TY - JOUR
AB - This paper presents a method for computing topology changes for triangle meshes in an interactive geometric modeling environment. Most triangle meshes in practice do not exhibit desirable geometric properties, so we develop a solution that is independent of standard assumptions and robust to geometric errors. Specifically, we provide the first method for topology change applicable to arbitrary non-solid, non-manifold, non-closed, self-intersecting surfaces. We prove that this new method for topology change produces the expected conventional results when applied to solid (closed, manifold, non-self-intersecting) surfaces---that is, we prove a backwards-compatibility property relative to prior work. Beyond solid surfaces, we present empirical evidence that our method remains tolerant to a variety of surface aberrations through the incorporation of a novel error correction scheme. Finally, we demonstrate how topology change applied to non-solid objects enables wholly new and useful behaviors.
AU - Bernstein, Gilbert
AU - Wojtan, Christopher J
ID - 2467
IS - 4
JF - ACM Transactions on Graphics
TI - Putting holes in holey geometry: Topology change for arbitrary surfaces
VL - 32
ER -
TY - JOUR
AB - Our work concerns the combination of an Eulerian liquid simulation with a high-resolution surface tracker (e.g. the level set method or a Lagrangian triangle mesh). The naive application of a high-resolution surface tracker to a low-resolution velocity field can produce many visually disturbing physical and topological artifacts that limit their use in practice. We address these problems by defining an error function which compares the current state of the surface tracker to the set of physically valid surface states. By reducing this error with a gradient descent technique, we introduce a novel physics-based surface fairing method. Similarly, by treating this error function as a potential energy, we derive a new surface correction force that mimics the vortex sheet equations. We demonstrate our results with both level set and mesh-based surface trackers.
AU - Bojsen-Hansen, Morten
AU - Wojtan, Christopher J
ID - 2468
IS - 4
JF - ACM Transactions on Graphics
TI - Liquid surface tracking with error compensation
VL - 32
ER -
TY - JOUR
AB - Cadherins are transmembrane proteins that mediate cell–cell adhesion in animals. By regulating contact formation and stability, cadherins play a crucial role in tissue morphogenesis and homeostasis. Here, we review the three major unctions of cadherins in cell–cell contact formation and stability. Two of those functions lead to a decrease in interfacial ension at the forming cell–cell contact, thereby promoting contact expansion — first, by providing adhesion tension that lowers interfacial tension at the cell–cell contact, and second, by signaling to the actomyosin cytoskeleton in order to reduce cortex tension and thus interfacial tension at the contact. The third function of cadherins in cell–cell contact formation is to stabilize the contact by resisting mechanical forces that pull on the contact.
AU - Maître, Jean-Léon
AU - Heisenberg, Carl-Philipp J
ID - 2469
IS - 14
JF - Current Biology
TI - Three functions of cadherins in cell adhesion
VL - 23
ER -
TY - JOUR
AB - Background:Auxin binding protein 1 (ABP1) is a putative auxin receptor and its function is indispensable for plant growth and development. ABP1 has been shown to be involved in auxin-dependent regulation of cell division and expansion, in plasma-membrane-related processes such as changes in transmembrane potential, and in the regulation of clathrin-dependent endocytosis. However, the ABP1-regulated downstream pathway remains elusive.Methodology/Principal Findings:Using auxin transport assays and quantitative analysis of cellular morphology we show that ABP1 regulates auxin efflux from tobacco BY-2 cells. The overexpression of ABP1can counterbalance increased auxin efflux and auxin starvation phenotypes caused by the overexpression of PIN auxin efflux carrier. Relevant mechanism involves the ABP1-controlled vesicle trafficking processes, including positive regulation of endocytosis of PIN auxin efflux carriers, as indicated by fluorescence recovery after photobleaching (FRAP) and pharmacological manipulations.Conclusions/Significance:The findings indicate the involvement of ABP1 in control of rate of auxin transport across plasma membrane emphasizing the role of ABP1 in regulation of PIN activity at the plasma membrane, and highlighting the relevance of ABP1 for the formation of developmentally important, PIN-dependent auxin gradients.
AU - Čovanová, Milada
AU - Sauer, Michael
AU - Rychtář, Jan
AU - Friml, Jirí
AU - Petrášek, Jan
AU - Zažímalová, Eva
ID - 2470
IS - 7
JF - PLoS One
TI - Overexpression of the auxin binding PROTEIN1 modulates PIN-dependent auxin transport in tobacco cells
VL - 8
ER -
TY - JOUR
AB - The impact of disulfide bonds on protein stability goes beyond simple equilibrium thermodynamics effects associated with the conformational entropy of the unfolded state. Indeed, disulfide crosslinks may play a role in the prevention of dysfunctional association and strongly affect the rates of irreversible enzyme inactivation, highly relevant in biotechnological applications. While these kinetic-stability effects remain poorly understood, by analogy with proposed mechanisms for processes of protein aggregation and fibrillogenesis, we propose that they may be determined by the properties of sparsely-populated, partially-unfolded intermediates. Here we report the successful design, on the basis of high temperature molecular-dynamics simulations, of six thermodynamically and kinetically stabilized variants of phytase from Citrobacter braakii (a biotechnologically important enzyme) with one, two or three engineered disulfides. Activity measurements and 3D crystal structure determination demonstrate that the engineered crosslinks do not cause dramatic alterations in the native structure. The inactivation kinetics for all the variants displays a strongly non-Arrhenius temperature dependence, with the time-scale for the irreversible denaturation process reaching a minimum at a given temperature within the range of the denaturation transition. We show this striking feature to be a signature of a key role played by a partially unfolded, intermediate state/ensemble. Energetic and mutational analyses confirm that the intermediate is highly unfolded (akin to a proposed critical intermediate in the misfolding of the prion protein), a result that explains the observed kinetic stabilization. Our results provide a rationale for the kinetic-stability consequences of disulfide-crosslink engineering and an experimental methodology to arrive at energetic/structural descriptions of the sparsely populated and elusive intermediates that play key roles in irreversible protein denaturation.
AU - Sanchez Romero, Inmaculada
AU - Ariza, Antonio
AU - Wilson, Keith
AU - Skjøt, Michael
AU - Vind, Jesper
AU - De Maria, Leonardo
AU - Skov, Lars
AU - Sánchez Ruiz, Jose
ID - 2471
IS - 7
JF - PLoS One
TI - Mechanism of protein kinetic stabilization by engineered disulfide crosslinks
VL - 8
ER -
TY - JOUR
AB - Plant-specific PIN-formed (PIN) efflux transporters for the plant hormone auxin are required for tissue-specific directional auxin transport and cellular auxin homeostasis. The Arabidopsis PIN protein family has been shown to play important roles in developmental processes such as embryogenesis, organogenesis, vascular tissue differentiation, root meristem patterning and tropic growth. Here we analyzed roles of the less characterised Arabidopsis PIN6 auxin transporter. PIN6 is auxin-inducible and is expressed during multiple auxin-regulated developmental processes. Loss of pin6 function interfered with primary root growth and lateral root development. Misexpression of PIN6 affected auxin transport and interfered with auxin homeostasis in other growth processes such as shoot apical dominance, lateral root primordia development, adventitious root formation, root hair outgrowth and root waving. These changes in auxin-regulated growth correlated with a reduction in total auxin transport as well as with an altered activity of DR5-GUS auxin response reporter. Overall, the data indicate that PIN6 regulates auxin homeostasis during plant development.
AU - Cazzonelli, Christopher
AU - Vanstraelen, Marleen
AU - Simon, Sibu
AU - Yin, Kuide
AU - Carron Arthur, Ashley
AU - Nisar, Nazia
AU - Tarle, Gauri
AU - Cuttriss, Abby
AU - Searle, Iain
AU - Benková, Eva
AU - Mathesius, Ulrike
AU - Masle, Josette
AU - Friml, Jirí
AU - Pogson, Barry
ID - 2472
IS - 7
JF - PLoS One
TI - Role of the Arabidopsis PIN6 auxin transporter in auxin homeostasis and auxin-mediated development
VL - 8
ER -
TY - JOUR
AB - When a mutation with selective advantage s spreads through a panmictic population, it may cause two lineages at a linked locus to coalesce; the probability of coalescence is exp(−2rT), where T∼log(2Ns)/s is the time to fixation, N is the number of haploid individuals, and r is the recombination rate. Population structure delays fixation, and so weakens the effect of a selective sweep. However, favourable alleles spread through a spatially continuous population behind a narrow wavefront; ancestral lineages are confined at the tip of this front, and so coalesce rapidly. In extremely dense populations, coalescence is dominated by rare fluctuations ahead of the front. However, we show that for moderate densities, a simple quasi-deterministic approximation applies: the rate of coalescence within the front is λ∼2g(η)/(ρℓ), where ρ is the population density and is the characteristic scale of the wavefront; g(η) depends only on the strength of random drift, . The net effect of a sweep on coalescence also depends crucially on whether two lineages are ever both within the wavefront at the same time: even in the extreme case when coalescence within the front is instantaneous, the net rate of coalescence may be lower than in a single panmictic population. Sweeps can also have a substantial impact on the rate of gene flow. A single lineage will jump to a new location when it is hit by a sweep, with mean square displacement ; this can be substantial if the species’ range, L, is large, even if the species-wide rate of sweeps per map length, Λ/R, is small. This effect is half as strong in two dimensions. In contrast, the rate of coalescence between lineages, at random locations in space and on the genetic map, is proportional to (c/L)(Λ/R), where c is the wavespeed: thus, on average, one-dimensional structure is likely to reduce coalescence due to sweeps, relative to panmixis. In two dimensions, genes must move along the front before they can coalesce; this process is rapid, being dominated by rare fluctuations. This leads to a dramatically higher rate of coalescence within the wavefront than if lineages simply diffused along the front. Nevertheless, the net rate of coalescence due to a sweep through a two-dimensional population is likely to be lower than it would be with panmixis.
AU - Barton, Nicholas H
AU - Etheridge, Alison
AU - Kelleher, Jerome
AU - Véber, Amandine
ID - 2473
IS - 8
JF - Theoretical Population Biology
TI - Genetic hitch-hiking in spatially extended populations
VL - 87
ER -
TY - JOUR
AB - We study the problem of object recognition for categories for which we have no training examples, a task also called zero-data or zero-shot learning. This situation has hardly been studied in computer vision research, even though it occurs frequently: the world contains tens of thousands of different object classes and for only few of them image collections have been formed and suitably annotated. To tackle the problem we introduce attribute-based classification: objects are identified based on a high-level description that is phrased in terms of semantic attributes, such as the object's color or shape. Because the identification of each such property transcends the specific learning task at hand, the attribute classifiers can be pre-learned independently, e.g. from existing image datasets unrelated to the current task. Afterwards, new classes can be detected based on their attribute representation, without the need for a new training phase. In this paper we also introduce a new dataset, Animals with Attributes, of over 30,000 images of 50 animal classes, annotated with 85 semantic attributes. Extensive experiments on this and two more datasets show that attribute-based classification indeed is able to categorize images without access to any training images of the target classes.
AU - Lampert, Christoph
AU - Nickisch, Hannes
AU - Harmeling, Stefan
ID - 2516
IS - 3
JF - IEEE Transactions on Pattern Analysis and Machine Intelligence
TI - Attribute-based classification for zero-shot learning of object categories
VL - 36
ER -
TY - CONF
AB - Traditional formal methods are based on a Boolean satisfaction notion: a reactive system satisfies, or not, a given specification. We generalize formal methods to also address the quality of systems. As an adequate specification formalism we introduce the linear temporal logic LTL[F]. The satisfaction value of an LTL[F] formula is a number between 0 and 1, describing the quality of the satisfaction. The logic generalizes traditional LTL by augmenting it with a (parameterized) set F of arbitrary functions over the interval [0,1]. For example, F may contain the maximum or minimum between the satisfaction values of subformulas, their product, and their average. The classical decision problems in formal methods, such as satisfiability, model checking, and synthesis, are generalized to search and optimization problems in the quantitative setting. For example, model checking asks for the quality in which a specification is satisfied, and synthesis returns a system satisfying the specification with the highest quality. Reasoning about quality gives rise to other natural questions, like the distance between specifications. We formalize these basic questions and study them for LTL[F]. By extending the automata-theoretic approach for LTL to a setting that takes quality into an account, we are able to solve the above problems and show that reasoning about LTL[F] has roughly the same complexity as reasoning about traditional LTL.
AU - Almagor, Shaull
AU - Boker, Udi
AU - Kupferman, Orna
ID - 2517
IS - Part 2
TI - Formalizing and reasoning about quality
VL - 7966
ER -
TY - CONF
AB - A class of valued constraint satisfaction problems (VCSPs) is characterised by a valued constraint language, a fixed set of cost functions on a finite domain. An instance of the problem is specified by a sum of cost functions from the language with the goal to minimise the sum. We study which classes of finite-valued languages can be solved exactly by the basic linear programming relaxation (BLP). Thapper and Živný showed [20] that if BLP solves the language then the language admits a binary commutative fractional polymorphism. We prove that the converse is also true. This leads to a necessary and a sufficient condition which can be checked in polynomial time for a given language. In contrast, the previous necessary and sufficient condition due to [20] involved infinitely many inequalities. More recently, Thapper and Živný [21] showed (using, in particular, a technique introduced in this paper) that core languages that do not satisfy our condition are NP-hard. Taken together, these results imply that a finite-valued language can either be solved using Linear Programming or is NP-hard.
AU - Kolmogorov, Vladimir
ID - 2518
IS - 1
TI - The power of linear programming for finite-valued CSPs: A constructive characterization
VL - 7965
ER -
TY - CONF
AB - We propose a probabilistic model to infer supervised latent variables in
the Hamming space from observed data. Our model allows simultaneous
inference of the number of binary latent variables, and their values. The
latent variables preserve neighbourhood structure of the data in a sense
that objects in the same semantic concept have similar latent values, and
objects in different concepts have dissimilar latent values. We formulate
the supervised infinite latent variable problem based on an intuitive
principle of pulling objects together if they are of the same type, and
pushing them apart if they are not. We then combine this principle with a
flexible Indian Buffet Process prior on the latent variables. We show that
the inferred supervised latent variables can be directly used to perform a
nearest neighbour search for the purpose of retrieval. We introduce a new
application of dynamically extending hash codes, and show how to
effectively couple the structure of the hash codes with continuously
growing structure of the neighbourhood preserving infinite latent feature
space.
AU - Quadrianto, Novi
AU - Sharmanska, Viktoriia
AU - Knowles, David
AU - Ghahramani, Zoubin
ID - 2520
SN - 9780974903996
T2 - Proceedings of the 29th conference uncertainty in Artificial Intelligence
TI - The supervised IBP: Neighbourhood preserving infinite latent feature models
ER -
TY - CONF
AB - Even though both population and quantitative genetics, and evolutionary computation, deal with the same questions, they have developed largely independently of each other. I review key results from each field, emphasising those that apply independently of the (usually unknown) relation between genotype and phenotype. The infinitesimal model provides a simple framework for predicting the response of complex traits to selection, which in biology has proved remarkably successful. This allows one to choose the schedule of population sizes and selection intensities that will maximise the response to selection, given that the total number of individuals realised, C = ∑t Nt, is constrained. This argument shows that for an additive trait (i.e., determined by the sum of effects of the genes), the optimum population size and the maximum possible response (i.e., the total change in trait mean) are both proportional to √C.
AU - Barton, Nicholas H
AU - Paixao, Tiago
ID - 2718
T2 - Proceedings of the 15th annual conference on Genetic and evolutionary computation
TI - Can quantitative and population genetics help us understand evolutionary computation?
ER -
TY - CONF
AB - Prediction of the evolutionary process is a long standing problem both in the theory of evolutionary biology and evolutionary computation (EC). It has long been realized that heritable variation is crucial to both the response to selection and the success of genetic algorithms. However, not all variation contributes in the same way to the response. Quantitative genetics has developed a large body of work trying to estimate and understand how different components of the variance in fitness in the population contribute to the response to selection. We illustrate how to apply some concepts of quantitative genetics to the analysis of genetic algorithms. In particular, we derive estimates for the short term prediction of the response to selection and we use variance decomposition to gain insight on local aspects of the landscape. Finally, we propose a new population based genetic algorithm that uses these methods to improve its operation.
AU - Paixao, Tiago
AU - Barton, Nicholas H
ID - 2719
T2 - Proceedings of the 15th annual conference on Genetic and evolutionary computation
TI - A variance decomposition approach to the analysis of genetic algorithms
ER -
TY - JOUR
AB - Knowledge of the rate and fitness effects of mutations is essential for understanding the process of evolution. Mutations are inherently difficult to study because they are rare and are frequently eliminated by natural selection. In the ciliate Tetrahymena thermophila, mutations can accumulate in the germline genome without being exposed to selection. We have conducted a mutation accumulation (MA) experiment in this species. Assuming that all mutations are deleterious and have the same effect, we estimate that the deleterious mutation rate per haploid germline genome per generation is U = 0.0047 (95% credible interval: 0.0015, 0.0125), and that germline mutations decrease fitness by s = 11% when expressed in a homozygous state (95% CI: 4.4%, 27%). We also estimate that deleterious mutations are partially recessive on average (h = 0.26; 95% CI: –0.022, 0.62) and that the rate of lethal mutations is <10% of the deleterious mutation rate. Comparisons between the observed evolutionary responses in the germline and somatic genomes and the results from individual-based simulations of MA suggest that the two genomes have similar mutational parameters. These are the first estimates of the deleterious mutation rate and fitness effects from the eukaryotic supergroup Chromalveolata and are within the range of those of other eukaryotes.
AU - Long, Hongan
AU - Paixao, Tiago
AU - Azevedo, Ricardo
AU - Zufall, Rebecca
ID - 2720
IS - 2
JF - Genetics
TI - Accumulation of spontaneous mutations in the ciliate Tetrahymena thermophila
VL - 195
ER -
TY - JOUR
AB - We consider non-interacting particles subject to a fixed external potential V and a self-generated magnetic field B. The total energy includes the field energy β∫B2 and we minimize over all particle states and magnetic fields. In the case of spin-1/2 particles this minimization leads to the coupled Maxwell-Pauli system. The parameter β tunes the coupling strength between the field and the particles and it effectively determines the strength of the field. We investigate the stability and the semiclassical asymptotics, h→0, of the total ground state energy E(β,h,V). The relevant parameter measuring the field strength in the semiclassical limit is κ=βh. We are not able to give the exact leading order semiclassical asymptotics uniformly in κ or even for fixed κ. We do however give upper and lower bounds on E with almost matching dependence on κ. In the simultaneous limit h→0 and κ→∞ we show that the standard non-magnetic Weyl asymptotics holds. The same result also holds for the spinless case, i.e. where the Pauli operator is replaced by the Schrödinger operator.
AU - Erdös, László
AU - Fournais, Søren
AU - Solovej, Jan
ID - 2698
IS - 6
JF - Journal of the European Mathematical Society
TI - Stability and semiclassics in self-generated fields
VL - 15
ER -
TY - JOUR
AB - We consider random n×n matrices of the form (XX*+YY*)^{-1/2}YY*(XX*+YY*)^{-1/2}, where X and Y have independent entries with zero mean and variance one. These matrices are the natural generalization of the Gaussian case, which are known as MANOVA matrices and which have joint eigenvalue density given by the third classical ensemble, the Jacobi ensemble. We show that, away from the spectral edge, the eigenvalue density converges to the limiting density of the Jacobi ensemble even on the shortest possible scales of order 1/n (up to log n factors). This result is the analogue of the local Wigner semicircle law and the local Marchenko-Pastur law for general MANOVA matrices.
AU - Erdös, László
AU - Farrell, Brendan
ID - 2782
IS - 6
JF - Journal of Statistical Physics
TI - Local eigenvalue density for general MANOVA matrices
VL - 152
ER -
TY - JOUR
AB - A novel Taylor-Couette system has been constructed for investigations of transitional as well as high Reynolds number turbulent flows in very large aspect ratios. The flexibility of the setup enables studies of a variety of problems regarding hydrodynamic instabilities and turbulence in rotating flows. The inner and outer cylinders and the top and bottom endplates can be rotated independently with rotation rates of up to 30 Hz, thereby covering five orders of magnitude in Reynolds numbers (Re = 101-106). The radius ratio can be easily changed, the highest realized one is η = 0.98 corresponding to an aspect ratio of 260 gap width in the vertical and 300 in the azimuthal direction. For η < 0.98 the aspect ratio can be dynamically changed during measurements and complete transparency in the radial direction over the full length of the cylinders is provided by the usage of a precision glass inner cylinder. The temperatures of both cylinders are controlled independently. Overall this apparatus combines an unmatched variety in geometry, rotation rates, and temperatures, which is provided by a sophisticated high-precision bearing system. Possible applications are accurate studies of the onset of turbulence and spatio-temporal intermittent flow patterns in very large domains, transport processes of turbulence at high Re, the stability of Keplerian flows for different boundary conditions, and studies of baroclinic instabilities.
AU - Avila, Kerstin
AU - Hof, Björn
ID - 2806
IS - 6
JF - Review of Scientific Instruments
TI - High-precision Taylor-Couette experiment to study subcritical transitions and the role of boundary conditions and size effects
VL - 84
ER -
TY - CONF
AB - We consider several basic problems of algebraic topology, with connections to combinatorial and geometric questions, from the point of view of computational complexity. The extension problem asks, given topological spaces X; Y , a subspace A ⊆ X, and a (continuous) map f : A → Y , whether f can be extended to a map X → Y . For computational purposes, we assume that X and Y are represented as finite simplicial complexes, A is a subcomplex of X, and f is given as a simplicial map. In this generality the problem is undecidable, as follows from Novikov's result from the 1950s on uncomputability of the fundamental group π1(Y ). We thus study the problem under the assumption that, for some k ≥ 2, Y is (k - 1)-connected; informally, this means that Y has \no holes up to dimension k-1" (a basic example of such a Y is the sphere Sk). We prove that, on the one hand, this problem is still undecidable for dimX = 2k. On the other hand, for every fixed k ≥ 2, we obtain an algorithm that solves the extension problem in polynomial time assuming Y (k - 1)-connected and dimX ≤ 2k - 1. For dimX ≤ 2k - 2, the algorithm also provides a classification of all extensions up to homotopy (continuous deformation). This relies on results of our SODA 2012 paper, and the main new ingredient is a machinery of objects with polynomial-time homology, which is a polynomial-time analog of objects with effective homology developed earlier by Sergeraert et al. We also consider the computation of the higher homotopy groups πk(Y ), k ≥ 2, for a 1-connected Y . Their computability was established by Brown in 1957; we show that πk(Y ) can be computed in polynomial time for every fixed k ≥ 2. On the other hand, Anick proved in 1989 that computing πk(Y ) is #P-hard if k is a part of input, where Y is a cell complex with certain rather compact encoding. We strengthen his result to #P-hardness for Y given as a simplicial complex.
AU - Čadek, Martin
AU - Krcál, Marek
AU - Matoušek, Jiří
AU - Vokřínek, Lukáš
AU - Wagner, Uli
ID - 2807
T2 - 45th Annual ACM Symposium on theory of computing
TI - Extending continuous maps: Polynomiality and undecidability
ER -
TY - JOUR
AB - In order to establish a reference for analysis of the function of auxin and the auxin biosynthesis regulators SHORT INTERNODE/ STYLISH (SHI/STY) during Physcomitrella patens reproductive development, we have described male (antheridial) and female (archegonial) development in detail, including temporal and positional information of organ initiation. This has allowed us to define discrete stages of organ morphogenesis and to show that reproductive organ development in P. patens is highly organized and that organ phyllotaxis differs between vegetative and reproductive development. Using the PpSHI1 and PpSHI2 reporter and knockout lines, the auxin reporters GmGH3pro:GUS and PpPINApro:GFP-GUS, and the auxin-conjugating transgene PpSHI2pro:IAAL, we could show that the PpSHI genes, and by inference also auxin, play important roles for reproductive organ development in moss. The PpSHI genes are required for the apical opening of the reproductive organs, the final differentiation of the egg cell, and the progression of canal cells into a cell death program. The apical cells of the archegonium, the canal cells, and the egg cell are also sites of auxin responsiveness and are affected by reduced levels of active auxin, suggesting that auxin mediates PpSHI function in the reproductive organs.
AU - Landberg, Katarina
AU - Pederson, Eric
AU - Viaene, Tom
AU - Bozorg, Behruz
AU - Friml, Jirí
AU - Jönsson, Henrik
AU - Thelander, Mattias
AU - Sundberg, Eva
ID - 2808
IS - 3
JF - Plant Physiology
TI - The moss physcomitrella patens reproductive organ development is highly organized, affected by the two SHI/STY genes and by the level of active auxin in the SHI/STY expression domain
VL - 162
ER -
TY - JOUR
AB - The epistatic interactions that underlie evolutionary constraint have mainly been studied for constant external conditions. However, environmental changes may modulate epistasis and hence affect genetic constraints. Here we investigate genetic constraints in the adaptive evolution of a novel regulatory function in variable environments, using the lac repressor, LacI, as a model system. We have systematically reconstructed mutational trajectories from wild type LacI to three different variants that each exhibit an inverse response to the inducing ligand IPTG, and analyzed the higher-order interactions between genetic and environmental changes. We find epistasis to depend strongly on the environment. As a result, mutational steps essential to inversion but inaccessible by positive selection in one environment, become accessible in another. We present a graphical method to analyze the observed complex higher-order interactions between multiple mutations and environmental change, and show how the interactions can be explained by a combination of mutational effects on allostery and thermodynamic stability. This dependency of genetic constraint on the environment should fundamentally affect evolutionary dynamics and affects the interpretation of phylogenetic data.
AU - De Vos, Marjon
AU - Poelwijk, Frank
AU - Battich, Nico
AU - Ndika, Joseph
AU - Tans, Sander
ID - 2810
IS - 6
JF - PLoS Genetics
TI - Environmental dependence of genetic constraint
VL - 9
ER -