TY - JOUR AB - Bayesian inference is becoming a common statistical approach to phylogenetic estimation because, among other reasons, it allows for rapid analysis of large data sets with complex evolutionary models. Conveniently, Bayesian phylogenetic methods use currently available stochastic models of sequence evolution. However, as with other model-based approaches, the results of Bayesian inference are conditional on the assumed model of evolution: inadequate models (models that poorly fit the data) may result in erroneous inferences. In this article, I present a Bayesian phylogenetic method that evaluates the adequacy of evolutionary models using posterior predictive distributions. By evaluating a model's posterior predictive performance, an adequate model can be selected for a Bayesian phylogenetic study. Although I present a single test statistic that assesses the overall (global) performance of a phylogenetic model, a variety of test statistics can be tailored to evaluate specific features (local performance) of evolutionary models to identify sources failure. The method presented here, unlike the likelihood-ratio test and parametric bootstrap, accounts for uncertainty in the phylogeny and model parameters. AU - Bollback, Jonathan P ID - 4349 IS - 7 JF - Molecular Biology and Evolution SN - 0737-4038 TI - Bayesian model adequacy and choice in phylogenetics VL - 19 ER - TY - JOUR AB - We introduce a general recursion for the probability of identity in state of two individuals sampled from a population subject to mutation, migration, and random drift in a two-dimensional continuum. The recursion allows for the interactions induced by density-dependent regulation of the population, which are inevitable in a continuous population. We give explicit series expansions for large neighbourhood size and for low mutation rates respectively and investigate the accuracy of the classical Malécot formula for these general models. When neighbourhood size is small, this formula does not give the identity even over large scales. However, for large neighbourhood size, it is an accurate approximation which summarises the local population structure in terms of three quantities: the effective dispersal rate, σe; the effective population density, ρe; and a local scale, κ, at which local interactions become significant. The results are illustrated by simulations. AU - Barton, Nicholas H AU - Depaulis, Frantz AU - Etheridge, Alison ID - 4263 IS - 1 JF - Theoretical Population Biology SN - 0040-5809 TI - Neutral evolution in spatially continuous populations VL - 61 ER - TY - JOUR AB - Until recently, it was impracticable to identify the genes that are responsible for variation in continuous traits, or to directly observe the effects of their different alleles. Now, the abundance of genetic markers has made it possible to identify quantitative trait loci (QTL) — the regions of a chromosome or, ideally, individual sequence variants that are responsible for trait variation. What kind of QTL do we expect to find and what can our observations of QTL tell us about how organisms evolve? The key to understanding the evolutionary significance of QTL is to understand the nature of inherited variation, not in the immediate mechanistic sense of how genes influence phenotype, but, rather, to know what evolutionary forces maintain genetic variability. AU - Barton, Nicholas H AU - Keightley, Peter ID - 4261 JF - Nature Reviews Genetics SN - 1471-0056 TI - Understanding quantitative genetic variation VL - 3 ER - TY - JOUR AB - Phylogenetic trees can be rooted by a number of criteria. Here, we introduce a Bayesian method for inferring the root of a phylogenetic tree by using one of several criteria: the outgroup, molecular clock, and nonreversible model of DNA substitution. We perform simulation analyses to examine the relative ability of these three criteria to correctly identify the root of the tree. The outgroup and molecular clock criteria were best able to identify the root of the tree, whereas the nonreversible model was able to identify the root only when the substitution process was highly nonreversible. We also examined the performance of the criteria for a tree of four species for which the topology and root position are well supported. Results of the analyses of these data are consistent with the simulation results. AU - Huelsenbeck, John AU - Bollback, Jonathan P AU - Levine, Amy ID - 4347 IS - 1 JF - Systematic Biology SN - 0039-7989 TI - Inferring the root of a phylogenetic tree VL - 51 ER - TY - JOUR AB - This paper presents a complete axiomatization of two decidable propositional real-time linear temporal logics: Event Clock Logic (EventClockTL) and Metric Interval Temporal Logic with past (MetricIntervalTL). The completeness proof consists of an effective proof building procedure for EventClockTL. From this result we obtain a complete axiomatization of MetricIntervalTL by providing axioms translating MetricIntervalTL formulae into EventClockTL formulae, the two logics being equally expressive. Our proof is structured to yield axiomatizations also for interesting fragments of these logics, such as the linear temporal logic of the real numbers (TLR). AU - Raskin, Jean AU - Schobbens, Pierre AU - Henzinger, Thomas A ID - 4407 IS - 1-2 JF - Theoretical Computer Science SN - 0304-3975 TI - Axioms for real-time logics VL - 274 ER - TY - JOUR AB - We studied the effect of multilocus balancing selection on neutral nucleotide variability at linked sites by simulating a model where diallelic polymorphisms are maintained at an arbitrary number of selected loci by means of symmetric overdominance. Different combinations of alleles define different genetic backgrounds that subdivide the population and strongly affect variability. Several multilocus fitness regimes with different degrees of epistasis and gametic disequilibrium are allowed. Analytical results based on a multilocus extension of the structured coalescent predict that the expected linked neutral diversity increases exponentially with the number of selected loci and can become extremely large. Our simulation results show that although variability increases with the number of genetic backgrounds that are maintained in the population, it is reduced by random fluctuations in the frequencies of those backgrounds and does not reach high levels even in very large populations. We also show that previous results on balancing selection in single-locus systems do not extend to the multilocus scenario in a straightforward way. Different patterns of linkage disequilibrium and of the frequency spectrum of neutral mutations are expected under different degrees of epistasis. Interestingly, the power to detect balancing selection using deviations from a neutral distribution of allele frequencies seems to be diminished under the fitness regime that leads to the largest increase of variability over the neutral case. This and other results are discussed in the light of data from the Mhc. AU - Navarro, Arcadio AU - Barton, Nicholas H ID - 4258 IS - 2 JF - Genetics SN - 0016-6731 TI - The effects of multilocus balancing selection on neutral variability VL - 161 ER - TY - JOUR AB - We extend current multilocus models to describe the effects of migration, recombination, selection, and nonrandom mating on sets of genes in diploids with varied modes of inheritance, allowing us to consider the patterns of nuclear and cytonuclear associations (disequilibria) under various models of migration. We show the relationship between the multilocus notation recently presented by Kirkpatrick, Johnson, and Barton (developed from previous work by Barton and Turelli) and the cytonuclear parameterization of Asmussen, Arnold, and Avise and extend this notation to describe associations between cytoplasmic elements and multiple nuclear genes. Under models with sexual symmetry, both nuclear-nuclear and cytonuclear disequilibria are equivalent. They differ, however, in cases involving some type of sexual asymmetry, which is then reflected in the asymmetric inheritance of cytoplasmic markers. An example given is the case of different migration rates in males and females; simulations using 2, 3, 4, or 5 unlinked autosomal markers with a maternally inherited cytoplasmic marker illustrate how nuclear-nuclear and cytonuclear associations can be used to separately estimate female and male migration rates. The general framework developed here allows us to investigate conditions where associations between loci with different modes of inheritance are not equivalent and to use this nonequivalence to test for deviations from simple models of admixture. AU - Orive, Maria AU - Barton, Nicholas H ID - 4259 IS - 3 JF - Genetics SN - 0016-6731 TI - Associations between cytoplasmic and nuclear loci in hybridizing populations VL - 162 ER - TY - JOUR AB - We have identified widerborst (wdb), a B' regulatory subunit of PP2A, as a conserved component of planar cell polarization mechanisms in both Drosophila and in zebrafish. In Drosophila, wdb acts at two steps during planar polarization of wing epithelial cells. It is required to organize tissue polarity proteins into proximal and distal cortical domains, thus determining wing hair orientation. It is also needed to generate the polarized membrane outgrowth that becomes the wing hair. Widerborst activates the catalytic subunit of PP2A and localizes to the distal side of a planar microtubule web that lies at the level of apical cell junctions. This suggests that polarized PP2A activation along the planar microtubule web is important for planar polarization. In zebrafish, two wdb homologs are required for convergent extension during gastrulation, supporting the conjecture that Drosophila planar cell polarization and vertebrate gastrulation movements are regulated by similar mechanisms. AU - Hannus, Michael AU - Feiguin, Fabian AU - Heisenberg, Carl-Philipp J AU - Eaton, Suzanne ID - 4209 IS - 14 JF - Development SN - 0950-1991 TI - Planar cell polarization requires Widerborst, a B′ regulatory subunit of protein phosphatase 2A VL - 129 ER - TY - JOUR AB - Vertebrate homologues of the Strabismus/van Gogh (stbm/vang) gene have been implicated in patterning and morphogenesis during gastrulation. Recent work shows that stbm/vang is mutated in zebrafish trilobite mutants and that stbm/vang is required for morphogenesis but not patterning during zebrafish gastrulation. AU - Heisenberg, Carl-Philipp J ID - 4207 IS - 19 JF - Current Biology SN - 0960-9822 TI - Wnt signalling: Refocusing on Strabismus VL - 12 ER - TY - JOUR AB - Cells at the anterior boundary of the neural plate (ANB) can induce telencephalic gene expression when transplanted to more posterior regions. Here, we identify a secreted Frizzled-related Wnt antagonist, Tic, that is expressed in ANB cells and can cell nonautonomously promote telencephalic gene expression in a concentration-dependent manner. Moreover, abrogation of Tlc function compromises telencephalic development. We also identify Wnt8b as a locally acting modulator of regional fate in the anterior neural plate and a likely target for antagonism by Tic. Finally, we show that tlc expression is regulated by signals that establish early antero-posterior and dorso-ventral ectodermal pattern. From these studies, we propose that local antagonism of Wnt activity within the anterior ectoderm is required to establish the telencephalon. AU - Houart, Corinne AU - Caneparo, Luca AU - Heisenberg, Carl-Philipp J AU - Barth, K Anukampa AU - Take Uchi, Masaya AU - Wilson, Stephen ID - 4194 IS - 2 JF - Neuron SN - 0896-6273 TI - Establishment of the telencephalon during gastrulation by local antagonism of Wnt signaling VL - 35 ER - TY - JOUR AB - Members of the Wnt family have been implicated in a variety of developmental processes including axis formation, Patterning of the central nervous system and tissue morphogenesis. Recent studies have shown that a Wnt signalling pathway similar to that involved in the establishment of planar cell polarity in Drosophila regulates convergent extension movements during zebrafish and Xenopus gastrulation. This finding provides a good starting point to dissect the complex cell biology and genetic regulation of vertebrate gastrulation movements. AU - Tada, Masazumi AU - Concha, Miguel AU - Heisenberg, Carl-Philipp J ID - 4148 IS - 3 JF - Seminars in Cell & Developmental Biology SN - 1084-9521 TI - Non-canonical Wnt signalling and regulation of gastrulation movements VL - 13 ER - TY - JOUR AB - During vertebrate gastrulation, large cellular rearrangements lead to the formation of the three germ layers, ectoderm, mesoderm and endoderm. Zebrafish offer many genetic and experimental advantages for studying vertebrate gastrulation movements. For instance, several mutants, including silberblick, knypek and trilobite, exhibit defects in morphogenesis during gastrulation. The identification of the genes mutated in these lines together with the analysis of the mutant phenotypes has provided new insights into the molecular and cellular mechanisms that underlie vertebrate gastrulation movements. AU - Heisenberg, Carl-Philipp J AU - Tada, Masazumi ID - 4196 IS - 6 JF - Seminars in Cell & Developmental Biology SN - 1084-9521 TI - Zebrafish gastrulation movements: bridging cell and developmental biology VL - 13 ER - TY - JOUR AB - Recent studies on vertebrate homologues of the van gogh/strabismus (vang/stbm) gene, a key player in planar cell polarity signalling in Drosophila, show that vang/stbm is involved in patterning and morphogenesis during vertebrate gastrulation where it modulates two distinct Wnt signals. AU - Heisenberg, Carl-Philipp J AU - Tada, Masazumi ID - 4199 IS - 4 JF - Current Biology SN - 0960-9822 TI - Wnt signalling: A moving picture emerges from van gogh VL - 12 ER - TY - JOUR AB - Pilot studies in England by Stopka and Macdonald revealed that allogrooming in the Old World wood mouse, Apodemus sylvaticus, is a commodity that males can trade for reproductive benefits with females. This study, which used a combination of field study and observations in experimental enclosures, revealed that specific experimental conditions such as group-size and sex-ratio manipulations have a significant effect on the pattern of allogrooming exchanged between individuals. Furthermore, females from the Czech population were more likely to associate with each other as revealed by the clustering of activity centers of females (i.e., as opposed to almost exclusive ranges in English populations), and also by the higher intensity of allogrooming exchanged between females (i.e., virtually lacking in the previous experiment with English mice). Therefore, geographic variation and specific social conditions seem to be important driving factors for allogrooming behavior. Together with changes in overall grooming patterns, allogrooming between males and females remained invariably asymmetrical over all four experimental groups (i.e., two conditions for each sex) in that males provided more allogrooming to females than they received from them. AU - Polechova, Jitka AU - Stopka, P. ID - 4139 IS - 8 JF - Canadian Journal of Zoology SN - 0008-4301 TI - Geometry of social relationships in the Old World wood mouse, Apodemus sylvaticus VL - 80 ER - TY - CONF AB - The writhing number measures the global geometry of a closed space curve or knot. We show that this measure is related to the average winding number of its Gauss map. Using this relationship, we give an algorithm for computing the writhing number for a polygonal knot with n edges in time roughly proportional to n(1.6). We also implement a different, simple algorithm and provide experimental evidence for its practical efficiency. AU - Agarwal, Pankaj AU - Edelsbrunner, Herbert AU - Wang, Yusu ID - 4003 SN - 9780898715132 T2 - Proceedings of the 13th annual ACM-SIAM symposium on Discrete algorithms TI - Computing the writhing number of a polygonal knot ER - TY - JOUR AB - This article is a survey of research areas in which motion plays a pivotal role. The aim of the article is to review current approaches to modeling motion together with related data structures and algorithms, and to summarize the challenges that lie ahead in producing a more unified theory of motion representation that would be useful across several disciplines. AU - Agarwal, Pankaj AU - Guibas, Leonidas AU - Edelsbrunner, Herbert AU - Erickson, Jeff AU - Isard, Michael AU - Har Peled, Sariel AU - Hershberger, John AU - Jensen, Christian AU - Kavraki, Lydia AU - Koehl, Patrice AU - Lin, Ming AU - Manocha, Dinesh AU - Metaxas, Dimitris AU - Mirtich, Brian AU - Mount, David AU - Muthukrishnan, Sankara AU - Pai, Dinesh AU - Sacks, Elisha AU - Snoeyink, Jack AU - Suri, Subhash AU - Wolefson, Ouri ID - 3995 IS - 4 JF - ACM Computing Surveys SN - 0360-0300 TI - Algorithmic issues in modeling motion VL - 34 ER - TY - JOUR AB - We present fast implementations of a hybrid algorithm for reporting box and cube intersections. Our algorithm initially takes a divide-and-conquer approach and switches to simpler algorithms for low numbers of boxes. We use our implementations as engines to solve problems about geometric primitives. We look at two such problems in the category of quality analysis of surface triangulations. AU - Zomorodian, Afra AU - Edelsbrunner, Herbert ID - 4000 IS - 1-2 JF - International Journal of Computational Geometry and Applications SN - 0218-1959 TI - Fast software for box intersections VL - 12 ER - TY - JOUR AB - We present results on a two-step improvement of mesh quality in three-dimensional Delaunay triangulations. The first step refines the triangulation by inserting sinks and eliminates tetrahedra with large circumradius over shortest edge length ratio. The second step assigns weights to the vertices to eliminate slivers. Our experimental findings provide evidence for the practical effectiveness of sliver exudation. AU - Edelsbrunner, Herbert AU - Guoy, Damrong ID - 3998 IS - 3 JF - Engineering with Computers SN - 0177-0667 TI - An experimental study of sliver exudation VL - 18 ER - TY - JOUR AB - The presynaptic Ca2+ signal is a key determinant of transmitter release at chemical synapses. In cortical synaptic terminals, however, little is known about the kinetic properties of the presynaptic Ca2+ channels. To investigate the timing and magnitude of the presynaptic Ca2+ inflow, we performed whole-cell patch-clamp recordings from mossy fiber boutons (MFBs) in rat hippocampus. MFBs showed large high-voltage-activated Ca(2+) currents, with a maximal amplitude of approximately 100 pA at a membrane potential of 0 mV. Both activation and deactivation were fast, with time constants in the submillisecond range at a temperature of approximately 23 degrees C. An MFB action potential (AP) applied as a voltage-clamp command evoked a transient Ca2+ current with an average amplitude of approximately 170 pA and a half-duration of 580 microsec. A prepulse to +40 mV had only minimal effects on the AP-evoked Ca2+ current, indicating that presynaptic APs open the voltage-gated Ca2+ channels very effectively. On the basis of the experimental data, we developed a kinetic model with four closed states and one open state, linked by voltage-dependent rate constants. Simulations of the Ca2+ current could reproduce the experimental data, including the large amplitude and rapid time course of the current evoked by MFB APs. Furthermore, the simulations indicate that the shape of the presynaptic AP and the gating kinetics of the Ca2+ channels are tuned to produce a maximal Ca2+ influx during a minimal period of time. The precise timing and high efficacy of Ca2+ channel activation at this cortical glutamatergic synapse may be important for synchronous transmitter release and temporal information processing. AU - Bischofberger, Josef AU - Geiger, Jörg AU - Jonas, Peter M ID - 3802 IS - 24 JF - Journal of Neuroscience SN - 0270-6474 TI - Timing and efficacy of Ca(2+) channel activation in hippocampal mossy fiber boutons VL - 22 ER - TY - JOUR AB - Hamilton's concept of local mate competition (LMC) is the standard model to explain female-biased sex ratios in solitary Hymenoptera. In social Hymenoptera, however, LMC has remained controversial, mainly because manipulation of sex allocation by workers in response to relatedness asymmetries is an additional powerful mechanism of female bias. Furthermore, the predominant mating systems in the social insects are thought to make LMC unlikely. Nevertheless, several species exist in which dispersal of males is limited and mating occurs in the nest. Some of these species, such as the ant Cardiocondyla obscurior, have evolved dimorphic males, with one morph being specialized for dispersal and the other for fighting with nest-mate males over access to females. Such life history, combining sociality and alternative reproductive tactics in males, provides a unique opportunity to test the power of LMC as a selective force leading to female-biased sex ratios in social Hymenoptera. We show that, in concordance with LMC predictions, an experimental increase in queen number leads to a shift in sex allocation in favour of non-dispersing males, but does not influence the proportion of disperser males. Furthermore, we can assign this change in sex allocation at the colony level to the queens and rule out worker manipulation. AU - Cremer, Sylvia AU - Heinze, Jürgen ID - 3919 IS - 1489 JF - Proceedings of the Royal Society of London Series B Biological Sciences SN - 0962-8452 TI - Adaptive production of fighter males: queens of the ant Cardiocondyla adjust the sex ratio under local mate competition VL - 269 ER -