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Before senescence: the evolutionary demography of ontogenesis
Daniel A. Levitis*
+Author Affiliations
Laboratory of Evolutionary Biodemography, Max Planck Institute for Demographic Research, Konrad-Zuse-Strasse 1, 18057 Rostock, Germany
* levitis@demogr.mpg.de
Abstract
The age-specific mortality curve for many species, including humans, is U-shaped: mortality declines with age in the developing cohort (ontogenescence) before increasing with age (senescence). The field of evolutionary demography has long focused on understanding the evolution of senescence while largely failing to address the evolution of ontogenescence. The current review is the first to gather the few available hypotheses addressing the evolution of ontogenescence, examine the basis and assumptions of each and ask what the phylogenetic extent of ontogenescence may be. Ontogenescence is among the most widespread of life-history traits, occurring in every population for which I have found sufficiently detailed data, in major groups throughout the eukaryotes, across many causes of death and many life-history types. Hypotheses seeking to explain ontogenescence include those based on kin selection, the acquisition of robustness, heterogeneous frailties and life-history optimization. I propose a further hypothesis, arguing that mortality drops with age because most transitions that could trigger the risks caused by genetic and developmental malfunctions are concentrated in early life. Of these hypotheses, only those that frame ontogenescence as an evolutionary by-product rather than an adaptation can explai


Science 11 February 2011: 
Vol. 331 no. 6018 pp. 728-729 
DOI: 10.1126/science.1197891
PERSPECTIVE
On the Future of Genomic Data
Scott D. Kahn
+Author Affiliations
Illumina, 9885 Towne Centre Drive, San Diego, CA 92121, USA.
ABSTRACT
Many of the challenges in genomics derive from the informatics needed to store and analyze the raw sequencing data that is available from highly multiplexed sequencing technologies. Because single week-long sequencing runs today can produce as much data as did entire genome centers a few years ago, the need to process terabytes of information has become de rigueur for many labs engaged in genomic research. The availability of deep (and large) genomic data sets raises concerns over information access, data security, and subject/patient privacy that must be addressed for the field to continue its rapid advances.

Changing the Equation on Scientific Data Visualization
Peter Fox and 
James Hendler*
+Author Affiliations
Tetherless World Constellation, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
*To whom correspondence should be addressed. E-mail: hendler@cs.rpi.edu
ABSTRACT
An essential facet of the data deluge is the need for different types of users to apply visualizations to understand how data analyses and queries relate to each other. Unfortunately, visualization too often becomes an end product of scientific analysis, rather than an exploration tool that scientists can use throughout the research life cycle. However, new database technologies, coupled with emerging Web-based technologies, may hold the key to lowering the cost of visualization generation and allow it to become a more integral part of the scientific process.Science 11 February 2011: 
Vol. 331 no. 6018 pp. 694-695 
DOI: 10.1126/science.331.6018.694
NEWS
NEWS
Rescue of Old Data Offers Lesson for Particle Physicists
Andrew Curry*
Accustomed to working in large collaborations and moving swiftly on to bigger, better machines, particle physicists have no standard format for sharing or storing information after an experiment shuts down. Old data can end up scattered across the globe, stored haphazardly on old tapes, or lost entirely. This tendency has prompted some in the field to call for better care to be taken of data after an experiment has finished. For a very small fraction of the experiment's budget, they argue, data could be preserved in a form usable by later generations of physicists. To promote this strategy, researchers from a half-dozen major labs around the world, including CERN, formed a working group in 2009 called Data Preservation in High Energy Physics. One of the group's aims is to create the new post of "data archivist," someone within each experimental team who will ensure that information is properly managed.

	 
GENOME ANNOUNCEMENT
Genome Sequence of Leuconostoc inhae KCTC 3774, Isolated from Kimchi 
Dae-Soo Kim,1, Sang-Haeng Choi,1, Dong-Wook Kim,1 Ryong Nam Kim,1Seong-Hyeuk Nam,1 Aram Kang,1,2 Aeri Kim,1,2 and Hong-Seog Park1,2*
Genome Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 111 Gwahangno, Yuseong-gu, Daejeon 305-806, Republic of Korea,1 University of Science and Technology (UST), 113 Gwahangno, Yuseong-gu, Daejeon 305-806, Republic of Korea2
Received 1 December 2010/ Accepted 13 December 2010
ABSTRACT
Leuconostoc inhae strain KCTC 3774 is a Gram-positive, non-spore-forming,heterofermentative, spherical or lenticular lactic acid bacterium. Here we announce the draft genome sequence of Leuconostoc inhae KCTC 3774, isolated from traditional Korean kimchi, and describe major findings from its annotation.
Journal of Bacteriology, March 2011, p. 1183-1190, Vol. 193, No. 5
0021-9193/11/$12.00+0     doi:10.1128/JB.00925-10
Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Complete Genome Sequence of the Metabolically Versatile Plant Growth-Promoting EndophyteVariovorax paradoxus S110  ,
Jong-In Han,1,* Hong-Kyu Choi,2, Seung-Won Lee,11,3 Paul M. Orwin,4Jina Kim,1 Sarah L. LaRoe,5 Tae-gyu Kim,1 Jennifer O'Neil,5 Jared R. Leadbetter,6 Sang Yup Lee,7 Cheol-Goo Hur,3 Jim C. Spain,8 Galina Ovchinnikova,9 Lynne Goodwin,10 and Cliff Han10
Department of Civil and Environmental Engineering, KAIST, Daejeon, Republic of Korea,1 Department of Genetic Engineering, Dong-A University, Busan, Republic of Korea,2 Bioinformatics Research Center, KRIBB, Daejeon, Republic of Korea,3 California State University at San Bernardino, Department of Biology, San Bernardino, California,4 Department of Civil and Environmental Engineering, Rensselaer Polytechnic Institute, 110 8th St., Troy, New York,5Divisions of Biology and Environmental Science and Engineering, California Institute of Technology, Pasadena, California,6 Department of Chemical and Biomolecular Engineering, KAIST, Daejeon, Republic of Korea,7 School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, Georgia,8 DOE Joint Genome Institute, Walnut Creek, California,9 Los Alamos National Laboratory, Los Alamos, New Mexico,10 Department of Agricultural Bio-Resources, Genomics Division, National Academy of Agricultural Science, Suwon, Republic of Korea,11
Received 7 August 2010/ Accepted 11 November 2010
Variovorax paradoxus is a microorganism of special interest due to its diverse metabolic capabilities, including the biodegradation of both biogenic compounds and anthropogenic contaminants. V. paradoxus also engages in mutually beneficial interactions with both bacteria and plants. The complete genome sequence of V. paradoxus S110 is composed of 6,754,997 bp with 6,279 predicted protein-coding sequences within two circular chromosomes. Genomicanalysis has revealed multiple metabolic features for autotrophic and heterotrophic lifestyles. These metabolic diversities enable independent survival, as well as a symbiotic lifestyle. Consequently, S110 appears to have evolved into a superbly adaptable microorganism that is able to survive in ever-changing environmental conditions. Based on our findings, we suggest V. paradoxus S110 as a potential candidate for agrobiotechnological applications, such as biofertilizer and biopesticide. Because it has many associations with other biota, it is also suited to serve as an additional model system for studies of microbe-plant and microbe-microbe interactions.
      
Article alert
The latest articles from Biology Direct, published between 27-Jan-2011 and 09-Feb-2011
Discovery notes
Evolutionary patterns of phosphorylated serines
Yerbol Z Kurmangaliyev1,2 , Alexander Goland1  and Mikhail S Gelfand1,3 
1 Institute for Information Transmission Problems (the Kharkevich Institute) RAS, Bolshoi Karetny pereulok 19, Moscow, 127994, Russia
2 National Center for Biotechnology of the Republic of Kazakhstan, Valikhanov str., 13/1, Astana, 010000, Republic of Kazakhstan
3 Faculty of Bioengineering and Bioinformatics, Moscow State University, Vorobievy Gory 1-73, Moscow, 119991, Russia
 author email corresponding author email
Biology Direct 2011, 6:8doi:10.1186/1745-6150-6-8
Published:
9 February 2011
Abstract
Posttranslationally modified amino acids are chemically distinct types of amino acids and in terms of evolution they might behave differently from their non-modified counterparts. In order to check this possibility, we reconstructed the evolutionary history of phosphorylated serines in several groups of organisms. Comparisons of substitution vectors have revealed some significant differences in the evolution of modified and corresponding non-modified amino acids. In particular, phosphoserines are more frequently substituted to aspartate and glutamate, compared to non-phosphorylated serines.
Research
Gene gain and loss events in Rickettsia and Orientia species
Kalliopi Georgiades , Vicky Merhej , Khalid El Karkouri , Didier Raoult  and Pierre Pontarotti 
Biology Direct 2011, 6:6doi:10.1186/1745-6150-6-6
Published:
8 February 2011
Abstract (provisional)
Background
Genome degradation is an ongoing process in all members of the Rickettsiales order, which makes these bacterial species an excellent model for studying reductive evolution through interspecies variation in genome size and gene content. In this study, we evaluated the degree to which gene loss shaped the content of some Rickettsiales genomes. We shed light on the role played by horizontal gene transfers in the genome evolution of Rickettsiales.
Results
Our phylogenomic tree, based on whole-genome content, presented a topology distinct from that of the whole core gene concatenated phylogenetic tree, suggesting that the gene repertoires involved have different evolutionary histories. Indeed, we present evidence for 3 possible horizontal gene transfer events from various organisms to Orientia and 6 to Rickettsia spp., while we also identified 3 possible horizontal gene transfer events from Rickettsia and Orientia to other bacteria. We found 17 putative genes in Rickettsia spp. that are probably the result of de novo gene creation; 2 of these genes appear to be functional. On the basis of these results, we were able to reconstruct the gene repertoires of "proto-Rickettsiales" and "proto-Rickettsiaceae", which correspond to the ancestors of Rickettsiales and Rickettsiaceae, respectively. Finally, we found that 2,135 genes were lost during the evolution of the Rickettsiaceae to an intracellular lifestyle.
Conclusions
Our phylogenetic analysis allowed us to track the gene gain and loss events occurring in bacterial genomes during their evolution from a free-living to an intracellular lifestyle. We have shown that the primary mechanism of evolution and specialization in strictly intracellular bacteria is gene loss. Despite the intracellular habitat, we found several horizontal gene transfers between Rickettsiales species and various prokaryotic, viral and eukaryotic species. Open peer review: Reviewed by Arcady Mushegian, Eugene V. Koonin and Patrick Forterre. For the full reviews please go to the Reviewers' comments section.

Opinion
The Multiple Personalities of Watson and Crick Strands
Reed A Cartwright  and Dan Graur 
Biology Direct 2011, 6:7doi:10.1186/1745-6150-6-7
Published:
8 February 2011
Abstract (provisional)
Background
In genetics it is customary to refer to double-stranded DNA as containing a 'Watson strand' and a 'Crick strand.' However, there seems to be no consensus in the literature on the exact meaning of these two terms, and the many usages contradict one another as well as the original definition. Here, we review the history of the terminology and suggest retaining a single sense that is currently the most useful and consistent. Proposal: The Saccharomyces Genome Database defines the Watson strand as the strand which has its 5'-end at the short-arm telomere and the Crick strand as its complement. The Watson strand is always used as the reference strand in their database. Using this as the basis of our standard, we recommend that Watson and Crick strand terminology only be used in the context of genomics. When possible, the centromere or other genomic feature should be used as a reference point, dividing the chromosome into two arms of unequal lengths. Under our proposal, the Watson strand is standardized as the strand whose 5'-end is on the short arm of the chromosome, and the Crick strand as the one whose 5'-end is on the long arm. Furthermore, the Watson strand should be retained as the reference (plus) strand in a genomic database. This usage not only makes the determination of Watson and Crick unambiguous but also allows unambiguous selection of reference stands for genomics. Reviewers: This article was reviewed by John M. Logsdon, Igor B. Rogozin (nominated by Andrey Rzhetsky), and William Martin.

Mechanism for the Alteration of the Substrate Specificities of Template-Independent RNA Polymerases
Summary
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Structure, Volume 19, Issue 2, 232-243, 9 February 2011
Copyright © 2011 Elsevier Ltd All rights reserved.
10.1016/j.str.2010.12.006
 
Authors
Yukimatsu Toh,Daijiro Takeshita,Takashi Nagaike,Tomoyuki Numata,Kozo TomitaSee Affiliations
Highlights
Crystal structure of eubacterial polyA polymerase and its complex with ATP
The size and shape of the nucleobase interacting pocket are suitable for only ATP
The RNA-binding and catalytic domains together dictate the substrate specificity of polyA polymerase
The mechanism of ATP selection by polyA polymerase is distinct from that by the CCA-adding enzyme
Summary
PolyA polymerase (PAP) adds a polyA tail onto the 3′-end of RNAs without a nucleic acid template, using adenosine-5′-triphosphate (ATP) as a substrate. The mechanism for the substrate selection by eubacterial PAP remains obscure. Structural and biochemical studies of Escherichia coli PAP (EcPAP) revealed that the shape and size of the nucleobase-interacting pocket of EcPAP are maintained by an intra-molecular hydrogen-network, making it suitable for the accommodation of only ATP, using a single amino acid, Arg197. The pocket structure is sustained by interactions between the catalytic domain and the RNA-binding domain. EcPAP has a flexible basic C-terminal region that contributes to optimal RNA translocation for processive adenosine 5′-monophosphate (AMP) incorporations onto the 3′-end of RNAs. A comparison of the EcPAP structure with those of other template-independent RNA polymerases suggests that structural changes of domain(s) outside the conserved catalytic core domain altered the substrate specificities of the template-independent RNA polymerases.
PNAS Online Table of Contents Alert
A new issue of Proceedings of the National Academy of Sciences is available online:
8 February 2011; Vol. 108, No. 6 

The below Table of Contents is available online at: http://www.pnas.org/content/vol108/issue6/?etoc
Genome and transcriptome analyses of the mountain pine beetle-fungal symbiontGrosmannia clavigera, a lodgepole pine pathogen
Scott DiGuistinia, 
Ye Wanga, 
Nancy Y. Liaob, 
Greg Taylorb,
Philippe Tanguayc, 
Nicolas Feaud, 
Bernard Henrissate, 
Simon K. Chanb,
Uljana Hesse-Orcea, 
Sepideh Massoumi Alamoutia, 
Clement K. M. Tsuif,
Roderick T. Dockingb, 
Anthony Levasseurg, 
Sajeet Haridasa,
Gordon Robertsonb, 
Inanc Birolb, 
Robert A. Holtb, 
Marco A. Marrab,
Richard C. Hamelinc, 
Martin Hirstb, 
Steven J. M. Jonesb, 
Jörg Bohlmannf,h,1, and 
Colette Breuila,1
+Author Affiliations
aDepartment of Wood Science,
fDepartment of Forest Science, University of British Columbia, Vancouver, BC, Canada V6T 1Z4;
bBritish Columbia Cancer Agency Genome Sciences Centre, Vancouver, BC, Canada V5Z 4E6;
cNatural Resources Canada, Ste-Foy, QC, Canada G1V 4C7;
dUnité Mixte de Recherche 1202, Institut National de la Recherche Agronomique-Université Bordeaux I, Biodiversité, Gènes et Communautés, Institut National de la Recherche Agronomique Bordeaux-Aquitaine, 33612 Cestas Cedex, France;
eArchitecture et Fonction des Macromolécules Biologiques, Unité Mixte de Recherche-6098, Centre National de la Recherche Scientifique, Universités Aix-Marseille I & II, 13288 Marseille cedex 9, France;
gBiotechnologie des Champignons Filamenteux, Unité Mixte de Recherche-1161, Institut National de la Recherche, Universités de Provence et de la Méditerranée, 13288 Marseille cedex 09, France; and
hMichael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
Edited by Rodney B. Croteau, Washington State University, Pullman, WA, and approved December 27, 2010 (received for review August 2, 2010)
Abstract
In western North America, the current outbreak of the mountain pine beetle (MPB) and its microbial associates has destroyed wide areas of lodgepole pine forest, including more than 16 million hectares in British Columbia. Grosmannia clavigera (Gc), a critical component of the outbreak, is a symbiont of the MPB and a pathogen of pine trees. To better understand the interactions between Gc, MPB, and lodgepole pine hosts, we sequenced the ∼30-Mb Gc genome and assembled it into 18 supercontigs. We predict 8,314 protein-coding genes, and support the gene models with proteome, expressed sequence tag, and RNA-seq data. We establish that Gc is heterothallic, and report evidence for repeat-induced point mutation. We report insights, from genome and transcriptome analyses, into how Gc tolerates conifer-defense chemicals, including oleoresin terpenoids, as they colonize a host tree. RNA-seq data indicate that terpenoids induce a substantial antimicrobial stress in Gc, and suggest that the fungus may detoxify these chemicals by using them as a carbon source. Terpenoid treatment strongly activated a ∼100-kb region of the Gc genome that contains a set of genes that may be important for detoxification of these host-defense chemicals. This work is a major step toward understanding the biological interactions between the tripartite MPB/fungus/forest system.

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NAR Synthetic Biology Open Access Special Issue

A new open access special issue of NAR on Synthetic Biology is now available to read 
online: here. Edited by James J. Collins, Drew Endy, Clyde A. Hutchison III, 
and Richard J. Roberts, it details the many advances made in this dynamic area - 
including those at the intersections of chemistry, physics, biology and engineering. 

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Nucleic Acids Research Table of Contents Alert
A new issue of Nucleic Acids Research is available online:
Vol. 39, No. 3
The below Table of Contents is available online at: http://nar.oxfordjournals.org/content/vol39/issue3/index.dtl

Investigating the predictability of essential genes across distantly related organisms using an integrative approach
Jingyuan Deng1,2, 
Lei Deng1,3, 
Shengchang Su4, 
Minlu Zhang5, 
Xiaodong Lin6, 
Lan Wei7,
Ali A. Minai3, 
Daniel J. Hassett4 and 
Long J. Lu1,2,5,8,*
+Author Affiliations
1Division of Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation, Cincinnati, OH 45229, 2Department of Biomedical Engineering, 3Department of Electrical and Computer Engineering, 4Department of Molecular Genetics, Biochemistry and Microbiology, 5Department of Computer Science, University of Cincinnati, Cincinnati, OH 45229, 6Department of Management Science and Information Systems, Rutgers University, Piscataway, NJ 08854, 7School of Medicine, Yale University, New Haven, CT 06511 and 8Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45229, USA
*To whom correspondence should be addressed. Tel: +1 513 636 8720; Fax: +1 513 636 2056; Email: long.lu@cchmc.org
Received May 28, 2010.
Revision received August 15, 2010.
Accepted August 18, 2010.
Abstract
Rapid and accurate identification of new essential genes in under-studied microorganisms will significantly improve our understanding of how a cell works and the ability to re-engineer microorganisms. However, predicting essential genes across distantly related organisms remains a challenge. Here, we present a machine learning-based integrative approach that reliably transfers essential gene annotations between distantly related bacteria. We focused on four bacterial species that have well-characterized essential genes, and tested the transferability between three pairs among them. For each pair, we trained our classifier to learn traits associated with essential genes in one organism, and applied it to make predictions in the other. The predictions were then evaluated by examining the agreements with the known essential genes in the target organism. Ten-fold cross-validation in the same organism yielded AUC scores between 0.86 and 0.93. Cross-organism predictions yielded AUC scores between 0.69 and 0.89. The transferability is likely affected by growth conditions, quality of the training data set and the evolutionary distance. We are thus the first to report that gene essentiality can be reliably predicted using features trained and tested in a distantly related organism. Our approach proves more robust and portable than existing approaches, significantly extending our ability to predict essential genes beyond orthologs.
C-terminal domain of archaeal O-phosphoseryl-tRNA kinase displays large-scale motion to bind the 7-bp D-stem of archaeal tRNASec
R. Lynn Sherrer1, 
Yuhei Araiso2,3, 
Caroline Aldag1, 
Ryuichiro Ishitani2, 
Joanne M. L. Ho1,
Dieter Söll1,4,* and 
Osamu Nureki2,3,*
+Author Affiliations
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA, 2Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, 3Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan and 4Department of Chemistry, Yale University, New Haven, Connecticut 06520-8114, USA
*To whom correspondence should be addressed. Tel: +81 3 5841 4392; Fax: +81 3 5841 8057; Email: nureki@ims.u-tokyo.ac.jp
Correspondence may also be addressed to Dieter Söll. Tel: +1 203 432 6200; Fax: +1 203 432 6202; Email: dieter.Soll@yale.edu
Received August 17, 2010.
Revision received September 6, 2010.
Accepted September 8, 2010.
Abstract
O-Phosphoseryl-tRNA kinase (PSTK) is the key enzyme in recruiting selenocysteine (Sec) to the genetic code of archaea and eukaryotes. The enzyme phosphorylates Ser-tRNASec to produceO-phosphoseryl-tRNASec (Sep-tRNASec) that is then converted to Sec-tRNASec by Sep-tRNA:Sec-tRNA synthase. Earlier we reported the structure of the Methanocaldococcus jannaschii PSTK (MjPSTK) complexed with AMPPNP. This study presents the crystal structure (at 2.4-Å resolution) of MjPSTK complexed with an anticodon-stem/loop truncated tRNASec(Mj*tRNASec), a good enzyme substrate. Mj*tRNASec is bound between the enzyme’s C-terminal domain (CTD) and N-terminal kinase domain (NTD) that are connected by a flexible 11 amino acid linker. Upon Mj*tRNASec recognition the CTD undergoes a 62-Å movement to allow proper binding of the 7-bp D-stem. This large reorganization of the PSTK quaternary structure likely provides a means by which the unique tRNASec species can be accurately recognized with high affinity by the translation machinery. However, while the NTD recognizes the tRNA acceptor helix, shortened versions of MjPSTK (representing only 60% of the original size, in which the entire CTD, linker loop and an adjacent NTD helix are missing) are still activein vivo and in vitro, albeit with reduced activity compared to the full-length enzyme.

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Proofreading and spellchecking: A two-tier strategy for pre-mRNA splicing quality control
Defne E. Egecioglu1,2 and 
Guillaume Chanfreau1,2
+Author Affiliations
1Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California 90095-1569, USA
2Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095-1569, USA
Abstract
Multi-tier strategies exist in many biochemical processes to ensure a maximal fidelity of the reactions. In this review, we focus on the two-tier quality control strategy that ensures the quality of the products of the pre-mRNA splicing reactions catalyzed by the spliceosome. The first step in the quality control process relies on kinetic proofreading mechanisms that are internal to the spliceosome and that are performed by ATP-dependent RNA helicases. The second quality control step, spellchecking, involves recognition of unspliced pre-mRNAs or aberrantly spliced mRNAs that have escaped the first proofreading mechanisms, and subsequent degradation of these molecules by degradative enzymes in the nucleus or in the cytoplasm. This two-tier quality control strategy highlights a need for high fidelity and a requirement for degradative activities that eliminate defective molecules. The presence of multiple quality control activities during splicing underscores the importance of this process in the expression of genetic information.
Identification of compounds that decrease the fidelity of start codon recognition by the eukaryotic translational machinery
Julie E. Takacs1, 
Timothy B. Neary1, 
Nicholas T. Ingolia2,3,4,
Adesh K. Saini5, 
Pilar Martin-Marcos5, 
Jerry Pelletier6,
Alan G. Hinnebusch5 and 
Jon R. Lorsch1
+Author Affiliations
1Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
2Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, California 94158, USA
3California Institute for Quantitative Biosciences, San Francisco, California 94158, USA
4Department of Embryology, Carnegie Institution, Baltimore, Maryland 21218, USA
5Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
6Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada
Abstract
Translation initiation in eukaryotes involves more than a dozen protein factors. Alterations in six factors have been found to reduce the fidelity of start codon recognition by the ribosomal preinitiation complex in yeast, a phenotype referred to as Sui−. No small molecules are known that affect the fidelity of start codon recognition. Such compounds would be useful tools for probing the molecular mechanics of translation initiation and its regulation. To find compounds with this effect, we set up a high-throughput screen using a dual luciferase assay in S. cerevisiae. Screening of over 55,000 compounds revealed two structurally related molecules that decrease the fidelity of start codon selection by approximately twofold in the dual luciferase assay. This effect was confirmed using additional in vivo assays that monitor translation from non-AUG start codons. Both compounds increase translation of a natural upstream open reading frame previously shown to initiate translation at a UUG. The compounds were also found to exacerbate increased use of UUG as a start codon (Sui− phenotype) conferred by haploinsufficiency of wild-type eukaryotic initiation factor (eIF) 1, or by mutation in eIF1. Furthermore, the effects of the compounds are suppressed by overexpressing eIF1, which is known to restore the fidelity of start codon selection in strains harboring Sui− mutations in various other initiation factors. Together, these data strongly suggest that the compounds affect the translational machinery itself to reduce the accuracy of selecting AUG as the start codon.
Distinct regulatory programs establish widespread sex-specific alternative splicing in Drosophila melanogaster
Britta Hartmann1,2,3, 
Robert Castelo2,4, 
Belén Miñana1,2, 
Erin Peden5,
Marco Blanchette6,8, 
Donald C. Rio6, 
Ravinder Singh5 and
Juan Valcárcel7
+Author Affiliations
1Centre de Regulació Genòmica, Dr. Aiguader 88, 08003 Barcelona, Spain
2Universitat Pompeu Fabra, Dr. Aiguader 88, 08003 Barcelona, Spain
3Centre for Biological Signalling Studies (BIOSS), Albert-Ludwigs-Universitaät, Habsburgerstrasse 49, 79104 Freiburg, Germany
4Institut Municipal d'Investigació Mèdica, Dr. Aiguader 88, 08003 Barcelona, Spain
5Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA
6Department of Molecular and Cell Biology, University of California at Berkeley, California 94720-3204, USA
7Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain
↵8 Present address: Stowers Institute for Biomedical Research, Kansas City, MO 64110, USA.
Abstract
In Drosophila melanogaster, female-specific expression of Sex-lethal (SXL) and Transformer (TRA) proteins controls sex-specific alternative splicing and/or translation of a handful of regulatory genes responsible for sexual differentiation and behavior. Recent findings in 2009 by Telonis-Scott et al. document widespread sex-biased alternative splicing in fruitflies, including instances of tissue-restricted sex-specific splicing. Here we report results arguing that some of these novel sex-specific splicing events are regulated by mechanisms distinct from those established by female-specific expression of SXL and TRA. Bioinformatic analysis of SXL/TRA binding sites, experimental analysis of sex-specific splicing in S2 and Kc cells lines and of the effects of SXL knockdown in Kc cells indicate that SXL-dependent and SXL-independent regulatory mechanisms coexist within the same cell. Additional determinants of sex-specific splicing can be provided by sex-specific differences in the expression of RNA binding proteins, including Hrp40/Squid. We report that sex-specific alternative splicing of the gene hrp40/squid leads to sex-specific differences in the levels of this hnRNP protein. The significant overlap between sex-regulated alternative splicing changes and those induced by knockdown of hrp40/squidand the presence of related sequence motifs enriched near subsets of Hrp40/Squid-regulated and sex-regulated splice sites indicate that this protein contributes to sex-specific splicing regulation. A significant fraction of sex-specific splicing differences are absent in germline-less tudor mutant flies. Intriguingly, these include alternative splicing events that are differentially spliced in tissues distant from the germline. Collectively, our results reveal that distinct genetic programs control widespread sex-specific splicing in Drosophila melanogaster.

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Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19820-5. Epub 2010 Nov 1.
Stochastic reaction-diffusion kinetics in the microscopic limit.
Fange D, Berg OG, Sjöberg P, Elf J.
Department of Cell and Molecular Biology, Uppsala University, 75124 Uppsala, Sweden.
Abstract
Quantitative analysis of biochemical networks often requires consideration of both spatial and stochastic aspects of chemical processes. Despite significant progress in the field, it is still computationally prohibitive to simulate systems involving many reactants or complex geometries using a microscopic framework that includes the finest length and time scales of diffusion-limited molecular interactions. For this reason, spatially or temporally discretized simulations schemes are commonly used when modeling intracellular reaction networks. The challenge in defining such coarse-grained models is to calculate the correct probabilities of reaction given the microscopic parameters and the uncertainty in the molecular positions introduced by the spatial or temporal discretization. In this paper we have solved this problem for the spatially discretized Reaction-Diffusion Master Equation; this enables a seamless and physically consistent transition from the microscopic to the macroscopic frameworks of reaction-diffusion kinetics. We exemplify the use of the methods by showing that a phosphorylation-dephosphorylation mot
f, commonly observed in eukaryotic signaling pathways, is predicted to display fluctuations that depend on the geometry of the system.

Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):6946-51. Epub 2010 Mar 24.
Metabolic cycling in single yeast cells from unsynchronized steady-state populations limited on glucose or phosphate.
Silverman SJ, Petti AA, Slavov N, Parsons L, Briehof R, Thiberge SY, Zenklusen D, Gandhi SJ, Larson DR, Singer RH, Botstein D.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Abstract
Oscillations in patterns of expression of a large fraction of yeast genes are associated with the "metabolic cycle," usually seen only in prestarved, continuous cultures of yeast. We used FISH of mRNA in individual cells to test the hypothesis that these oscillations happen in single cells drawn from unsynchronized cultures growing exponentially in chemostats. Gene-expression data from synchronized cultures were used to predict coincident appearance of mRNAs from pairs of genes in the unsynchronized cells. Quantitative analysis of the FISH results shows that individual unsynchronized cells growing slowly because of glucose limitation or phosphate limitation show the predicted oscillations. We conclude that the yeast metabolic cycle is an intrinsic property of yeast metabolism and does not depend on either synchronization or external limitation of growth by the carbon source.

Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20705-10. Epub 2008 Dec 19.
Determination of cell fate selection during phage lambda infection.
St-Pierre F, Endy D.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Abstract
Bacteriophage lambda infection of Escherichia coli can result in distinct cell fate outcomes. For example, some cells lyse whereas others survive as lysogens. A quantitative biophysical model of lambda infection supports the hypothesis that spontaneous differences in the timing of individual molecular events during lambda infection leads to variation in the selection of cell fates. Building from this analysis, the lambda lysis-lysogeny decision now serves as a paradigm for how intrinsic molecular noise can influence cellular behavior, drive developmental processes, and produce population heterogeneity. Here, we report experimental evidence that warrants reconsidering this framework. By using cell fractioning, plating, and single-cell fluorescent microscopy, we find that physical differences among cells present before infection bias lambda developmental outcomes. Specifically, variation in cell volume at the time of infection can be used to help predict cell fate: a approximately 2-fold increase in cell volume results in a 4- to 5-fold decrease in the probability of lysogeny. Other cell fate decisions now thought to be stochastic might also be determined by pre-existing variation.



Trends in Microbiology 

Volume 19, Issue 2,  Pages 49-104 (February 2011)








Opinion
Are low temperature habitats hot spots of microbial evolution driven by viruses?
Alexandre M. Anesioa,  and Christopher M. Bellasa
a Bristol Glaciology Centre, School of Geographical Sciences, University of Bristol, Bristol BS8 1SS, UK

Available online 3 December 2010. 

There is an increasing body of evidence to show that viruses are important drivers of microbial evolution and that they can store a great deal of the Earth's microbial diversity in their genomes. Examination of microbial diversity in polar regions has revealed a higher than expected diversity of viruses, bacteria and eukaryotic microbes. Further, the few available studies in polar regions reveal that viral control of microbial mortality is important in these habitats. In this opinion article, we argue that strong relationships between viruses and their hosts in a range of polar habitats could be key in explaining why polar regions are in fact hot spots of microbial diversity and evolution. Further, we argue that periodic glaciations, and particularly the Neoproterozoic low-latitude glaciation, known as ‘snowball Earth’, could have been periods of intense diversification in aquatic refuges.

Opinion
Time to recognise that mitochondria are bacteria?
Mark J. Pallena, 
a Centre for Systems Biology, School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK

Available online 1 December 2010. 

The scientific community is comfortable with recognising mitochondria as organelles that happen to be descendants of bacteria. Here, I playfully explore the arguments for and against a phylogenetic fundamentalism that states that mitochondria are bacteria and should be given their own taxonomic family, the Mitochondriaceae. I also explore the consequences of recognizing mitochondria as bacteria for our understanding of the systemic response to trauma and for the prospects of creating transgenic mitochondria.

 


Volume 41, Issue 3, 4 February 2011, Pages 247-248 


Article
Nascent Peptide in the Ribosome Exit Tunnel Affects Functional Properties of the A-Site of the Peptidyl Transferase Center
Haripriya Ramu1, Nora Vázquez-Laslop1, Dorota Klepacki1, Qing Dai2, Joseph Piccirilli3, Ronald Micura4 andAlexander S. Mankin1, , 
1 Center for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607, USA
2 Department of Molecular Genetics and Cell Biology, University of Illinois, Chicago, IL 60607, USA
3 Department of Biochemistry and Molecular Biology and Department of Chemistry, University of Chicago, Chicago, IL 60637, USA
4 Institute of Organic Chemistry and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria
Received 4 October 2010;  
revised 30 October 2010;  
accepted 11 November 2010.  
Published: February 3, 2011. 
Available online 3 February 2011. 


Referred to by:
Peptides in the Ribosomal Tunnel Talk Back
Molecular Cell, Volume 41, Issue 3, 4 February 2011, Pages 247-248, 
Daniel N. Wilson
 PDF (286 K)   |      
Summary
The ability to monitor the nascent peptide structure and to respond functionally to specific nascent peptide sequences is a fundamental property of the ribosome. An extreme manifestation of such response is nascent peptide-dependent ribosome stalling, involved in the regulation of gene expression. The molecular mechanisms of programmed translation arrest are unclear. By analyzing ribosome stalling at the regulatory cistron of the antibiotic resistance gene ermA, we uncovered a carefully orchestrated cooperation between the ribosomal exit tunnel and the A-site of the peptidyl transferase center (PTC) in halting translation. The presence of an inducing antibiotic and a specific nascent peptide in the exit tunnel abrogate the ability of the PTC to catalyze peptide bond formation with a particular subset of amino acids. The extent of the conferred A-site selectivity is modulated by the C-terminal segment of the nascent peptide, where the third-from-last residue plays a critical role.
Graphical Abstract
 

High-quality image (283K)

Highlights
► In the presence of erythromycin, the ribosome stalls at the 8th codon of ermAL1 ► Stalled ribosome is unable to catalyze peptide bond formation with the 9th amino acid ► The nature of the A-site codon is critical for stalling ► Nascent peptide sequence renders the A-site selective to the nature of aminoacyl-tRNA

Article
The Base-Pairing RNA Spot 42 Participates in a Multioutput Feedforward Loop to Help Enact Catabolite Repression inEscherichia coli
Chase L. Beisel1, ,  and Gisela Storz1, , 
1 Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892-5430, USA
Received 13 August 2010;  
revised 29 October 2010;  
accepted 1 December 2010.  
Published: February 3, 2011. 
Available online 3 February 2011. 


Referred to by:
Sweet Business: Spot42 RNA Networks with CRP to Modulate Catabolite Repression
Molecular Cell, Volume 41, Issue 3, 4 February 2011, Pages 245-246, 
Kai Papenfort, Jörg Vogel
 PDF (113 K)   |      
Summary
Bacteria selectively consume some carbon sources over others through a regulatory mechanism termed catabolite repression. Here, we show that the base-pairing RNA Spot 42 plays a broad role in catabolite repression in Escherichia coli by directly repressing genes involved in central and secondary metabolism, redox balancing, and the consumption of diverse nonpreferred carbon sources. Many of the genes repressed by Spot 42 are transcriptionally activated by the global regulator CRP. Since CRP represses Spot 42, these regulators participate in a specific regulatory circuit called a multioutput feedforward loop. We found that this loop can reduce leaky expression of target genes in the presence of glucose and can maintain repression of target genes under changing nutrient conditions. Our results suggest that base-pairing RNAs in feedforward loops can help shape the steady-state levels and dynamics of gene expression.
Graphical Abstract
 

High-quality image (256K)

Highlights
► Spot 42 regulates the consumption of numerous nonpreferred carbon sources ► Spot 42 participates with CRP in a multioutput coherent feedforward loop ► The loop can reduce the leaky expression of glucose-repressed genes ► The loop can help maintain glucose repression under changing nutrient conditions

Preview
Peptides in the Ribosomal Tunnel Talk Back
Daniel N. Wilson1, , 
1 Gene Center and Department for Biochemistry, Center for Protein Science-Munich (CiPS-M), University of Munich, Feodor-Lynen-Strasse 25, D-81377 Munich, Germany

Available online 3 February 2011. 


Refers to:
Nascent Peptide in the Ribosome Exit Tunnel Affects Functional Properties of the A-Site of the Peptidyl Transferase Center
Molecular Cell, Volume 41, Issue 3, 4 February 2011, Pages 321-330, 
Haripriya Ramu, Nora Vázquez-Laslop, Dorota Klepacki, Qing Dai, Joseph Piccirilli, Ronald Micura, Alexander S. Mankin
 PDF (868 K)   |  Supplementary content  |      
In this issue of Molecular Cell, Ramu et al. demonstrate that nascent peptides located within the ribosomal tunnel can talk back to the peptidyl transferase center to induce translational stalling by restricting the species of aminoacyl-tRNAs that can bind there.
Nascent Peptide in the Ribosome Exit Tunnel Affects Functional Properties of the A-Site of the Peptidyl Transferase Center  Original Research Article 

Pages 321-330 
Haripriya Ramu, Nora Vázquez-Laslop, Dorota Klepacki, Qing Dai, Joseph Piccirilli, Ronald Micura, Alexander S. Mankin
Graphical Abstract
Highlights
► In the presence of erythromycin, the ribosome stalls at the 8th codon of ermAL1 ► Stalled ribosome is unable to catalyze peptide bond formation with the 9th amino acid ► The nature of the A-site codon is critical for stalling ► Nascent peptide sequence renders the A-site selective to the nature of aminoacyl-tRNA

TABLE OF CONTENTS

February 2011 Volume 18, Issue 2
RNA secondary structure in mutually exclusive splicing pp159 - 168
Yun Yang, Leilei Zhan, Wenjing Zhang, Feng Sun, Wenfeng Wang, Nan Tian, Jingpei Bi, Haitao Wang, Dike Shi, Yajian Jiang, Yaozhou Zhang and Yongfeng Jin
doi:10.1038/nsmb.1959
Alternative splicing plays a major role in the generation of functional diversity but the underlying mechanisms remain poorly understood. In a comparative genome analysis of 73 arthropod species, spanning around 420 million years of evolution, Yongfeng and coworkers find built-in intronic elements that lead to mutual exclusive splicing. These elements are species- or clade-specific, but evolutionarily conserved at the secondary structure level.
Abstract | Full Text | PDF
Alternate rRNA secondary structures as regulators of translation pp169 - 176
Shu Feng, Heng Li, Jing Zhao, Konstantin Pervushin, Ky Lowenhaupt, Thomas U Schwartz and Peter Dröge
doi:10.1038/nsmb.1962
Understanding the structural dynamics of ribosomal components is key to understanding translation. The Z-DNA– and Z-RNA–binding domain from the human RNA editing enzyme ADAR1-L is now shown to bind to specific regions of ribosomal RNAs affecting translation, suggesting that these regions might at least transiently form Z-RNA structure not observed in crystal structures.
Abstract | Full Text | PDF
NATURE STRUCTURAL & MOLECULAR BIOLOGY | ARTICLE

Dynamic local unfolding in the serpin α-1 antitrypsin provides a mechanism for loop insertion and polymerization
Beena Krishnan	
& Lila M Gierasch
Affiliations
Contributions
Corresponding author
Nature Structural & Molecular Biology
 
18,
 
222–226
 
(2011)
 
doi:10.1038/nsmb.1976
Received
 
30 April 2010
 
Accepted
 
12 November 2010
 
Published online
 
23 January 2011
Abstract
Abstract
	
Accession codes
 
Author information
 
Supplementary information
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The conformational plasticity of serine protease inhibitors (serpins) underlies both their activities as protease inhibitors and their susceptibility to pathogenic misfolding and aggregation. Here, we structurally characterize a sheet-opened state of the serpin α-1 antitrypsin (α1AT) and show how local unfolding allows functionally essential strand insertion. Mutations in α1AT that cause polymerization-induced serpinopathies map to the labile region, suggesting that the evolution of serpin function required sampling of high risk conformations on a dynamic energy landscape.

Transcriptome-wide sequencing reveals numerous APOBEC1 mRNA-editing targets in transcript 3′ UTRs
Brad R Rosenberg,	
Claire E Hamilton,	
Michael M Mwangi,	
Scott Dewell	
& F Nina Papavasiliou
Affiliations
Contributions
Corresponding author
Nature Structural & Molecular Biology
 
18,
 
230–236
 
(2011)
 
doi:10.1038/nsmb.1975
Received
 
31 August 2010
 
Accepted
 
10 November 2010
 
Published online
 
23 January 2011
Abstract
Abstract
	
Accession codes
 
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Apolipoprotein B–editing enzyme, catalytic polypeptide-1 (APOBEC1) is a cytidine deaminase initially identified by its activity in converting a specific cytidine (C) to uridine (U) in apolipoprotein B (apoB) mRNA transcripts in the small intestine. Editing results in the translation of a truncated apoB isoform with distinct functions in lipid transport. To address the possibility that APOBEC1 edits additional mRNAs, we developed a transcriptome-wide comparative RNA sequencing (RNA-Seq) screen. We identified and validated 32 previously undescribed mRNA targets of APOBEC1 editing, all of which are located in AU-rich segments of transcript 3′ untranslated regions (3′ UTRs). Further analysis established several characteristic sequence features of editing targets, which were predictive for the identification of additional APOBEC1 substrates. The transcriptomics approach to RNA editing presented here dramatically expands the list of APOBEC1 mRNA editing targets and reveals a novel cellular mechanism for the modification of transcript 3′ UTRs.
Use of stable isotope labeling by amino acids in cell culture as a spike-in standard in quantitative proteomics
Tamar Geiger,	
Jacek R Wisniewski,	
Juergen Cox,	
Sara Zanivan,	
Marcus Kruger,	
Yasushi Ishihama	
&Matthias Mann
Affiliations
Contributions
Corresponding author
Nature Protocols
 
6,
 
147–157
 
(2011)
 
doi:10.1038/nprot.2010.192
Abstract
Abstract
	
Introduction
 
Materials
 
Procedure
 
Troubleshooting
 
Timing
 
Anticipated results
 
References
Acknowledgments
 
Author information
 
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Mass spectrometry (MS)-based proteomics is increasingly applied in a quantitative format, often based on labeling of samples with stable isotopes that are introduced chemically or metabolically. In the stable isotope labeling by amino acids in cell culture (SILAC) method, two cell populations are cultured in the presence of heavy or light amino acids (typically lysine and/or arginine), one of them is subjected to a perturbation, and then both are combined and processed together. In this study, we describe a different approach—the use of SILAC as an internal or 'spike-in' standard—wherein SILAC is only used to produce heavy labeled reference proteins or proteomes. These are added to the proteomes under investigation after cell lysis and before protein digestion. The actual experiment is therefore completely decoupled from the labeling procedure. Spike-in SILAC is very economical, robust and in principle applicable to all cell- or tissue-based proteomic analyses. Applications range from absolute quantification of single proteins to the quantification of whole proteomes. Spike-in SILAC is especially advantageous when analyzing the proteomes of whole tissues or organisms. The protocol describes the quantitative analysis of a tissue sample relative to super-SILAC spike-in, a mixture of five SILAC-labeled cell lines that accurately represents the tissue. It includes the selection and preparation of the spike-in SILAC standard, the sample preparation procedure, and analysis and evaluation of the results.

     
Article alert
The latest articles from BMC Genomics, published between 18-Jan-2011 and 31-Jan-2011
GC content around splice sites affects splicing through pre-mRNA secondary structures
Jing Zhang1 , CC Jay Kuo1  and Liang Chen2 
1 Ming Hsieh Department of Electrical Engineering, University of Southern California, Los Angeles, California 90089, USA
2 Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA
 author email corresponding author email
BMC Genomics 2011, 12:90doi:10.1186/1471-2164-12-90
Published:
31 January 2011
Abstract
Background
Alternative splicing increases protein diversity by generating multiple transcript isoforms from a single gene through different combinations of exons or through different selections of splice sites. It has been reported that RNA secondary structures are involved in alternative splicing. Here we perform a genomic study of RNA secondary structures around splice sites in humans (Homo sapiens), mice (Mus musculus), fruit flies (Drosophila melanogaster), and nematodes (Caenorhabditis elegans) to further investigate this phenomenon.
Results
We observe that GC content around splice sites is closely associated with the splice site usage in multiple species. RNA secondary structure is the possible explanation, because the structural stability difference among alternative splice sites, constitutive splice sites, and skipped splice sites can be explained by the GC content difference. Alternative splice sites tend to be GC-enriched and exhibit more stable RNA secondary structures in all of the considered species. In humans and mice, splice sites of first exons and long exons tend to be GC-enriched and hence form more stable structures, indicating the special role of RNA secondary structures in promoter proximal splicing events and the splicing of long exons. In addition, GC-enriched exon-intron junctions tend to be overrepresented in tissue-specific alternative splice sites, indicating the functional consequence of the GC effect. Compared with regions far from splice sites and decoy splice sites, real splice sites are GC-enriched. We also found that the GC-content effect is much stronger than the nucleotide-order effect to form stable secondary structures.
Conclusion
All of these results indicate that GC content is related to splice site usage and it may mediate the splicing process through RNA secondary structures.
Population transcriptomics of Drosophila melanogasterfemales
Lena Müller1 , Stephan Hutter1 , Rayna Stamboliyska1 , Sarah S Saminadin-Peter1,2 , Wolfgang Stephan1  and John Parsch1 
1 Department of Biology II, University of Munich (LMU), 82152 Planegg-Martinsried, Germany
2 Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
 author email corresponding author email
BMC Genomics 2011, 12:81doi:10.1186/1471-2164-12-81
Published:
28 January 2011
Abstract
Background
Variation at the level of gene expression is abundant in natural populations and is thought to contribute to the adaptive divergence of populations and species. Gene expression also differs considerably between males and females. Here we report a microarray analysis of gene expression variation among females of 16 Drosophilamelanogaster strains derived from natural populations, including eight strains from the putative ancestral range in sub-Saharan Africa and eight strains from Europe. Gene expression variation among males of the same strains was reported previously.
Results
We detected relatively low levels of expression polymorphism within populations, but much higher expression divergence between populations. A total of 569 genes showed a significant expression difference between the African and European populations at a false discovery rate of 5%. Genes with significant over-expression in Europe included the insecticide resistance gene Cyp6g1, as well as genes involved in proteolysis and olfaction. Genes with functions in carbohydrate metabolism and vision were significantly over-expressed in the African population. There was little overlap between genes expressed differently between populations in females and males.
Conclusions
Our results suggest that adaptive changes in gene expression have accompanied the out-of-Africa migration of D. melanogaster. Comparison of female and male expression data indicates that the vast majority of genes differing in expression between populations do so in only one sex and suggests that most regulatory adaptation has been sex-specific.
Conserved generation of short products at piRNA loci
Philipp Berninger1,2 , Lukasz Jaskiewicz1 , Mohsen Khorshid1  and Mihaela Zavolan1 
1 Biozentrum, Universität Basel and Swiss Institute of Bioinformatics, Klingelbergstrasse 50-70, 4056 Basel, Switzerland
2 EMBL Grenoble, 6 rue Jules Horowitz, 38042 Grenoble, France
 author email corresponding author email
BMC Genomics 2011, 12:46doi:10.1186/1471-2164-12-46
Published:
19 January 2011
Abstract
Background
The piRNA pathway operates in animal germ lines to ensure genome integrity through retrotransposon silencing. The Piwi protein-associated small RNAs (piRNAs) guide Piwi proteins to retrotransposon transcripts, which are degraded and thereby post-transcriptionally silenced through a ping-pong amplification process. Cleavage of the retrotransposon transcript defines at the same time the 5' end of a secondary piRNA that will in turn guide a Piwi protein to a primary piRNA precursor, thereby amplifying primary piRNAs. Although several studies provided evidence that this mechanism is conserved among metazoa, how the process is initiated and what enzymatic activities are responsible for generating the primary and secondary piRNAs are not entirely clear.
Results
Here we analyzed small RNAs from three mammalian species, seeking to gain further insight into the mechanisms responsible for the piRNA amplification loop. We found that in all these species piRNA-directed targeting is accompanied by the generation of short sequences that have a very precisely defined length, 19 nucleotides, and a specific spatial relationship with the guide piRNAs.
Conclusions
This suggests that the processing of the 5' product of piRNA-guided cleavage occurs while the piRNA target is engaged by the Piwi protein. Although they are not stabilized through methylation of their 3' ends, the 19-mers are abundant not only in testes lysates but also in immunoprecipitates of Miwi and Mili proteins. They will enable more accurate identification of piRNA loci in deep sequencing data sets.
     
Article alert
The latest articles from BMC Systems Biology, published between 18-Jan-2011 and 31-Jan-2011
Noise regulation by quorum sensing in low mRNA copy number systems
Marc Weber  and Javier Buceta 
Computer Simulation and Modelling (Co.S.Mo.) Lab, Parc Científic de Barcelona, C/Baldiri Reixac 10-12, Barcelona 08028, Spain
 author email corresponding author email
BMC Systems Biology 2011, 5:11doi:10.1186/1752-0509-5-11
Published:
20 January 2011
Abstract
Background
Cells must face the ubiquitous presence of noise at the level of signaling molecules. The latter constitutes a major challenge for the regulation of cellular functions including communication processes. In the context of prokaryotic communication, the so-called quorum sensing (QS) mechanism relies on small diffusive molecules that are produced and detected by cells. This poses the intriguing question of how bacteria cope with the fluctuations for setting up a reliable information exchange.
Results
We present a stochastic model of gene expression that accounts for the main biochemical processes that describe the QS mechanism close to its activation threshold. Within that framework we study, both numerically and analytically, the role that diffusion plays in the regulation of the dynamics and the fluctuations of signaling molecules. In addition, we unveil the contribution of different sources of noise, intrinsic and transcriptional, in the QS mechanism.
Conclusions
The interplay between noisy sources and the communication process produces a repertoire of dynamics that depends on the diffusion rate. Importantly, the total noise shows a non-monotonic behavior as a function of the diffusion rate. QS systems seems to avoid values of the diffusion that maximize the total noise. These results point towards the direction that bacteria have adapted their communication mechanisms in order to improve the signal-to-noise ratio.


[About the cover]
Science, 11 February 2011 (Volume 331, Issue 6018) 
http://www.sciencemag.org/content/vol331/issue6018/index.dtl?etoc
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