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Murray, Andrew

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Murray, Andrew
Author's Publications: search.filters.isAuthorOfPublication.d456e60e-9541-4541-9129-581304b70de2

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Now showing 1 - 10 of 26
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    Genetic drift and selection in many-allele range expansions
    (Public Library of Science, 2017) Weinstein, Bryan T.; Lavrentovich, Maxim O.; Möbius, Wolfram; Murray, Andrew; Nelson, David
    We experimentally and numerically investigate the evolutionary dynamics of four competing strains of E. coli with differing expansion velocities in radially expanding colonies. We compare experimental measurements of the average fraction, correlation functions between strains, and the relative rates of genetic domain wall annihilations and coalescences to simulations modeling the population as a one-dimensional ring of annihilating and coalescing random walkers with deterministic biases due to selection. The simulations reveal that the evolutionary dynamics can be collapsed onto master curves governed by three essential parameters: (1) an expansion length beyond which selection dominates over genetic drift; (2) a characteristic angular correlation describing the size of genetic domains; and (3) a dimensionless constant quantifying the interplay between a colony’s curvature at the frontier and its selection length scale. We measure these parameters with a new technique that precisely measures small selective differences between spatially competing strains and show that our simulations accurately predict the dynamics without additional fitting. Our results suggest that the random walk model can act as a useful predictive tool for describing the evolutionary dynamics of range expansions composed of an arbitrary number of genotypes with different fitnesses.
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    Rapid hierarchical assembly of medium-size DNA cassettes
    (Oxford University Press (OUP), 2012) Schmid-Burgk, Jonathan Leo; Xie, Zhen; Frank, Stefan; Winter, Sebastian Virreira; Mitschka, Sibylle; Kolanus, Waldemar; Murray, Andrew; Benenson, Yaakov
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    Genetically Engineered Transvestites Reveal Novel Mating Genes in Budding Yeast
    (The Genetics Society of America, 2013) Huberman, Lori Bromer; Murray, Andrew
    Haploid budding yeast has two mating types, defined by the alleles of the MAT locus, MATa and MATα. Two haploid cells of opposite mating types mate by signaling to each other using reciprocal pheromones and receptors, polarizing and growing towards each other, and eventually fusing to form a single diploid cell. The pheromones and receptors are necessary and sufficient to define a mating type, but other mating type-specific proteins make mating more efficient. We examined the role of these proteins by genetically engineering "transvestite" cells that swap the pheromone, pheromone receptor, and pheromone processing factors of one mating type for another. These cells mate with each other, but their mating is inefficient. By characterizing their mating defects and examining their transcriptomes, we found Afb1 (a-factor barrier), a novel MATα-specific protein that interferes with a-factor, the pheromone secreted by MATa cells. Strong pheromone secretion is essential for efficient mating, and the weak mating of transvestites can be improved by boosting their pheromone production. Synthetic biology can characterize the factors that control efficiency in biological processes. In yeast, selection for increased mating efficiency is likely to have continually boosted pheromone levels and the ability to discriminate between partners who make more and less pheromone. This discrimination comes at a cost: weak mating in situations where all potential partners make less pheromone.
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    Evolving a 24-hr oscillator in budding yeast
    (eLife Sciences Publications, Ltd, 2014) Wildenberg, Gregg A; Murray, Andrew
    We asked how a new, complex trait evolves by selecting for diurnal oscillations in the budding yeast, Saccharomyces cerevisiae. We expressed yellow fluorescent protein (YFP) from a yeast promoter and selected for a regular alternation between low and high fluorescence over a 24-hr period. This selection produced changes in cell adhesion rather than YFP expression: clonal populations oscillated between single cells and multicellular clumps. The oscillations are not a response to environmental cues and continue for at least three cycles in a constant environment. We identified eight putative causative mutations in one clone and recreated the evolved phenotype in the ancestral strain. The mutated genes lack obvious relationships to each other, but multiple lineages change from the haploid to the diploid pattern of gene expression. We show that a novel, complex phenotype can evolve by small sets of mutations in genes whose molecular functions appear to be unrelated to each other. DOI: http://dx.doi.org/10.7554/eLife.04875.001
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    Conservation Weighting Functions Enable Covariance Analyses to Detect Functionally Important Amino Acids
    (Public Library of Science, 2014) Colwell, Lucy J.; Brenner, Michael; Murray, Andrew
    The explosive growth in the number of protein sequences gives rise to the possibility of using the natural variation in sequences of homologous proteins to find residues that control different protein phenotypes. Because in many cases different phenotypes are each controlled by a group of residues, the mutations that separate one version of a phenotype from another will be correlated. Here we incorporate biological knowledge about protein phenotypes and their variability in the sequence alignment of interest into algorithms that detect correlated mutations, improving their ability to detect the residues that control those phenotypes. We demonstrate the power of this approach using simulations and recent experimental data. Applying these principles to the protein families encoded by Dscam and Protocadherin allows us to make testable predictions about the residues that dictate the specificity of molecular interactions.
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    Tethering Sister Centromeres to Each Other Suggests the Spindle Checkpoint Detects Stretch within the Kinetochore
    (Public Library of Science, 2014) Nannas, Natalie J.; Murray, Andrew
    The spindle checkpoint ensures that newly born cells receive one copy of each chromosome by preventing chromosomes from segregating until they are all correctly attached to the spindle. The checkpoint monitors tension to distinguish between correctly aligned chromosomes and those with both sisters attached to the same spindle pole. Tension arises when sister kinetochores attach to and are pulled toward opposite poles, stretching the chromatin around centromeres and elongating kinetochores. We distinguished between two hypotheses for where the checkpoint monitors tension: between the kinetochores, by detecting alterations in the distance between them, or by responding to changes in the structure of the kinetochore itself. To distinguish these models, we inhibited chromatin stretch by tethering sister chromatids together by binding a tetrameric form of the Lac repressor to arrays of the Lac operator located on either side of a centromere. Inhibiting chromatin stretch did not activate the spindle checkpoint; these cells entered anaphase at the same time as control cells that express a dimeric version of the Lac repressor, which cannot cross link chromatids, and cells whose checkpoint has been inactivated. There is no dominant checkpoint inhibition when sister kinetochores are held together: cells expressing the tetrameric Lac repressor still arrest in response to microtubule-depolymerizing drugs. Tethering chromatids together does not disrupt kinetochore function; chromosomes are successfully segregated to opposite poles of the spindle. Our results indicate that the spindle checkpoint does not monitor inter-kinetochore separation, thus supporting the hypothesis that tension is measured within the kinetochore.
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    Sucrose Utilization in Budding Yeast as a Model for the Origin of Undifferentiated Multicellularity
    (Public Library of Science (PLoS), 2011) Koschwanez, John H; Foster, Kevin R.; Murray, Andrew
    We use the budding yeast, Saccharomyces cerevisiae, to investigate one model for the initial emergence of multicellularity: the formation of multicellular aggregates as a result of incomplete cell separation. We combine simulations with experiments to show how the use of secreted public goods favors the formation of multicellular aggregates. Yeast cells can cooperate by secreting invertase, an enzyme that digests sucrose into monosaccharides, and many wild isolates are multicellular because cell walls remain attached to each other after the cells divide. We manipulate invertase secretion and cell attachment, and show that multicellular clumps have two advantages over single cells: they grow under conditions where single cells cannot and they compete better against cheaters, cells that do not make invertase. We propose that the prior use of public goods led to selection for the incomplete cell separation that first produced multicellularity.
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    Asymmetry in Sexual Pheromones Is Not Required for Ascomycete Mating
    (Elsevier BV, 2011) Gonçalves-Sá, Joana; Murray, Andrew
    Highlights Asymmetric modification of pheromones is not required for yeast mating Two yeast strains that express complementary pheromones and receptors mate with each other Two yeast strains that express the same mating-type allele can mate with each other Receptors and the pheromones determine the sexual identity of budding yeast Summary Background We investigated the determinants of sexual identity in the budding yeast Saccharomyces cerevisiae. The higher fungi are divided into the ascomycetes and the basidiomycetes. Most ascomycetes have two mating types: one (called α in yeasts and MAT1-1 in filamentous fungi) produces a small, unmodified, peptide pheromone, and the other (a in yeasts and MAT1-2 in filamentous fungi) produces a peptide pheromone conjugated to a C-terminal farnesyl group that makes it very hydrophobic. In the basidiomycetes, all pheromones are lipid-modified, and this difference is a distinguishing feature between the phyla. We asked whether the asymmetry in pheromone modification is required for successful mating in ascomycetes. Results We cloned receptor and pheromone genes from a filamentous ascomycete and a basidiomycete and expressed these in the budding yeast, Saccharomyces cerevisiae, to generate novel, alternative mating pairs. We find that two yeast cells can mate even when both cells secrete a-like or α-like peptides. Importantly, this is true regardless of whether the cells express the a- or α-mating-type loci, which control the expression of other, sex-specific genes, in addition to the pheromones and pheromone receptors. Conclusions We demonstrate that the asymmetric pheromone modification is not required for successful mating of ascomycete fungi and confirm that, in budding yeast, the primary determinants of mating are the specificity of the receptors and their corresponding pheromones.
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    Complications Dawn for Kinetochore Regulation by Aurora
    (Proceedings of the National Academy of Sciences, 2012) Nannas, Natalie Jo; Murray, Andrew
    Organisms must faithfully segregate their chromosomes during cell division; mistakes in this process can be costly and even fatal to the organism (1, 2). During mitosis, replicated chromosomes attach to the spindle, a dynamic system of microtubules organized around two poles. Chromosomes attach to the spindle via kinetochores, structures that form on centromeres and bind the ends of microtubules. For accurate segregation, kinetochores on sister chromosomes must attach to microtubules from opposite poles; incorrect attachments lead to missegregation (3). In PNAS, Umbreit et al. (4) expand our understanding of how kinetochore–microtubule interactions can be regulated to correct improper attachments. The authors use in vitro studies to demonstrate that a component of the kinetochore, the Ndc80 complex, can directly influence the dynamics of the microtubules it is bound to and how the complex can be regulated to correct errors in chromosome attachment. Kinetochores are complicated machines. They can stay attached to microtubule ends as they grow and shrink, regulate the dynamics of microtubules, regulate their own activity, and signal to the remainder of the cell. The outer layer of the kinetochore contains the dumbbell-shaped Ndc80 complex (5): One globular domain [the N-terminal domains of Hec1 (Ndc80 in budding yeast) and Nuf2] binds microtubules (6) and is connected by a long coiled coil to the other globular domain (composed of the C-terminal domains of Spc24/Spc25), which connects to other kinetochore components (7) (Fig. 1A). Hec1 contains a conserved calponin homology domain and an unstructured N-terminal tail: Both regions can bind to microtubules independently, but they must act together to produce high-affinity binding (5⇓⇓–8). When sister kinetochores attach...(see full text).
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    A Predictive Model for Yeast Cell Polarization in Pheromone Gradients
    (Public Library of Science, 2016) Muller, Nicolas; Piel, Matthieu; Calvez, Vincent; Voituriez, Raphaël; Gonçalves-Sá, Joana; Guo, Chin-Lin; Jiang, Xingyu; Murray, Andrew; Meunier, Nicolas
    Budding yeast cells exist in two mating types, a and α, which use peptide pheromones to communicate with each other during mating. Mating depends on the ability of cells to polarize up pheromone gradients, but cells also respond to spatially uniform fields of pheromone by polarizing along a single axis. We used quantitative measurements of the response of a cells to α-factor to produce a predictive model of yeast polarization towards a pheromone gradient. We found that cells make a sharp transition between budding cycles and mating induced polarization and that they detect pheromone gradients accurately only over a narrow range of pheromone concentrations corresponding to this transition. We fit all the parameters of the mathematical model by using quantitative data on spontaneous polarization in uniform pheromone concentration. Once these parameters have been computed, and without any further fit, our model quantitatively predicts the yeast cell response to pheromone gradient providing an important step toward understanding how cells communicate with each other.