionarily conserved, the successional traits are relatively labile.These results suggest that selective constraints, not phylogenetic constraints, explain the rarity of late-successional N-fixing trees in temperate forests. Because N-fixing trees could overcome N limitation to net primary production if they were abundant, this study helps to understand the maintenance of N limitation in temperate forests, and therefore the capacity of this biome to sequester carbon

Impact of Selection and Demography on the Diffusion of Lactase Persistence

BACKGROUND: The lactase enzyme allows lactose digestion in fresh milk. Its activity strongly decreases after the weaning phase in most humans, but persists at a high frequency in Europe and some nomadic populations. Two hypotheses are usually proposed to explain the particular distribution of the lactase persistence phenotype. The gene-culture coevolution hypothesis supposes a nutritional advantage of lactose digestion in pastoral populations. The calcium assimilation hypothesis suggests that carriers of the lactase persistence allele(s) (LCT*P) are favoured in high-latitude regions, where sunshine is insufficient to allow accurate vitamin-D synthesis. In this work, we test the validity of these two hypotheses on a large worldwide dataset of lactase persistence frequencies by using several complementary approaches. METHODOLOGY: We first analyse the distribution of lactase persistence in various continents in relation to geographic variation, pastoralism levels, and the genetic patterns observed for other independent polymorphisms. Then we use computer simulations and a large database of archaeological dates for the introduction of domestication to explore the evolution of these frequencies in Europe according to different demographic scenarios and selection intensities. CONCLUSIONS: Our results show that gene-culture coevolution is a likely hypothesis in Africa as high LCT*P frequencies are preferentially found in pastoral populations. In Europe, we show that population history played an important role in the diffusion of lactase persistence over the continent. Moreover, selection pressure on lactase persistence has been very high in the North-western part of the continent, by contrast to the South-eastern part where genetic drift alone can explain the observed frequencies. This selection pressure increasing with latitude is highly compatible with the calcium assimilation hypothesis while the gene-culture coevolution hypothesis cannot be ruled out if a positively selected lactase gene was carried at the front of the expansion wave during the Neolithic transition in Europe

Statistical significance of cis-regulatory modules

BACKGROUND: It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. RESULTS: We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. CONCLUSION: The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM) and MODSTORM software

The Spread of Inequality

The causes of socioeconomic inequality have been debated since the time of Plato. Many reasons for the development of stratification have been proposed, from the need for hierarchical control over large-scale irrigation systems to the accumulation of small differences in wealth over time via inheritance processes. However, none of these explains how unequal societies came to completely displace egalitarian cultural norms over time. Our study models demographic consequences associated with the unequal distribution of resources in stratified societies. Agent-based simulation results show that in constant environments, unequal access to resources can be demographically destabilizing, resulting in the outward migration and spread of such societies even when population size is relatively small. In variable environments, stratified societies spread more and are also better able to survive resource shortages by sequestering mortality in the lower classes. The predictions of our simulation are provided modest support by a range of existing empirical studies. In short, the fact that stratified societies today vastly outnumber egalitarian societies may not be due to the transformation of egalitarian norms and structures, but may instead reflect the more rapid migration of stratified societies and consequent conquest or displacement of egalitarian societies over time