@article{8454, abstract = {Magic-angle spinning solid-state NMR spectroscopy is an important technique to study molecular structure, dynamics and interactions, and is rapidly gaining importance in biomolecular sciences. Here we provide an overview of experimental approaches to study molecular dynamics by MAS solid-state NMR, with an emphasis on the underlying theoretical concepts and differences of MAS solid-state NMR compared to solution-state NMR. The theoretical foundations of nuclear spin relaxation are revisited, focusing on the particularities of spin relaxation in solid samples under magic-angle spinning. We discuss the range of validity of Redfield theory, as well as the inherent multi-exponential behavior of relaxation in solids. Experimental challenges for measuring relaxation parameters in MAS solid-state NMR and a few recently proposed relaxation approaches are discussed, which provide information about time scales and amplitudes of motions ranging from picoseconds to milliseconds. We also discuss the theoretical basis and experimental measurements of anisotropic interactions (chemical-shift anisotropies, dipolar and quadrupolar couplings), which give direct information about the amplitude of motions. The potential of combining relaxation data with such measurements of dynamically-averaged anisotropic interactions is discussed. Although the focus of this review is on the theoretical foundations of dynamics studies rather than their application, we close by discussing a small number of recent dynamics studies, where the dynamic properties of proteins in crystals are compared to those in solution.}, author = {Schanda, Paul and Ernst, Matthias}, issn = {0079-6565}, journal = {Progress in Nuclear Magnetic Resonance Spectroscopy}, number = {8}, pages = {1--46}, publisher = {Elsevier}, title = {{Studying dynamics by magic-angle spinning solid-state NMR spectroscopy: Principles and applications to biomolecules}}, doi = {10.1016/j.pnmrs.2016.02.001}, volume = {96}, year = {2016}, } @article{8455, abstract = {Solid-state NMR spectroscopy allows the characterization of the structure, interactions and dynamics of insoluble and/or very large proteins. Sensitivity and resolution are often major challenges for obtaining atomic-resolution information, in particular for very large protein complexes. Here we show that the use of deuterated, specifically CH3-labelled proteins result in significant sensitivity gains compared to previously employed CHD2 labelling, while line widths increase only marginally. We apply this labelling strategy to a 468 kDa-large dodecameric aminopeptidase, TET2, and the 1.6 MDa-large 50S ribosome subunit of Thermus thermophilus.}, author = {Kurauskas, Vilius and Crublet, Elodie and Macek, Pavel and Kerfah, Rime and Gauto, Diego F. and Boisbouvier, Jérôme and Schanda, Paul}, issn = {1359-7345}, journal = {Chemical Communications}, keywords = {Materials Chemistry, Electronic, Optical and Magnetic Materials, General Chemistry, Surfaces, Coatings and Films, Metals and Alloys, Ceramics and Composites, Catalysis}, number = {61}, pages = {9558--9561}, publisher = {Royal Society of Chemistry}, title = {{Sensitive proton-detected solid-state NMR spectroscopy of large proteins with selective CH3labelling: Application to the 50S ribosome subunit}}, doi = {10.1039/c6cc04484k}, volume = {52}, year = {2016}, } @article{849, abstract = {Understanding the principles that led to the current complexity of the genetic code is a central question in evolution. Expansion of the genetic code required the selection of new transfer RNAs (tRNAs) with specific recognition signals that allowed them to be matured, modified, aminoacylated, and processed by the ribosome without compromising the fidelity or efficiency of protein synthesis. We show that saturation of recognition signals blocks the emergence of new tRNA identities and that the rate of nucleotide substitutions in tRNAs is higher in species with fewer tRNA genes. We propose that the growth of the genetic code stalled because a limit was reached in the number of identity elements that can be effectively used in the tRNA structure.}, author = {Saint Léger, Adélaïde and Bello, Carla and Dans, Pablo and Torres, Adrian and Novoa, Eva and Camacho, Noelia and Orozco, Modesto and Kondrashov, Fyodor and Ribas De Pouplana, Lluís}, issn = {2375-2548}, journal = {Science advances}, number = {4}, publisher = {American Association for the Advancement of Science}, title = {{Saturation of recognition elements blocks evolution of new tRNA identities}}, doi = {10.1126/sciadv.1501860}, volume = {2}, year = {2016}, } @article{8493, abstract = {In this paper we study a so-called separatrix map introduced by Zaslavskii–Filonenko (Sov Phys JETP 27:851–857, 1968) and studied by Treschev (Physica D 116(1–2):21–43, 1998; J Nonlinear Sci 12(1):27–58, 2002), Piftankin (Nonlinearity (19):2617–2644, 2006) Piftankin and Treshchëv (Uspekhi Mat Nauk 62(2(374)):3–108, 2007). We derive a second order expansion of this map for trigonometric perturbations. In Castejon et al. (Random iteration of maps of a cylinder and diffusive behavior. Preprint available at arXiv:1501.03319, 2015), Guardia and Kaloshin (Stochastic diffusive behavior through big gaps in a priori unstable systems (in preparation), 2015), and Kaloshin et al. (Normally Hyperbolic Invariant Laminations and diffusive behavior for the generalized Arnold example away from resonances. Preprint available at http://www.terpconnect.umd.edu/vkaloshi/, 2015), applying the results of the present paper, we describe a class of nearly integrable deterministic systems with stochastic diffusive behavior.}, author = {Guardia, M. and Kaloshin, Vadim and Zhang, J.}, issn = {0010-3616}, journal = {Communications in Mathematical Physics}, pages = {321--361}, publisher = {Springer Nature}, title = {{A second order expansion of the separatrix map for trigonometric perturbations of a priori unstable systems}}, doi = {10.1007/s00220-016-2705-9}, volume = {348}, year = {2016}, } @article{8494, abstract = {We prove a form of Arnold diffusion in the a-priori stable case. Let H0(p)+ϵH1(θ,p,t),θ∈Tn,p∈Bn,t∈T=R/T, be a nearly integrable system of arbitrary degrees of freedom n⩾2 with a strictly convex H0. We show that for a “generic” ϵH1, there exists an orbit (θ,p) satisfying ∥p(t)−p(0)∥>l(H1)>0, where l(H1) is independent of ϵ. The diffusion orbit travels along a codimension-1 resonance, and the only obstruction to our construction is a finite set of additional resonances. For the proof we use a combination of geometric and variational methods, and manage to adapt tools which have recently been developed in the a-priori unstable case.}, author = {Bernard, Patrick and Kaloshin, Vadim and Zhang, Ke}, issn = {0001-5962}, journal = {Acta Mathematica}, number = {1}, pages = {1--79}, publisher = {Institut Mittag-Leffler}, title = {{Arnold diffusion in arbitrary degrees of freedom and normally hyperbolic invariant cylinders}}, doi = {10.1007/s11511-016-0141-5}, volume = {217}, year = {2016}, } @article{8496, author = {Avila, Artur and De Simoi, Jacopo and Kaloshin, Vadim}, issn = {0003-486X}, journal = {Annals of Mathematics}, number = {2}, pages = {527--558}, publisher = {Princeton University Press}, title = {{An integrable deformation of an ellipse of small eccentricity is an ellipse}}, doi = {10.4007/annals.2016.184.2.5}, volume = {184}, year = {2016}, } @article{8497, abstract = {We study the dynamics of the restricted planar three-body problem near mean motion resonances, i.e. a resonance involving the Keplerian periods of the two lighter bodies revolving around the most massive one. This problem is often used to model Sun–Jupiter–asteroid systems. For the primaries (Sun and Jupiter), we pick a realistic mass ratio μ=10−3 and a small eccentricity e0>0. The main result is a construction of a variety of non local diffusing orbits which show a drastic change of the osculating (instant) eccentricity of the asteroid, while the osculating semi major axis is kept almost constant. The proof relies on the careful analysis of the circular problem, which has a hyperbolic structure, but for which diffusion is prevented by KAM tori. In the proof we verify certain non-degeneracy conditions numerically. Based on the work of Treschev, it is natural to conjecture that the time of diffusion for this problem is ∼−ln(μe0)μ3/2e0. We expect our instability mechanism to apply to realistic values of e0 and we give heuristic arguments in its favor. If so, the applicability of Nekhoroshev theory to the three-body problem as well as the long time stability become questionable. It is well known that, in the Asteroid Belt, located between the orbits of Mars and Jupiter, the distribution of asteroids has the so-called Kirkwood gaps exactly at mean motion resonances of low order. Our mechanism gives a possible explanation of their existence. To relate the existence of Kirkwood gaps with Arnol'd diffusion, we also state a conjecture on its existence for a typical ϵ-perturbation of the product of the pendulum and the rotator. Namely, we predict that a positive conditional measure of initial conditions concentrated in the main resonance exhibits Arnol’d diffusion on time scales −lnϵϵ2.}, author = {Féjoz, Jacques and Guàrdia, Marcel and Kaloshin, Vadim and Roldán, Pablo}, issn = {1435-9855}, journal = {Journal of the European Mathematical Society}, number = {10}, pages = {2315--2403}, publisher = {European Mathematical Society Publishing House}, title = {{Kirkwood gaps and diffusion along mean motion resonances in the restricted planar three-body problem}}, doi = {10.4171/jems/642}, volume = {18}, year = {2016}, } @article{850, abstract = {Fitness landscapes depict how genotypes manifest at the phenotypic level and form the basis of our understanding of many areas of biology, yet their properties remain elusive. Previous studies have analysed specific genes, often using their function as a proxy for fitness, experimentally assessing the effect on function of single mutations and their combinations in a specific sequence or in different sequences. However, systematic high-throughput studies of the local fitness landscape of an entire protein have not yet been reported. Here we visualize an extensive region of the local fitness landscape of the green fluorescent protein from Aequorea Victoria (avGFP) by measuring the native function (fluorescence) of tens of thousands of derivative genotypes of avGFP. We show that the fitness landscape of avGFP is narrow, with 3/4 of the derivatives with a single mutation showing reduced fluorescence and half of the derivatives with four mutations being completely non-fluorescent. The narrowness is enhanced by epistasis, which was detected in up to 30% of genotypes with multiple mutations and mostly occurred through the cumulative effect of slightly deleterious mutations causing a threshold-like decrease in protein stability and a concomitant loss of fluorescence. A model of orthologous sequence divergence spanning hundreds of millions of years predicted the extent of epistasis in our data, indicating congruence between the fitness landscape properties at the local and global scales. The characterization of the local fitness landscape of avGFP has important implications for several fields including molecular evolution, population genetics and protein design.}, author = {Sarkisyan, Karen and Bolotin, Dmitry and Meer, Margarita and Usmanova, Dinara and Mishin, Alexander and Sharonov, George and Ivankov, Dmitry and Bozhanova, Nina and Baranov, Mikhail and Soylemez, Onuralp and Bogatyreva, Natalya and Vlasov, Peter and Egorov, Evgeny and Logacheva, Maria and Kondrashov, Alexey and Chudakov, Dmitriy and Putintseva, Ekaterina and Mamedov, Ilgar and Tawfik, Dan and Lukyanov, Konstantin and Kondrashov, Fyodor}, issn = {1476-4687}, journal = {Nature}, pages = {397 -- 401}, publisher = {Springer Nature}, title = {{Local fitness landscape of the green fluorescent protein}}, doi = {10.1038/nature17995}, volume = {533}, year = {2016}, } @article{853, abstract = {A comparative analysis of the metagenomes from two 30 000-year-old permafrost samples, one of lake-alluvial origin and the other from late Pleistocene Ice Complex sediments, revealed significant differences within microbial communities. The late Pleistocene Ice Complex sediments (which have been characterized by the absence of methane with lower values of redox potential and Fe2+ content) showed a low abundance of methanogenic archaea and enzymes from both the carbon and nitrogen cycles, but a higher abundance of enzymes associated with the sulfur cycle. The metagenomic and geochemical analyses described in the paper provide evidence that the formation of the sampled late Pleistocene Ice Complex sediments likely took place under much more aerobic conditions than lake-alluvial sediments.}, author = {Rivkina, Elizaveta and Petrovskaya, Lada and Vishnivetskaya, Tatiana and Krivushin, Kirill and Shmakova, Lyubov and Tutukina, Maria and Meyers, Arthur and Kondrashov, Fyodor}, issn = {1726-4189}, journal = {Biogeosciences}, number = {7}, pages = {2207 -- 2219}, publisher = {European Geosciences Union}, title = {{Metagenomic analyses of the late Pleistocene permafrost - Additional tools for reconstruction of environmental conditions}}, doi = {10.5194/bg-13-2207-2016}, volume = {13}, year = {2016}, } @article{896, abstract = {Multicellular eukaryotes have evolved a range of mechanisms for immune recognition. A widespread family involved in innate immunity are the NACHT-domain and leucine-rich-repeat-containing (NLR) proteins.Mammals have small numbers of NLR proteins, whereas in some species, mostly those without adaptive immune systems, NLRs have expanded into very large families.We describe a family of nearly 400NLR proteins encoded in the zebrafish genome. The proteins share a defining overall structure, which arose in fishes after a fusion of the core NLR domains with a B30.2 domain, but can be subdivided into four groups based on their NACHT domains. Gene conversion acting differentially on the NACHT and B30.2 domains has shaped the family and created the groups. Evidence of positive selection in the B30.2 domain indicates that this domain rather than the leucine-rich repeats acts as the pathogen recognition module. In an unusual chromosomal organization, the majority of the genes are located on one chromosome arm, interspersed with other large multigene families, including a new family encoding zinc-finger proteins. The NLR-B30.2 proteins represent a new family with diversity in the specific recognition module that is present in fishes in spite of the parallel existence of an adaptive immune system.}, author = {Howe, Kerstin and Schiffer, Philipp and Zielinski, Julia and Wiehe, Thomas and Laird, Gavin and Marioni, John and Soylemez, Onuralp and Kondrashov, Fyodor and Leptin, Maria}, issn = {2046-2441}, journal = {Open Biology}, keywords = {NACHT, B30, SPRY, Gene conversion, Innate immune system, Genome evolution}, number = {4}, publisher = {Royal Society, The}, title = {{Structure and evolutionary history of a large family of NLR proteins in the zebrafish}}, doi = {10.1098/rsob.160009}, volume = {6}, year = {2016}, } @article{9019, abstract = {Targeting protein–protein interactions has long been considered as a very difficult if impossible task, but over the past decade, front lines have moved. The number of successful examples is exponentially growing. This review presents a rapid overview of recent advances in this field considering the strengths and weaknesses of the small molecule approaches and alternative strategies such as the selection or design of artificial antibodies, peptides or peptidomimetics.}, author = {Bakail, May M and Ochsenbein, Francoise}, issn = {1631-0748}, journal = {Comptes Rendus Chimie}, keywords = {General Chemistry, General Chemical Engineering}, number = {1-2}, pages = {19--27}, publisher = {Elsevier}, title = {{Targeting protein–protein interactions, a wide open field for drug design}}, doi = {10.1016/j.crci.2015.12.004}, volume = {19}, year = {2016}, } @article{9051, abstract = {Biological systems often involve the self-assembly of basic components into complex and functioning structures. Artificial systems that mimic such processes can provide a well-controlled setting to explore the principles involved and also synthesize useful micromachines. Our experiments show that immotile, but active, components self-assemble into two types of structure that exhibit the fundamental forms of motility: translation and rotation. Specifically, micron-scale metallic rods are designed to induce extensile surface flows in the presence of a chemical fuel; these rods interact with each other and pair up to form either a swimmer or a rotor. Such pairs can transition reversibly between these two configurations, leading to kinetics reminiscent of bacterial run-and-tumble motion.}, author = {Davies Wykes, Megan S. and Palacci, Jérémie A and Adachi, Takuji and Ristroph, Leif and Zhong, Xiao and Ward, Michael D. and Zhang, Jun and Shelley, Michael J.}, issn = {1744-6848}, journal = {Soft Matter}, number = {20}, pages = {4584--4589}, publisher = {Royal Society of Chemistry}, title = {{Dynamic self-assembly of microscale rotors and swimmers}}, doi = {10.1039/c5sm03127c}, volume = {12}, year = {2016}, } @article{9052, abstract = {We describe colloidal Janus particles with metallic and dielectric faces that swim vigorously when illuminated by defocused optical tweezers without consuming any chemical fuel. Rather than wandering randomly, these optically-activated colloidal swimmers circulate back and forth through the beam of light, tracing out sinuous rosette patterns. We propose a model for this mode of light-activated transport that accounts for the observed behavior through a combination of self-thermophoresis and optically-induced torque. In the deterministic limit, this model yields trajectories that resemble rosette curves known as hypotrochoids.}, author = {Moyses, Henrique and Palacci, Jérémie A and Sacanna, Stefano and Grier, David G.}, issn = {1744-6848}, journal = {Soft Matter}, keywords = {General Chemistry, Condensed Matter Physics}, number = {30}, pages = {6357--6364}, publisher = {Royal Society of Chemistry }, title = {{Trochoidal trajectories of self-propelled Janus particles in a diverging laser beam}}, doi = {10.1039/c6sm01163b}, volume = {12}, year = {2016}, } @article{9140, abstract = {Expected changes to future extreme precipitation remain a key uncertainty associated with anthropogenic climate change. Extreme precipitation has been proposed to scale with the precipitable water content in the atmosphere. Assuming constant relative humidity, this implies an increase of precipitation extremes at a rate of about 7% °C−1 globally as indicated by the Clausius‐Clapeyron relationship. Increases faster and slower than Clausius‐Clapeyron have also been reported. In this work, we examine the scaling between precipitation extremes and temperature in the present climate using simulations and measurements from surface weather stations collected in the frame of the HyMeX and MED‐CORDEX programs in Southern France. Of particular interest are departures from the Clausius‐Clapeyron thermodynamic expectation, their spatial and temporal distribution, and their origin. Looking at the scaling of precipitation extreme with temperature, two regimes emerge which form a hook shape: one at low temperatures (cooler than around 15°C) with rates of increase close to the Clausius‐Clapeyron rate and one at high temperatures (warmer than about 15°C) with sub‐Clausius‐Clapeyron rates and most often negative rates. On average, the region of focus does not seem to exhibit super Clausius‐Clapeyron behavior except at some stations, in contrast to earlier studies. Many factors can contribute to departure from Clausius‐Clapeyron scaling: time and spatial averaging, choice of scaling temperature (surface versus condensation level), and precipitation efficiency and vertical velocity in updrafts that are not necessarily constant with temperature. But most importantly, the dynamical contribution of orography to precipitation in the fall over this area during the so‐called “Cevenoles” events, explains the hook shape of the scaling of precipitation extremes.}, author = {Drobinski, P. and Alonzo, B. and Bastin, S. and Silva, N. Da and Muller, Caroline J}, issn = {2169-897X}, journal = {Journal of Geophysical Research: Atmospheres}, number = {7}, pages = {3100--3119}, publisher = {American Geophysical Union}, title = {{Scaling of precipitation extremes with temperature in the French Mediterranean region: What explains the hook shape?}}, doi = {10.1002/2015jd023497}, volume = {121}, year = {2016}, } @article{92, abstract = {Advanced organic nonlinear optical (NLO) materials have attracted increasing attention due to their multitude of applications in modern telecommunication devices. Arguably the most important advantage of organic NLO materials, relative to traditionally used inorganic NLO materials, is their short optical response time. Geminal amido esters with their donor-π-acceptor (D-π-A) architecture exhibit high levels of electron delocalization and substantial intramolecular charge transfer, which should endow these materials with short optical response times and large molecular (hyper)polarizabilities. In order to test this hypothesis, the linear and second-order nonlinear optical properties of five geminal amido esters, (E)-ethyl 3-(X-phenylamino)-2-(Y-phenylcarbamoyl)acrylate (1, X = 4-H, Y = 4-H; 2, X = 4-CH3, Y = 4-CH3; 3, X = 4-NO2, Y = 2,5-OCH3; 4, X = 2-Cl, Y = 2-Cl; 5, X = 4-Cl, Y = 4-Cl) were synthesized and characterized, whereby NLO structure-function relationships were established including intramolecular charge transfer characteristics, crystal field effects, and molecular first hyperpolarizabilities (β). Given the typically large errors (10-30%) associated with the determination of β coefficients, three independent methods were used: (i) density functional theory, (ii) hyper-Rayleigh scattering, and (iii) high-resolution X-ray diffraction data analysis based on multipolar modeling of electron densities at each atom. These three methods delivered consistent values of β, and based on these results, 3 should hold the most promise for NLO applications. The correlation between the molecular structure of these geminal amido esters and their linear and nonlinear optical properties thus provide molecular design guidelines for organic NLO materials; this leads to the ultimate goal of generating bespoke organic molecules to suit a given NLO device application.}, author = {Cole, Jaqueline and Lin, Tzechia and Ashcroft, Christopher and Pérez Moreno, Javier and Tan, Yizhou and Venkatesan, Perumal and Higginbotham, Andrew P and Pattison, Philip and Edwards, Alison and Piltz, Ross and Clays, Koen and Ilangovan, Andivelu}, journal = {Journal of Physical Chemistry C}, number = {51}, pages = {29439 -- 29448}, publisher = {American Chemical Society}, title = {{Relating the structure of geminal Amido Esters to their molecular hyperpolarizability}}, doi = {10.1021/acs.jpcc.6b10724}, volume = {120}, year = {2016}, } @article{930, abstract = {The changes in cell dynamics after oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the effect of oncogenic hedgehog signalling in distinct cell populations and their capacity to induce basal cell carcinoma, the most frequent cancer in humans. We found that only stem cells, and not progenitors, initiated tumour formation upon oncogenic hedgehog signalling. This difference was due to the hierarchical organization of tumour growth in oncogene-targeted stem cells, characterized by an increase in symmetric self-renewing divisions and a higher p53-dependent resistance to apoptosis, leading to rapid clonal expansion and progression into invasive tumours. Our work reveals that the capacity of oncogene-targeted cells to induce tumour formation is dependent not only on their long-term survival and expansion, but also on the specific clonal dynamics of the cancer cell of origin.}, author = {Sánchez Danés, Adriana and Hannezo, Edouard B and Larsimont, Jean and Liagre, Mélanie and Youssef, Khalil and Simons, Benjamin and Blanpain, Cédric}, issn = {0028-0836}, journal = {Nature}, pages = {298 -- 303}, publisher = {Springer Nature}, title = {{Defining the clonal dynamics leading to mouse skin tumour initiation}}, doi = {10.1038/nature19069}, volume = {536}, year = {2016}, } @article{931, abstract = {In many adult tissues, stem cells and differentiated cells are not homogeneously distributed: stem cells are arranged in periodic "niches," and differentiated cells are constantly produced and migrate out of these niches. In this article, we provide a general theoretical framework to study mixtures of dividing and actively migrating particles, which we apply to biological tissues. We show in particular that the interplay between the stresses arising from active cell migration and stem cell division give rise to robust stem cell patterns. The instability of the tissue leads to spatial patterns which are either steady or oscillating in time. The wavelength of the instability has an order of magnitude consistent with the biological observations. We also discuss the implications of these results for future in vitro and in vivo experiments.}, author = {Hannezo, Edouard B and Coucke, Alice and Joanny, Jean}, issn = {2470-0053}, journal = {Physical Review E }, number = {2}, publisher = {American Institute of Physics}, title = {{Interplay of migratory and division forces as a generic mechanism for stem cell patterns}}, doi = {10.1103/PhysRevE.93.022405}, volume = {93}, year = {2016}, } @article{932, abstract = {Epithelial sheets are crucial components of all metazoan animals, enclosing organs and protecting the animal from its environment. Epithelial homeostasis poses unique challenges, as addition of new cells and loss of old cells must be achieved without disrupting the fluid-tight barrier and apicobasal polarity of the epithelium. Several studies have identified cell biological mechanisms underlying extrusion of cells from epithelia, but far less is known of the converse mechanism by which new cells are added. Here, we combine molecular, pharmacological, and laser-dissection experiments with theoretical modeling to characterize forces driving emergence of an apical surface as single nascent cells are added to a vertebrate epithelium in vivo. We find that this process involves the interplay between cell-autonomous actin-generated pushing forces in the emerging cell and mechanical properties of neighboring cells. Our findings define the forces driving this cell behavior, contributing to a more comprehensive understanding of epithelial homeostasis.}, author = {Sedzinski, Jakub and Hannezo, Edouard B and Tu, Fan and Biro, Maté and Wallingford, John}, issn = {1878-1551}, journal = {Developmental Cell}, number = {1}, pages = {24 -- 35}, publisher = {Elsevier}, title = {{Emergence of an Apical Epithelial Cell Surface In Vivo}}, doi = {10.1016/j.devcel.2015.12.013}, volume = {36}, year = {2016}, } @article{9456, abstract = {The discovery of introns four decades ago was one of the most unexpected findings in molecular biology. Introns are sequences interrupting genes that must be removed as part of messenger RNA production. Genome sequencing projects have shown that most eukaryotic genes contain at least one intron, and frequently many. Comparison of these genomes reveals a history of long evolutionary periods during which few introns were gained, punctuated by episodes of rapid, extensive gain. However, although several detailed mechanisms for such episodic intron generation have been proposed, none has been empirically supported on a genomic scale. Here we show how short, non-autonomous DNA transposons independently generated hundreds to thousands of introns in the prasinophyte Micromonas pusilla and the pelagophyte Aureococcus anophagefferens. Each transposon carries one splice site. The other splice site is co-opted from the gene sequence that is duplicated upon transposon insertion, allowing perfect splicing out of the RNA. The distributions of sequences that can be co-opted are biased with respect to codons, and phasing of transposon-generated introns is similarly biased. These transposons insert between pre-existing nucleosomes, so that multiple nearby insertions generate nucleosome-sized intervening segments. Thus, transposon insertion and sequence co-option may explain the intron phase biases and prevalence of nucleosome-sized exons observed in eukaryotes. Overall, the two independent examples of proliferating elements illustrate a general DNA transposon mechanism that can plausibly account for episodes of rapid, extensive intron gain during eukaryotic evolution.}, author = {Huff, Jason T. and Zilberman, Daniel and Roy, Scott W.}, issn = {1476-4687}, journal = {Nature}, number = {7626}, pages = {533--536}, publisher = {Springer Nature }, title = {{Mechanism for DNA transposons to generate introns on genomic scales}}, doi = {10.1038/nature20110}, volume = {538}, year = {2016}, } @article{9473, abstract = {Cytosine DNA methylation regulates the expression of eukaryotic genes and transposons. Methylation is copied by methyltransferases after DNA replication, which results in faithful transmission of methylation patterns during cell division and, at least in flowering plants, across generations. Transgenerational inheritance is mediated by a small group of cells that includes gametes and their progenitors. However, methylation is usually analyzed in somatic tissues that do not contribute to the next generation, and the mechanisms of transgenerational inheritance are inferred from such studies. To gain a better understanding of how DNA methylation is inherited, we analyzed purified Arabidopsis thaliana sperm and vegetative cells-the cell types that comprise pollen-with mutations in the DRM, CMT2, and CMT3 methyltransferases. We find that DNA methylation dependency on these enzymes is similar in sperm, vegetative cells, and somatic tissues, although DRM activity extends into heterochromatin in vegetative cells, likely reflecting transcription of heterochromatic transposons in this cell type. We also show that lack of histone H1, which elevates heterochromatic DNA methylation in somatic tissues, does not have this effect in pollen. Instead, levels of CG methylation in wild-type sperm and vegetative cells, as well as in wild-type microspores from which both pollen cell types originate, are substantially higher than in wild-type somatic tissues and similar to those of H1-depleted roots. Our results demonstrate that the mechanisms of methylation maintenance are similar between pollen and somatic cells, but the efficiency of CG methylation is higher in pollen, allowing methylation patterns to be accurately inherited across generations.}, author = {Hsieh, Ping-Hung and He, Shengbo and Buttress, Toby and Gao, Hongbo and Couchman, Matthew and Fischer, Robert L. and Zilberman, Daniel and Feng, Xiaoqi}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {52}, pages = {15132--15137}, publisher = {National Academy of Sciences}, title = {{Arabidopsis male sexual lineage exhibits more robust maintenance of CG methylation than somatic tissues}}, doi = {10.1073/pnas.1619074114}, volume = {113}, year = {2016}, }