@article{12198, abstract = {The Arabidopsis thaliana central cell, the companion cell of the egg, undergoes DNA demethylation before fertilization, but the targeting preferences, mechanism, and biological significance of this process remain unclear. Here, we show that active DNA demethylation mediated by the DEMETER DNA glycosylase accounts for all of the demethylation in the central cell and preferentially targets small, AT-rich, and nucleosome-depleted euchromatic transposable elements. The vegetative cell, the companion cell of sperm, also undergoes DEMETER-dependent demethylation of similar sequences, and lack of DEMETER in vegetative cells causes reduced small RNA–directed DNA methylation of transposons in sperm. Our results demonstrate that demethylation in companion cells reinforces transposon methylation in plant gametes and likely contributes to stable silencing of transposable elements across generations.}, author = {Ibarra, Christian A. and Feng, Xiaoqi and Schoft, Vera K. and Hsieh, Tzung-Fu and Uzawa, Rie and Rodrigues, Jessica A. and Zemach, Assaf and Chumak, Nina and Machlicova, Adriana and Nishimura, Toshiro and Rojas, Denisse and Fischer, Robert L. and Tamaru, Hisashi and Zilberman, Daniel}, issn = {1095-9203}, journal = {Science}, keywords = {Multidisciplinary}, number = {6100}, pages = {1360--1364}, publisher = {American Association for the Advancement of Science}, title = {{Active DNA demethylation in plant companion cells reinforces transposon methylation in gametes}}, doi = {10.1126/science.1224839}, volume = {337}, year = {2012}, } @article{12644, abstract = {In the Dry Andes of central Chile, summer water resources originate mostly from snowmelt and ice melt. We use the physically based, spatially distributed hydrological model TOPKAPI to study the exchange between glaciers and climate in the upper Aconcagua River Basin during the summer season and identify the model parameters that are robust and transferable and those that are more dependent on calibration. TOPKAPI has recently been adapted to incorporate an enhanced temperature index approach for snow and ice melting. We suggest a calibration procedure that allows calibration of parameters in three steps by separating parameters governing distinct processes. We evaluate the parameters' transferability in time and in space by applying the model at two spatial scales. TOPKAPI's ability to simulate the relevant processes is tested against meteorological, ablation, and glacier runoff data measured on Juncal Norte Glacier during two glacier ablation seasons. The model was applied successfully to the climatic setting of the Dry Andes once its parameters were recalibrated. We found a clear distinction between parameters that are stable in time and those that need recalibration. The parameters of the melt model are transferable from one season to the other, while the parameters governing the extrapolation of meteorological input data and the routing of glacier meltwater need recalibration from one season to the other. Sensitivity analysis revealed that the model is most sensitive to the temperature lapse rate governing the extrapolation of air temperature from point measurements to the glacier scale and to the melt parameter that multiplies the shortwave radiation balance.}, author = {Ragettli, S. and Pellicciotti, Francesca}, issn = {0043-1397}, journal = {Water Resources Research}, number = {3}, publisher = {American Geophysical Union}, title = {{Calibration of a physically based, spatially distributed hydrological model in a glacierized basin: On the use of knowledge from glaciometeorological processes to constrain model parameters}}, doi = {10.1029/2011wr010559}, volume = {48}, year = {2012}, } @article{12646, abstract = {Assessment of water resources from remote mountainous catchments plays a crucial role for the development of rural areas in or in the vicinity of mountain ranges. The scarcity of data, however, prevents the application of standard approaches that are based on data-driven models. The Hindu Kush–Karakoram–Himalaya mountain range is a crucial area in terms of water resources, but our understanding of the response of its high-elevation catchments to a changing climate is hindered by lack of hydro-meteorological and cryospheric data. Hydrological modeling is challenging here because internal inconsistencies—such as an underestimation of precipitation input that can be compensated for by an overestimation of meltwater—might be hidden due to the complexity of feedback mechanisms that govern melt and runoff generation in such basins. Data scarcity adds to this difficulty by preventing the application of systematic calibration procedures that would allow identification of the parameter set that could guarantee internal consistency in the simulation of the single hydrological components. In this work, we use simulations from the Hunza River Basin in the Karakoram region obtained with the hydrological model TOPKAPI to quantify the predictive power of discharge and snow-cover data sets, as well as the combination of both. We also show that short-term measurements of meteorological variables such as radiative fluxes, wind speed, relative humidity, and air temperature from glacio-meteorological experiments are crucial for a correct parameterization of surface melt processes. They enable detailed simulations of the energy fluxes governing glacier–atmosphere interaction and the resulting ablation through energy-balance modeling. These simulations are used to derive calibrated parameters for the simplified snow and glacier routines in TOPKAPI. We demonstrate that such parameters are stable in space and time in similar climatic regions, thus reducing the number of parameters requiring calibration.}, author = {Pellicciotti, Francesca and Buergi, Cyrill and Immerzeel, Walter Willem and Konz, Markus and Shrestha, Arun B.}, issn = {1994-7151}, journal = {Mountain Research and Development}, number = {1}, pages = {39--50}, publisher = {International Mountain Society}, title = {{Challenges and uncertainties in hydrological modeling of remote Hindu Kush–Karakoram–Himalayan (HKH) basins: Suggestions for calibration strategies}}, doi = {10.1659/mrd-journal-d-11-00092.1}, volume = {32}, year = {2012}, } @article{12647, abstract = {Accurate quantification of the spatial distribution of precipitation in mountain regions is crucial for assessments of water resources and for the understanding of high-altitude hydrology, yet it is one of the largest unknowns due to the lack of high-altitude observations. The Hunza basin in Pakistan contains very large glacier systems, which, given the melt, cannot persist unless precipitation (snow input) is much higher than what is observed at the meteorological stations, mostly located in mountain valleys. Several studies, therefore, suggest strong positive vertical precipitation lapse rates; in the present study, we quantify this lapse rate by using glaciers as a proxy. We assume a neutral mass balance for the glaciers for the period from 2001 to 2003, and we inversely model the precipitation lapse by balancing the total accumulation in the catchment area and the ablation over the glacier area for the 50 largest glacier systems in the Hunza basin in the Karakoram. Our results reveal a vertical precipitation lapse rate that equals 0.21 ± 0.12% m−1, with a maximum precipitation at an elevation of 5500 masl. We showed that the total annual basin precipitation (828 mm) is 260% higher than what is estimated based on interpolated observations (319 mm); this has major consequences for hydrological modeling and water resource assessments in general. Our results were validated by using previously published studies on individual glaciers as well as the water balance of the Hunza basin. The approach is more widely applicable in mountain ranges where precipitation measurements at high altitude are lacking.}, author = {Immerzeel, Walter Willem and Pellicciotti, Francesca and Shrestha, Arun B.}, issn = {1994-7151}, journal = {Mountain Research and Development}, keywords = {General Environmental Science, Development, Environmental Chemistry}, number = {1}, pages = {30--38}, publisher = {International Mountain Society}, title = {{Glaciers as a proxy to quantify the spatial distribution of precipitation in the Hunza basin}}, doi = {10.1659/mrd-journal-d-11-00097.1}, volume = {32}, year = {2012}, } @article{12648, abstract = {Distributed glacier melt models generally assume that the glacier surface consists of bare exposed ice and snow. In reality, many glaciers are wholly or partially covered in layers of debris that tend to suppress ablation rates. In this paper, an existing physically based point model for the ablation of debris-covered ice is incorporated in a distributed melt model and applied to Haut Glacier d'Arolla, Switzerland, which has three large patches of debris cover on its surface. The model is based on a 10 m resolution digital elevation model (DEM) of the area; each glacier pixel in the DEM is defined as either bare or debris-covered ice, and may be covered in snow that must be melted off before ice ablation is assumed to occur. Each debris-covered pixel is assigned a debris thickness value using probability distributions based on over 1000 manual thickness measurements. Locally observed meteorological data are used to run energy balance calculations in every pixel, using an approach suitable for snow, bare ice or debris-covered ice as appropriate. The use of the debris model significantly reduces the total ablation in the debris-covered areas, however the precise reduction is sensitive to the temperature extrapolation used in the model distribution because air near the debris surface tends to be slightly warmer than over bare ice. Overall results suggest that the debris patches, which cover 10% of the glacierized area, reduce total runoff from the glacierized part of the basin by up to 7%.}, author = {Reid, T. D. and Carenzo, M. and Pellicciotti, Francesca and Brock, B. W.}, issn = {0148-0227}, journal = {Journal of Geophysical Research: Atmospheres}, keywords = {Paleontology, Space and Planetary Science, Earth and Planetary Sciences (miscellaneous), Atmospheric Science, Earth-Surface Processes, Geochemistry and Petrology, Soil Science, Water Science and Technology, Ecology, Aquatic Science, Forestry, Oceanography, Geophysics}, number = {D18}, publisher = {American Geophysical Union}, title = {{Including debris cover effects in a distributed model of glacier ablation}}, doi = {10.1029/2012jd017795}, volume = {117}, year = {2012}, } @misc{13075, abstract = {Little is known about the stability of trophic relationships in complex natural communities over evolutionary timescales. Here, we use sequence data from 18 nuclear loci to reconstruct and compare the intraspecific histories of major Pleistocene refugial populations in the Middle East, the Balkans and Iberia in a guild of four Chalcid parasitoids (Cecidostiba fungosa, C. semifascia, Hobbya stenonota and Mesopolobus amaenus) all attacking Cynipid oak galls. We develop a likelihood method to numerically estimate models of divergence between three populations from multilocus data. We investigate the power of this framework on simulated data, and - using triplet alignments of intronic loci - quantify the support for all possible divergence relationships between refugial populations in the four parasitoids. Although an East to West order of population divergence has highest support in all but one species, we cannot rule out alternative population tree topologies. Comparing the estimated times of population splits between species, we find that one species, M. amaenus, has a significantly older history than the rest of the guild and must have arrived in central Europe at least one glacial cycle prior to other guild members. This suggests that although all four species may share a common origin in the East, they expanded westwards into Europe at different times.}, author = {Lohse, Konrad and Barton, Nicholas H and Stone, Graham and Melika, George}, publisher = {Dryad}, title = {{Data from: A likelihood-based comparison of population histories in a parasitoid guild}}, doi = {10.5061/DRYAD.0G0FS}, year = {2012}, } @article{8246, abstract = {The Staphylococcus aureus cell wall stress stimulon (CWSS) is activated by cell envelope-targeting antibiotics or depletion of essential cell wall biosynthesis enzymes. The functionally uncharacterized S. aureus LytR-CpsA-Psr (LCP) proteins, MsrR, SA0908 and SA2103, all belong to the CWSS. Although not essential, deletion of all three LCP proteins severely impairs cell division. We show here that VraSR-dependent CWSS expression was up to 250-fold higher in single, double and triple LCP mutants than in wild type S. aureus in the absence of external stress. The LCP triple mutant was virtually depleted of wall teichoic acids (WTA), which could be restored to different degrees by any of the single LCP proteins. Subinhibitory concentrations of tunicamycin, which inhibits the first WTA synthesis enzyme TarO (TagO), could partially complement the severe growth defect of the LCP triple mutant. Both of the latter findings support a role for S. aureus LCP proteins in late WTA synthesis, as in Bacillus subtilis where LCP proteins were recently proposed to transfer WTA from lipid carriers to the cell wall peptidoglycan. Intrinsic activation of the CWSS upon LCP deletion and the fact that LCP proteins were essential for WTA-loading of the cell wall, highlight their important role(s) in S. aureus cell envelope biogenesis.}, author = {Dengler, Vanina and Meier, Patricia Stutzmann and Heusser, Ronald and Kupferschmied, Peter and Fazekas, Judit and Friebe, Sarah and Staufer, Sibylle Burger and Majcherczyk, Paul A. and Moreillon, Philippe and Berger-Bächi, Brigitte and McCallum, Nadine}, issn = {0378-1097}, journal = {FEMS Microbiology Letters}, number = {2}, pages = {109--120}, publisher = {Oxford University Press}, title = {{Deletion of hypothetical wall teichoic acid ligases in Staphylococcus aureus activates the cell wall stress response}}, doi = {10.1111/j.1574-6968.2012.02603.x}, volume = {333}, year = {2012}, } @article{826, abstract = {Plants exhibit a unique developmental flexibility to ever-changing environmental conditions. To achieve their profound adaptability, plants are able to maintain permanent stem cell populations and form new organs during the entire plant life cycle. Signaling substances, called plant hormones, such as auxin, cytokinin, abscisic acid, brassinosteroid, ethylene, gibberellin, jasmonic acid, and strigolactone, govern and coordinate these developmental processes. Physiological and genetic studies have dissected the molecular components of signal perception and transduction of the individual hormonal pathways. However, over recent years it has become evident that hormones do not act only in a linear pathway. Hormonal pathways are interconnected by a complex network of interactions and feedback circuits that determines the final outcome of the individual hormone actions. This raises questions about the molecular mechanisms underlying hormonal cross talk and about how these hormonal networks are established, maintained, and modulated throughout plant development.}, author = {Vanstraelen, Marleen and Eva Benková}, journal = {Annual Review of Cell and Developmental Biology}, pages = {463 -- 487}, publisher = {Annual Reviews}, title = {{Hormonal interactions in the regulation of plant development}}, doi = {10.1146/annurev-cellbio-101011-155741}, volume = {28}, year = {2012}, } @article{829, abstract = {The architecture of a plant's root system, established postembryonically, results from both coordinated root growth and lateral root branching. The plant hormones auxin and cytokinin are central endogenous signaling molecules that regulate lateral root organogenesis positively and negatively, respectively. Tight control and mutual balance of their antagonistic activities are particularly important during the early phases of lateral root organogenesis to ensure continuous lateral root initiation (LRI) and proper development of lateral root primordia (LRP). Here, we show that the early phases of lateral root organogenesis, including priming and initiation, take place in root zones with a repressed cytokinin response. Accordingly, ectopic overproduction of cytokinin in the root basal meristem most efficiently inhibits LRI. Enhanced cytokinin responses in pericycle cells between existing LRP might restrict LRI near existing LRP and, when compromised, ectopic LRI occurs. Furthermore, our results demonstrate that young LRP are more sensitive to perturbations in the cytokinin activity than are developmentally more advanced primordia. We hypothesize that the effect of cytokinin on the development of primordia possibly depends on the robustness and stability of the auxin gradient.}, author = {Bielach, Agnieszka and Podlesakova, Katerina and Peter Marhavy and Duclercq, Jérôme and Candela Cuesta and Muller, Bruno and Grunewald, Wim and Tarkowski, Petr and Eva Benková}, journal = {The Plant Cell}, number = {10}, pages = {3967 -- 3981}, publisher = {American Society of Plant Biologists}, title = {{Spatiotemporal regulation of lateral root organogenesis in Arabidopsis by cytokinin}}, doi = {10.1105/tpc.112.103044}, volume = {24}, year = {2012}, } @article{846, abstract = {Whether or not evolutionary change is inherently irreversible remains a controversial topic. Some examples of evolutionary irreversibility are known; however, this question has not been comprehensively addressed at the molecular level. Here, we use data from 221 human genes with known pathogenic mutations to estimate the rate of irreversibility in protein evolution. For these genes, we reconstruct ancestral amino acid sequences along the mammalian phylogeny and identify ancestral amino acid states that match known pathogenic mutations. Such cases represent inherent evolutionary irreversibility because, at the present moment, reversals to these ancestral amino acid states are impossible for the human lineage. We estimate that approximately 10% of all amino acid substitutions along the mammalian phylogeny are irreversible, such that a return to the ancestral amino acid state would lead to a pathogenic phenotype. For a subset of 51 genes with high rates of irreversibility, as much as 40% of all amino acid evolution was estimated to be irreversible. Because pathogenic phenotypes do not resemble ancestral phenotypes, the molecular nature of the high rate of irreversibility in proteins is best explained by evolution with a high prevalence of compensatory, epistatic interactions between amino acid sites. Under such mode of protein evolution, once an amino acid substitution is fixed, the probability of its reversal declines as the protein sequence accumulates changes that affect the phenotypic manifestation of the ancestral state. The prevalence of epistasis in evolution indicates that the observed high rate of irreversibility in protein evolution is an inherent property of protein structure and function.}, author = {Soylemez, Onuralp and Fyodor Kondrashov}, journal = {Genome Biology and Evolution}, number = {12}, pages = {1213 -- 1222}, publisher = {Oxford University Press}, title = {{Estimating the rate of irreversibility in protein evolution}}, doi = {10.1093/gbe/evs096}, volume = {4}, year = {2012}, } @article{8463, abstract = {The 1H dipolar network, which is the major obstacle for applying proton detection in the solid-state, can be reduced by deuteration, employing the RAP (Reduced Adjoining Protonation) labeling scheme, which yields random protonation at non-exchangeable sites. We present here a systematic study on the optimal degree of random sidechain protonation in RAP samples as a function of the MAS (magic angle spinning) frequency. In particular, we compare 1H sensitivity and linewidth of a microcrystalline protein, the SH3 domain of chicken α-spectrin, for samples, prepared with 5–25 % H2O in the E. coli growth medium, in the MAS frequency range of 20–60 kHz. At an external field of 19.96 T (850 MHz), we find that using a proton concentration between 15 and 25 % in the M9 medium yields the best compromise in terms of sensitivity and resolution, with an achievable average 1H linewidth on the order of 40–50 Hz. Comparing sensitivities at a MAS frequency of 60 versus 20 kHz, a gain in sensitivity by a factor of 4–4.5 is observed in INEPT-based 1H detected 1D 1H,13C correlation experiments. In total, we find that spectra recorded with a 1.3 mm rotor at 60 kHz have almost the same sensitivity as spectra recorded with a fully packed 3.2 mm rotor at 20 kHz, even though ~20× less material is employed. The improved sensitivity is attributed to 1H line narrowing due to fast MAS and to the increased efficiency of the 1.3 mm coil.}, author = {Asami, Sam and Szekely, Kathrin and Schanda, Paul and Meier, Beat H. and Reif, Bernd}, issn = {0925-2738}, journal = {Journal of Biomolecular NMR}, number = {2}, pages = {155--168}, publisher = {Springer Nature}, title = {{Optimal degree of protonation for 1H detection of aliphatic sites in randomly deuterated proteins as a function of the MAS frequency}}, doi = {10.1007/s10858-012-9659-9}, volume = {54}, year = {2012}, } @article{8465, abstract = {We demonstrate that conformational exchange processes in proteins on microsecond-to-millisecond time scales can be detected and quantified by solid-state NMR spectroscopy. We show two independent approaches that measure the effect of conformational exchange on transverse relaxation parameters, namely Carr–Purcell–Meiboom–Gill relaxation-dispersion experiments and measurement of differential multiple-quantum coherence decay. Long coherence lifetimes, as required for these experiments, are achieved by the use of highly deuterated samples and fast magic-angle spinning. The usefulness of the approaches is demonstrated by application to microcrystalline ubiquitin. We detect a conformational exchange process in a region of the protein for which dynamics have also been observed in solution. Interestingly, quantitative analysis of the data reveals that the exchange process is more than 1 order of magnitude slower than in solution, and this points to the impact of the crystalline environment on free energy barriers.}, author = {Tollinger, Martin and Sivertsen, Astrid C. and Meier, Beat H. and Ernst, Matthias and Schanda, Paul}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {36}, pages = {14800--14807}, publisher = {American Chemical Society}, title = {{Site-resolved measurement of microsecond-to-millisecond conformational-exchange processes in proteins by solid-state NMR spectroscopy}}, doi = {10.1021/ja303591y}, volume = {134}, year = {2012}, } @article{8466, abstract = {Recent advances in NMR spectroscopy and the availability of high magnetic field strengths now offer the possibility to record real-time 3D NMR spectra of short-lived protein states, e.g., states that become transiently populated during protein folding. Here we present a strategy for obtaining sequential NMR assignments as well as atom-resolved information on structural and dynamic features within a folding intermediate of the amyloidogenic protein β2-microglobulin that has a half-lifetime of only 20 min.}, author = {Rennella, Enrico and Cutuil, Thomas and Schanda, Paul and Ayala, Isabel and Forge, Vincent and Brutscher, Bernhard}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {19}, pages = {8066--8069}, publisher = {American Chemical Society}, title = {{Real-time NMR characterization of structure and dynamics in a transiently populated protein folding intermediate}}, doi = {10.1021/ja302598j}, volume = {134}, year = {2012}, } @article{8467, abstract = {Partial deuteration is a powerful tool to increase coherence life times and spectral resolution in proton solid-state NMR. The J coupling to deuterium needs, however, to be decoupled to maintain the good resolution in the (usually indirect) 13C dimension(s). We present a simple and reversible way to expand a commercial 1.3 mm HCN MAS probe with a 2H channel with sufficient field strength for J-decoupling of deuterium, namely 2–3 kHz. The coil is placed at the outside of the stator and requires no significant modifications to the probe. The performance and the realizable gains in sensitivity and resolution are demonstrated using perdeuterated ubiquitin, with selectively CHD2-labeled methyl groups.}, author = {Huber, Matthias and With, Oliver and Schanda, Paul and Verel, René and Ernst, Matthias and Meier, Beat H.}, issn = {1090-7807}, journal = {Journal of Magnetic Resonance}, pages = {76--80}, publisher = {Elsevier}, title = {{A supplementary coil for 2H decoupling with commercial HCN MAS probes}}, doi = {10.1016/j.jmr.2011.10.010}, volume = {214}, year = {2012}, } @article{8502, abstract = {The famous ergodic hypothesis suggests that for a typical Hamiltonian on a typical energy surface nearly all trajectories are dense. KAM theory disproves it. Ehrenfest (The Conceptual Foundations of the Statistical Approach in Mechanics. Ithaca, NY: Cornell University Press, 1959) and Birkhoff (Collected Math Papers. Vol 2, New York: Dover, pp 462–465, 1968) stated the quasi-ergodic hypothesis claiming that a typical Hamiltonian on a typical energy surface has a dense orbit. This question is wide open. Herman (Proceedings of the International Congress of Mathematicians, Vol II (Berlin, 1998). Doc Math 1998, Extra Vol II, Berlin: Int Math Union, pp 797–808, 1998) proposed to look for an example of a Hamiltonian near H0(I)=⟨I,I⟩2 with a dense orbit on the unit energy surface. In this paper we construct a Hamiltonian H0(I)+εH1(θ,I,ε) which has an orbit dense in a set of maximal Hausdorff dimension equal to 5 on the unit energy surface.}, author = {Kaloshin, Vadim and Saprykina, Maria}, issn = {0010-3616}, journal = {Communications in Mathematical Physics}, keywords = {Mathematical Physics, Statistical and Nonlinear Physics}, number = {3}, pages = {643--697}, publisher = {Springer Nature}, title = {{An example of a nearly integrable Hamiltonian system with a trajectory dense in a set of maximal Hausdorff dimension}}, doi = {10.1007/s00220-012-1532-x}, volume = {315}, year = {2012}, } @article{8503, abstract = {We prove there are finitely many isometry classes of planar central configurations (also called relative equilibria) in the Newtonian 5-body problem, except perhaps if the 5-tuple of positive masses belongs to a given codimension 2 subvariety of the mass space.}, author = {Albouy, Alain and Kaloshin, Vadim}, issn = {0003-486X}, journal = {Annals of Mathematics}, number = {1}, pages = {535--588}, publisher = {Princeton University Press}, title = {{Finiteness of central configurations of five bodies in the plane}}, doi = {10.4007/annals.2012.176.1.10}, volume = {176}, year = {2012}, } @article{8504, abstract = {In this paper we present a surprising example of a Cr unimodal map of an interval f:I→I whose number of periodic points Pn(f)=∣{x∈I:fnx=x}∣ grows faster than any ahead given sequence along a subsequence nk=3k. This example also shows that ‘non-flatness’ of critical points is necessary for the Martens–de Melo–van Strien theorem [M. Martens, W. de Melo and S. van Strien. Julia–Fatou–Sullivan theory for real one-dimensional dynamics. Acta Math.168(3–4) (1992), 273–318] to hold.}, author = {Kaloshin, Vadim and KOZLOVSKI, O. S.}, issn = {0143-3857}, journal = {Ergodic Theory and Dynamical Systems}, keywords = {Applied Mathematics, General Mathematics}, number = {1}, pages = {159--165}, publisher = {Cambridge University Press}, title = {{A Cr unimodal map with an arbitrary fast growth of the number of periodic points}}, doi = {10.1017/s0143385710000817}, volume = {32}, year = {2012}, } @article{858, abstract = {ackground: The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes.Results: We show that in bacteria stop codons evolve slower than synonymous sites, suggesting the action of weak negative selection. However, the frequency of stop codons relative to genomic nucleotide content indicated that this selection regime is not straightforward. The frequency of TAA and TGA stop codons is GC-content dependent, with TAA decreasing and TGA increasing with GC-content, while TAG frequency is independent of GC-content. Applying a formal, analytical model to these data we found that the relationship between stop codon frequencies and nucleotide content cannot be explained by mutational biases or selection on nucleotide content. However, with weak nucleotide content-dependent selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and recapitulates the relationship between TAG and nucleotide content. For biologically plausible rates of mutations we show that, in bacteria, TAG stop codon is universally associated with lower fitness, with TAA being the optimal for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG.Conclusions: Our data indicate that TAG codon is universally suboptimal in the bacterial lineage, such that TAA is likely to be the preferred stop codon for low GC content while the TGA is the preferred stop codon for high GC content. The optimization of stop codon usage may therefore be useful in genome engineering or gene expression optimization applications.Reviewers: This article was reviewed by Michail Gelfand, Arcady Mushegian and Shamil Sunyaev. For the full reviews, please go to the Reviewers' Comments section.}, author = {Povolotskaya, Inna and Fyodor Kondrashov and Ledda, Alice and Vlasov, Peter K}, journal = {Biology Direct}, publisher = {BioMed Central}, title = {{Stop codons in bacteria are not selectively equivalent}}, doi = {10.1186/1745-6150-7-30}, volume = {7}, year = {2012}, } @article{887, abstract = {A subject of extensive study in evolutionary theory has been the issue of how neutral, redundant copies can be maintained in the genome for long periods of time. Concurrently, examples of adaptive gene duplications to various environmental conditions in different species have been described. At this point, it is too early to tell whether or not a substantial fraction of gene copies have initially achieved fixation by positive selection for increased dosage. Nevertheless, enough examples have accumulated in the literature that such a possibility should be considered. Here, I review the recent examples of adaptive gene duplications and make an attempt to draw generalizations on what types of genes may be particularly prone to be selected for under certain environmental conditions. The identification of copy-number variation in ecological field studies of species adapting to stressful or novel environmental conditions may improve our understanding of gene duplications as a mechanism of adaptation and its relevance to the long-term persistence of gene duplications.}, author = {Fyodor Kondrashov}, journal = {Proceedings of the Royal Society of London Series B Biological Sciences}, number = {1749}, pages = {5048 -- 5057}, publisher = {Royal Society, The}, title = {{Gene duplication as a mechanism of genomic adaptation to a changing environment}}, doi = {10.1098/rspb.2012.1108}, volume = {279}, year = {2012}, } @article{900, abstract = {The main forces directing long-term molecular evolution remain obscure. A sizable fraction of amino-acid substitutions seem to be fixed by positive selection, but it is unclear to what degree long-term protein evolution is constrained by epistasis, that is, instances when substitutions that are accepted in one genotype are deleterious in another. Here we obtain a quantitative estimate of the prevalence of epistasis in long-term protein evolution by relating data on amino-acid usage in 14 organelle proteins and 2 nuclear-encoded proteins to their rates of short-term evolution. We studied multiple alignments of at least 1,000 orthologues for each of these 16 proteins from species from a diverse phylogenetic background and found that an average site contained approximately eight different amino acids. Thus, without epistasis an average site should accept two-fifths of all possible amino acids, and the average rate of amino-acid substitutions should therefore be about three-fifths lower than the rate of neutral evolution. However, we found that the measured rate of amino-acid substitution in recent evolution is 20 times lower than the rate of neutral evolution and an order of magnitude lower than that expected in the absence of epistasis. These data indicate that epistasis is pervasive throughout protein evolution: about 90 per cent of all amino-acid substitutions have a neutral or beneficial impact only in the genetic backgrounds in which they occur, and must therefore be deleterious in a different background of other species. Our findings show that most amino-acid substitutions have different fitness effects in different species and that epistasis provides the primary conceptual framework to describe the tempo and mode of long-term protein evolution.}, author = {Breen, Michael S and Kemena, Carsten and Vlasov, Peter K and Notredame, Cédric and Fyodor Kondrashov}, journal = {Nature}, number = {7421}, pages = {535 -- 538}, publisher = {Nature Publishing Group}, title = {{Epistasis as the primary factor in molecular evolution}}, doi = {10.1038/nature11510}, volume = {490}, year = {2012}, }