@article{4231, abstract = {The evolution of quantitative characters depends on the frequencies of the alleles involved, yet these frequencies cannot usually be measured. Previous groups have proposed an approximation to the dynamics of quantitative traits, based on an analogy with statistical mechanics. We present a modified version of that approach, which makes the analogy more precise and applies quite generally to describe the evolution of allele frequencies. We calculate explicitly how the macroscopic quantities (i.e., quantities that depend on the quantitative trait) depend on evolutionary forces, in a way that is independent of the microscopic details. We first show that the stationary distribution of allele frequencies under drift, selection, and mutation maximizes a certain measure of entropy, subject to constraints on the expectation of observable quantities. We then approximate the dynamical changes in these expectations, assuming that the distribution of allele frequencies always maximizes entropy, conditional on the expected values. When applied to directional selection on an additive trait, this gives a very good approximation to the evolution of the trait mean and the genetic variance, when the number of mutations per generation is sufficiently high (4Nμ > 1). We show how the method can be modified for small mutation rates (4Nμ → 0). We outline how this method describes epistatic interactions as, for example, with stabilizing selection.}, author = {Barton, Nicholas H and De Vladar, Harold}, journal = {Genetics}, number = {3}, pages = {997 -- 1011}, publisher = {Genetics Society of America}, title = {{Statistical mechanics and the evolution of polygenic quantitative traits}}, doi = {10.1534/genetics.108.099309}, volume = {181}, year = {2009}, } @article{4242, abstract = {Felsenstein distinguished two ways by which selection can directly strengthen isolation. First, a modifier that strengthens prezygotic isolation can be favored everywhere. This fits with the traditional view of reinforcement as an adaptation to reduce deleterious hybridization by strengthening assortative mating. Second, selection can favor association between different incompatibilities, despite recombination. We generalize this “two allele” model to follow associations among any number of incompatibilities, which may include both assortment and hybrid inviability. Our key argument is that this process, of coupling between incompatibilities, may be quite different from the usual view of reinforcement: strong isolation can evolve through the coupling of any kind of incompatibility, whether prezygotic or postzygotic. Single locus incompatibilities become coupled because associations between them increase the variance in compatibility, which in turn increases mean fitness if there is positive epistasis. Multiple incompatibilities, each maintained by epistasis, can become coupled in the same way. In contrast, a single-locus incompatibility can become coupled with loci that reduce the viability of haploid hybrids because this reduces harmful recombination. We obtain simple approximations for the limits of tight linkage, and strong assortment, and show how assortment alleles can invade through associations with other components of reproductive isolation.}, author = {Barton, Nicholas H and De Cara, Maria}, journal = {Evolution; International Journal of Organic Evolution}, number = {5}, pages = {1171 -- 1190}, publisher = {Wiley}, title = {{The evolution of strong reproductive isolation}}, doi = {10.1111/j.1558-5646.2009.00622.x}, volume = {63}, year = {2009}, } @inproceedings{4542, abstract = {Weighted automata are finite automata with numerical weights on transitions. Nondeterministic weighted automata define quantitative languages L that assign to each word w a real number L(w) computed as the maximal value of all runs over w, and the value of a run r is a function of the sequence of weights that appear along r. There are several natural functions to consider such as Sup, LimSup, LimInf, limit average, and discounted sum of transition weights. We introduce alternating weighted automata in which the transitions of the runs are chosen by two players in a turn-based fashion. Each word is assigned the maximal value of a run that the first player can enforce regardless of the choices made by the second player. We survey the results about closure properties, expressiveness, and decision problems for nondeterministic weighted automata, and we extend these results to alternating weighted automata. For quantitative languages L 1 and L 2, we consider the pointwise operations max(L 1,L 2), min(L 1,L 2), 1 − L 1, and the sum L 1 + L 2. We establish the closure properties of all classes of alternating weighted automata with respect to these four operations. We next compare the expressive power of the various classes of alternating and nondeterministic weighted automata over infinite words. In particular, for limit average and discounted sum, we show that alternation brings more expressive power than nondeterminism. Finally, we present decidability results and open questions for the quantitative extension of the classical decision problems in automata theory: emptiness, universality, language inclusion, and language equivalence.}, author = {Chatterjee, Krishnendu and Doyen, Laurent and Henzinger, Thomas A}, location = {Wroclaw, Poland}, pages = {3 -- 13}, publisher = {Springer}, title = {{Alternating weighted automata}}, doi = {10.1007/978-3-642-03409-1_2}, volume = {5699}, year = {2009}, } @inproceedings{4543, abstract = {The synthesis of a reactive system with respect to all omega-regular specification requires the solution of a graph game. Such games have been extended in two natural ways. First, a game graph can be equipped with probabilistic choices between alternative transitions, thus allowing the, modeling of uncertain behaviour. These are called stochastic games. Second, a liveness specification can he strengthened to require satisfaction within all unknown but bounded amount of time. These are called finitary objectives. We study. for the first time, the, combination of Stochastic games and finitary objectives. We characterize the requirements on optimal strategies and provide algorithms for Computing the maximal achievable probability of winning stochastic games with finitary parity or Street, objectives. Most notably the set of state's from which a player can win with probability . for a finitary parity objective can he computed in polynomial time even though no polynomial-time algorithm is known in the nonfinitary case.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Horn, Florian}, location = {High Tatras, Slovakia}, pages = {34 -- 54}, publisher = {Springer}, title = {{Stochastic games with finitary objectives}}, doi = {10.1007/978-3-642-03816-7_4}, volume = {5734}, year = {2009}, } @inproceedings{4545, abstract = {A stochastic game is a two-player game played oil a graph, where in each state the successor is chosen either by One of the players, or according to a probability distribution. We Survey Stochastic games with limsup and liminf objectives. A real-valued re-ward is assigned to each state, and the value of all infinite path is the limsup (resp. liminf) of all rewards along the path. The value of a stochastic game is the maximal expected value of an infinite path that call he achieved by resolving the decisions of the first player. We present the complexity of computing values of Stochastic games and their subclasses, and the complexity, of optimal strategies in such games. }, author = {Chatterjee, Krishnendu and Doyen, Laurent and Henzinger, Thomas A}, location = {Rhodos, Greece}, pages = {1 -- 15}, publisher = {Springer}, title = {{A survey of stochastic games with limsup and liminf objectives}}, doi = {10.1007/978-3-642-02930-1_1}, volume = {5556}, year = {2009}, } @inproceedings{4569, abstract = {Most specification languages express only qualitative constraints. However, among two implementations that satisfy a given specification, one may be preferred to another. For example, if a specification asks that every request is followed by a response, one may prefer an implementation that generates responses quickly but does not generate unnecessary responses. We use quantitative properties to measure the “goodness” of an implementation. Using games with corresponding quantitative objectives, we can synthesize “optimal” implementations, which are preferred among the set of possible implementations that satisfy a given specification. In particular, we show how automata with lexicographic mean-payoff conditions can be used to express many interesting quantitative properties for reactive systems. In this framework, the synthesis of optimal implementations requires the solution of lexicographic mean-payoff games (for safety requirements), and the solution of games with both lexicographic mean-payoff and parity objectives (for liveness requirements). We present algorithms for solving both kinds of novel graph games.}, author = {Bloem, Roderick and Chatterjee, Krishnendu and Henzinger, Thomas A and Jobstmann, Barbara}, location = {Grenoble, France}, pages = {140 -- 156}, publisher = {Springer}, title = {{Better quality in synthesis through quantitative objectives}}, doi = {10.1007/978-3-642-02658-4_14}, volume = {5643}, year = {2009}, } @article{9457, abstract = {Eukaryotic chromatin is separated into functional domains differentiated by posttranslational histone modifications, histone variants, and DNA methylation1–6. Methylation is associated with repression of transcriptional initiation in plants and animals, and is frequently found in transposable elements. Proper methylation patterns are critical for eukaryotic development4,5, and aberrant methylation-induced silencing of tumor suppressor genes is a common feature of human cancer7. In contrast to methylation, the histone variant H2A.Z is preferentially deposited by the Swr1 ATPase complex near 5′ ends of genes where it promotes transcriptional competence8–20. How DNA methylation and H2A.Z influence transcription remains largely unknown. Here we show that in the plant Arabidopsis thaliana, regions of DNA methylation are quantitatively deficient in H2A.Z. Exclusion of H2A.Z is seen at sites of DNA methylation in the bodies of actively transcribed genes and in methylated transposons. Mutation of the MET1 DNA methyltransferase, which causes both losses and gains of DNA methylation4,5, engenders opposite changes in H2A.Z deposition, while mutation of the PIE1 subunit of the Swr1 complex that deposits H2A.Z17 leads to genome-wide hypermethylation. Our findings indicate that DNA methylation can influence chromatin structure and effect gene silencing by excluding H2A.Z, and that H2A.Z protects genes from DNA methylation.}, author = {Zilberman, Daniel and Coleman-Derr, Devin and Ballinger, Tracy and Henikoff, Steven}, issn = {1476-4687}, journal = {Nature}, keywords = {Multidisciplinary}, number = {7218}, pages = {125--129}, publisher = {Springer Nature}, title = {{Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks}}, doi = {10.1038/nature07324}, volume = {456}, year = {2008}, } @article{9537, abstract = {DNA methylation is an ancient process found in all domains of life. Although the enzymes that mediate methylation have remained highly conserved, DNA methylation has been adapted for a variety of uses throughout evolution, including defense against transposable elements and control of gene expression. Defects in DNA methylation are linked to human diseases, including cancer. Methylation has been lost several times in the course of animal and fungal evolution, thus limiting the opportunity for study in common model organisms. In the past decade, plants have emerged as a premier model system for genetic dissection of DNA methylation. A recent combination of plant genetics with powerful genomic approaches has led to a number of exciting discoveries and promises many more.}, author = {Zilberman, Daniel}, issn = {1369-5266}, journal = {Current Opinion in Plant Biology}, number = {5}, pages = {554--559}, publisher = {Elsevier }, title = {{The evolving functions of DNA methylation}}, doi = {10.1016/j.pbi.2008.07.004}, volume = {11}, year = {2008}, } @article{517, author = {Barton, Nicholas H}, journal = {Genetics Research}, number = {5-6}, pages = {475 -- 477}, publisher = {Cambridge University Press}, title = {{Identity and coalescence in structured populations: A commentary on 'Inbreeding coefficients and coalescence times' by Montgomery Slatkin}}, doi = {10.1017/S0016672308009683}, volume = {89}, year = {2008}, } @article{12201, abstract = {The development of plant lateral organs is interesting because, although many of the same genes seem to be involved in the early growth of primordia, completely different gene combinations are required for the complete development of organs such as leaves and stamens. Thus, the genes common to the development of most organs, which generally form and polarize the primordial ‘envelope’, must at some stage interact with those that ‘install’ the functional content of the organ – in the case of the stamen, the four microsporangia. Although distinct genetic pathways of organ initiation, polarity establishment and setting up the reproductive cell line can readily be recognized, they do not occur sequentially. Rather, they are activated early and run in parallel. There is evidence for continuing crosstalk between these pathways.}, author = {Feng, Xiaoqi and Dickinson, Hugh G.}, issn = {0168-9525}, journal = {Trends in Genetics}, keywords = {Genetics}, number = {10}, pages = {503--510}, publisher = {Elsevier BV}, title = {{Packaging the male germline in plants}}, doi = {10.1016/j.tig.2007.08.005}, volume = {23}, year = {2007}, } @article{9487, abstract = {Cytosine DNA methylation is considered to be a stable epigenetic mark, but active demethylation has been observed in both plants and animals. In Arabidopsis thaliana, DNA glycosylases of the DEMETER (DME) family remove methylcytosines from DNA. Demethylation by DME is necessary for genomic imprinting, and demethylation by a related protein, REPRESSOR OF SILENCING1, prevents gene silencing in a transgenic background. However, the extent and function of demethylation by DEMETER-LIKE (DML) proteins in WT plants is not known. Using genome-tiling microarrays, we mapped DNA methylation in mutant and WT plants and identified 179 loci actively demethylated by DML enzymes. Mutations in DML genes lead to locus-specific DNA hypermethylation. Reintroducing WT DML genes restores most loci to the normal pattern of methylation, although at some loci, hypermethylated epialleles persist. Of loci demethylated by DML enzymes, >80% are near or overlap genes. Genic demethylation by DML enzymes primarily occurs at the 5′ and 3′ ends, a pattern opposite to the overall distribution of WT DNA methylation. Our results show that demethylation by DML DNA glycosylases edits the patterns of DNA methylation within the Arabidopsis genome to protect genes from potentially deleterious methylation.}, author = {Penterman, Jon and Zilberman, Daniel and Huh, Jin Hoe and Ballinger, Tracy and Henikoff, Steven and Fischer, Robert L.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {16}, pages = {6752--6757}, publisher = {National Academy of Sciences}, title = {{DNA demethylation in the Arabidopsis genome}}, doi = {10.1073/pnas.0701861104}, volume = {104}, year = {2007}, } @misc{9504, author = {Zilberman, Daniel}, booktitle = {Nature Genetics}, issn = {1546-1718}, number = {4}, pages = {442--443}, publisher = {Nature Publishing Group}, title = {{The human promoter methylome}}, doi = {10.1038/ng0407-442}, volume = {39}, year = {2007}, } @article{9524, abstract = {Cytosine methylation is the most common covalent modification of DNA in eukaryotes. DNA methylation has an important role in many aspects of biology, including development and disease. Methylation can be detected using bisulfite conversion, methylation-sensitive restriction enzymes, methyl-binding proteins and anti-methylcytosine antibodies. Combining these techniques with DNA microarrays and high-throughput sequencing has made the mapping of DNA methylation feasible on a genome-wide scale. Here we discuss recent developments and future directions for identifying and mapping methylation, in an effort to help colleagues to identify the approaches that best serve their research interests.}, author = {Zilberman, Daniel and Henikoff, Steven}, issn = {1477-9129}, journal = {Development}, number = {22}, pages = {3959--3965}, publisher = {The Company of Biologists}, title = {{Genome-wide analysis of DNA methylation patterns}}, doi = {10.1242/dev.001131}, volume = {134}, year = {2007}, } @article{9505, abstract = {Cytosine methylation, a common form of DNA modification that antagonizes transcription, is found at transposons and repeats in vertebrates, plants and fungi. Here we have mapped DNA methylation in the entire Arabidopsis thaliana genome at high resolution. DNA methylation covers transposons and is present within a large fraction of A. thaliana genes. Methylation within genes is conspicuously biased away from gene ends, suggesting a dependence on RNA polymerase transit. Genic methylation is strongly influenced by transcription: moderately transcribed genes are most likely to be methylated, whereas genes at either extreme are least likely. In turn, transcription is influenced by methylation: short methylated genes are poorly expressed, and loss of methylation in the body of a gene leads to enhanced transcription. Our results indicate that genic transcription and DNA methylation are closely interwoven processes.}, author = {Zilberman, Daniel and Gehring, Mary and Tran, Robert K. and Ballinger, Tracy and Henikoff, Steven}, issn = {1546-1718}, journal = {Nature Genetics}, number = {1}, pages = {61--69}, publisher = {Nature Publishing Group}, title = {{Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription}}, doi = {10.1038/ng1929}, volume = {39}, year = {2006}, } @article{9491, abstract = {Cytosine DNA methylation in vertebrates is widespread, but methylation in plants is found almost exclusively at transposable elements and repetitive DNA [1]. Within regions of methylation, methylcytosines are typically found in CG, CNG, and asymmetric contexts. CG sites are maintained by a plant homolog of mammalian Dnmt1 acting on hemi-methylated DNA after replication. Methylation of CNG and asymmetric sites appears to be maintained at each cell cycle by other mechanisms. We report a new type of DNA methylation in Arabidopsis, dense CG methylation clusters found at scattered sites throughout the genome. These clusters lack non-CG methylation and are preferentially found in genes, although they are relatively deficient toward the 5′ end. CG methylation clusters are present in lines derived from different accessions and in mutants that eliminate de novo methylation, indicating that CG methylation clusters are stably maintained at specific sites. Because 5-methylcytosine is mutagenic, the appearance of CG methylation clusters over evolutionary time predicts a genome-wide deficiency of CG dinucleotides and an excess of C(A/T)G trinucleotides within transcribed regions. This is exactly what we find, implying that CG methylation clusters have contributed profoundly to plant gene evolution. We suggest that CG methylation clusters silence cryptic promoters that arise sporadically within transcription units.}, author = {Tran, Robert K. and Henikoff, Jorja G. and Zilberman, Daniel and Ditt, Renata F. and Jacobsen, Steven E. and Henikoff, Steven}, issn = {1879-0445}, journal = {Current Biology}, number = {2}, pages = {154--159}, publisher = {Elsevier}, title = {{DNA methylation profiling identifies CG methylation clusters in Arabidopsis genes}}, doi = {10.1016/j.cub.2005.01.008}, volume = {15}, year = {2005}, } @article{9514, abstract = {Background: DNA methylation occurs at preferred sites in eukaryotes. In Arabidopsis, DNA cytosine methylation is maintained by three subfamilies of methyltransferases with distinct substrate specificities and different modes of action. Targeting of cytosine methylation at selected loci has been found to sometimes involve histone H3 methylation and small interfering (si)RNAs. However, the relationship between different cytosine methylation pathways and their preferred targets is not known. Results: We used a microarray-based profiling method to explore the involvement of Arabidopsis CMT3 and DRM DNA methyltransferases, a histone H3 lysine-9 methyltransferase (KYP) and an Argonaute-related siRNA silencing component (AGO4) in methylating target loci. We found that KYP targets are also CMT3 targets, suggesting that histone methylation maintains CNG methylation genome-wide. CMT3 and KYP targets show similar proximal distributions that correspond to the overall distribution of transposable elements of all types, whereas DRM targets are distributed more distally along the chromosome. We find an inverse relationship between element size and loss of methylation in ago4 and drm mutants. Conclusion: We conclude that the targets of both DNA methylation and histone H3K9 methylation pathways are transposable elements genome-wide, irrespective of element type and position. Our findings also suggest that RNA-directed DNA methylation is required to silence isolated elements that may be too small to be maintained in a silent state by a chromatin-based mechanism alone. Thus, parallel pathways would be needed to maintain silencing of transposable elements.}, author = {Tran, Robert K. and Zilberman, Daniel and de Bustos, Cecilia and Ditt, Renata F. and Henikoff, Jorja G. and Lindroth, Anders M. and Delrow, Jeffrey and Boyle, Tom and Kwong, Samson and Bryson, Terri D. and Jacobsen, Steven E. and Henikoff, Steven}, issn = {1465-6906}, journal = {Genome Biology}, number = {11}, publisher = {Springer Nature}, title = {{Chromatin and siRNA pathways cooperate to maintain DNA methylation of small transposable elements in Arabidopsis}}, doi = {10.1186/gb-2005-6-11-r90}, volume = {6}, year = {2005}, } @article{9529, abstract = {Eukaryotic organisms have the remarkable ability to inherit states of gene activity without altering the underlying DNA sequence. This epigenetic inheritance can persist over thousands of years, providing an alternative to genetic mutations as a substrate for natural selection. Epigenetic inheritance might be propagated by differences in DNA methylation, post-translational histone modifications, and deposition of histone variants. Mounting evidence also indicates that small interfering RNA (siRNA)-mediated mechanisms play central roles in setting up and maintaining states of gene activity. Much of the epigenetic machinery of many organisms, including Arabidopsis, appears to be directed at silencing viruses and transposable elements, with epigenetic regulation of endogenous genes being mostly derived from such processes.}, author = {Zilberman, Daniel and Henikoff, Steven}, issn = {0959-437X}, journal = {Current Opinion in Genetics and Development}, number = {5}, pages = {557--562}, publisher = {Elsevier}, title = {{Epigenetic inheritance in Arabidopsis: Selective silence}}, doi = {10.1016/j.gde.2005.07.002}, volume = {15}, year = {2005}, } @article{12203, abstract = {Geranylgeranyl diphosphate synthase (GGPPS, EC: 2.5.1.29) catalyzes the biosynthesis of geranylgeranyl diphosphate (GGPP), which is a key precursor for ginkgolide biosynthesis. Here we reported for the first time the cloning of a new full-length cDNA encoding GGPPS from the living fossil plant Ginkgo biloba. The full-length cDNA encoding G. biloba GGPPS (designated as GbGGPPS) was 1657bp long and contained a 1176bp open reading frame encoding a 391 amino acid protein. Comparative analysis showed that GbGGPPS possessed a 79 amino acid transit peptide at its N-terminal, which directed GbGGPPS to target to the plastids. Bioinformatic analysis revealed that GbGGPPS was a member of polyprenyltransferases with two highly conserved aspartate-rich motifs like other plant GGPPSs. Phylogenetic tree analysis indicated that plant GGPPSs could be classified into two groups, angiosperm and gymnosperm GGPPSs, while GbGGPPS had closer relationship with gymnosperm plant GGPPSs.}, author = {Liao, Zhihua and Chen, Min and Gong, Yifu and Guo, Liang and Tan, Qiumin and Feng, Xiaoqi and Sun, Xiaofen and Tan, Feng and Tang, Kexuan}, issn = {1042-5179}, journal = {DNA Sequence}, keywords = {Endocrinology, Genetics, Molecular Biology, Biochemistry}, number = {2}, pages = {153--158}, publisher = {Informa UK Limited}, title = {{A new geranylgeranyl Diphosphate synthase gene from Ginkgo biloba, which intermediates the biosynthesis of the key precursor for ginkgolides}}, doi = {10.1080/10425170410001667348}, volume = {15}, year = {2004}, } @article{9454, author = {Chan, Simon W.-L. and Zilberman, Daniel and Xie, Zhixin and Johansen, Lisa K. and Carrington, James C. and Jacobsen, Steven E.}, issn = {1095-9203}, journal = {Science}, keywords = {Multidisciplinary}, number = {5662}, pages = {1336}, publisher = {American Association for the Advancement of Science}, title = {{RNA silencing genes control de novo DNA methylation}}, doi = {10.1126/science.1095989}, volume = {303}, year = {2004}, } @article{9493, abstract = {In a number of organisms, transgenes containing transcribed inverted repeats (IRs) that produce hairpin RNA can trigger RNA-mediated silencing, which is associated with 21-24 nucleotide small interfering RNAs (siRNAs). In plants, IR-driven RNA silencing also causes extensive cytosine methylation of homologous DNA in both the transgene "trigger" and any other homologous DNA sequences--"targets". Endogenous genomic sequences, including transposable elements and repeated elements, are also subject to RNA-mediated silencing. The RNA silencing gene ARGONAUTE4 (AGO4) is required for maintenance of DNA methylation at several endogenous loci and for the establishment of methylation at the FWA gene. Here, we show that mutation of AGO4 substantially reduces the maintenance of DNA methylation triggered by IR transgenes, but AGO4 loss-of-function does not block the initiation of DNA methylation by IRs. AGO4 primarily affects non-CG methylation of the target sequences, while the IR trigger sequences lose methylation in all sequence contexts. Finally, we find that AGO4 and the DRM methyltransferase genes are required for maintenance of siRNAs at a subset of endogenous sequences, but AGO4 is not required for the accumulation of IR-induced siRNAs or a number of endogenous siRNAs, suggesting that AGO4 may function downstream of siRNA production.}, author = {Zilberman, Daniel and Cao, Xiaofeng and Johansen, Lisa K. and Xie, Zhixin and Carrington, James C. and Jacobsen, Steven E.}, issn = {1879-0445}, journal = {Current Biology}, number = {13}, pages = {1214--1220}, publisher = {Elsevier}, title = {{Role of Arabidopsis ARGONAUTE4 in RNA-directed DNA methylation triggered by inverted repeats}}, doi = {10.1016/j.cub.2004.06.055}, volume = {14}, year = {2004}, }