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861.
862.
Genome-wide atlas of gene expression in the adult mouse brain 总被引:1,自引:0,他引:1
Lein ES Hawrylycz MJ Ao N Ayres M Bensinger A Bernard A Boe AF Boguski MS Brockway KS Byrnes EJ Chen L Chen L Chen TM Chin MC Chong J Crook BE Czaplinska A Dang CN Datta S Dee NR Desaki AL Desta T Diep E Dolbeare TA Donelan MJ Dong HW Dougherty JG Duncan BJ Ebbert AJ Eichele G Estin LK Faber C Facer BA Fields R Fischer SR Fliss TP Frensley C Gates SN Glattfelder KJ Halverson KR Hart MR Hohmann JG Howell MP Jeung DP Johnson RA Karr PT Kawal R Kidney JM Knapik RH Kuan CL Lake JH Laramee AR 《Nature》2007,445(7124):168-176
Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function. 相似文献
863.
Accounting for the abundance of genetic variation in the face of natural selection remains a central problem of evolutionary biology. Genetic polymorphisms are constantly arising through mutation, and although most are promptly eliminated, polymorphisms in functionally important traits are common. One mechanism that can maintain polymorphisms is negative frequency-dependent selection on alternative alleles, whereby the fitness of each decreases as its frequency increases. Examples of frequency-dependent selection are rare, especially when attempting to describe the genetic basis of the phenotype under selection. Here we show frequency-dependent selection in a well-known natural genetic polymorphism affecting fruitfly foraging behaviour. When raised in low nutrient conditions, both of the naturally occurring alleles of the foraging gene (for(s) and for(R)) have their highest fitness when rare-the hallmark of negative frequency-dependent selection. This effect disappears at higher resources levels, demonstrating the role of larval competition. We are able to confirm the involvement of the foraging gene by showing that a sitter-like mutant allele on a rover background has similar frequency-dependent fitness as the natural sitter allele. Our study represents a clear demonstration of frequency-dependent selection, and we are able to attribute this effect to a single, naturally polymorphic gene known to affect behaviour. 相似文献
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865.
Here we discuss recent advances surrounding the origin of angiosperms. Putatively primitive characters are now much better understood because of a vastly improved understanding of angiosperm phylogenetics, and recent discoveries of fossil flowers have provided an increasingly detailed picture of early diversity in the angiosperms. The 'anthophyte theory', the dominant concept of the 1980s and 1990s, has been eclipsed; Gnetales, previously thought to be closest to the angiosperms, are related instead to other extant gymnosperms, probably most closely to conifers. Finally, new theories of flower origins have been proposed based on gene function, duplication and loss, as well as on morphology. Further studies of genetic mechanisms that control reproductive development in seed plants provide a most promising avenue for further research, including tests of these recent theories. Identification of fossils with morphologies that convincingly place them close to angiosperms could still revolutionize understanding of angiosperm origins. 相似文献
866.
Henzler-Wildman KA Thai V Lei M Ott M Wolf-Watz M Fenn T Pozharski E Wilson MA Petsko GA Karplus M Hübner CG Kern D 《Nature》2007,450(7171):838-844
The mechanisms by which enzymes achieve extraordinary rate acceleration and specificity have long been of key interest in biochemistry. It is generally recognized that substrate binding coupled to conformational changes of the substrate-enzyme complex aligns the reactive groups in an optimal environment for efficient chemistry. Although chemical mechanisms have been elucidated for many enzymes, the question of how enzymes achieve the catalytically competent state has only recently become approachable by experiment and computation. Here we show crystallographic evidence for conformational substates along the trajectory towards the catalytically competent 'closed' state in the ligand-free form of the enzyme adenylate kinase. Molecular dynamics simulations indicate that these partially closed conformations are sampled in nanoseconds, whereas nuclear magnetic resonance and single-molecule fluorescence resonance energy transfer reveal rare sampling of a fully closed conformation occurring on the microsecond-to-millisecond timescale. Thus, the larger-scale motions in substrate-free adenylate kinase are not random, but preferentially follow the pathways that create the configuration capable of proficient chemistry. Such preferred directionality, encoded in the fold, may contribute to catalysis in many enzymes. 相似文献
867.
Tomlins SA Laxman B Dhanasekaran SM Helgeson BE Cao X Morris DS Menon A Jing X Cao Q Han B Yu J Wang L Montie JE Rubin MA Pienta KJ Roulston D Shah RB Varambally S Mehra R Chinnaiyan AM 《Nature》2007,448(7153):595-599
Recently, we identified recurrent gene fusions involving the 5' untranslated region of the androgen-regulated gene TMPRSS2 and the ETS (E26 transformation-specific) family genes ERG, ETV1 or ETV4 in most prostate cancers. Whereas TMPRSS2-ERG fusions are predominant, fewer TMPRSS2-ETV1 cases have been identified than expected on the basis of the frequency of high (outlier) expression of ETV1 (refs 3-13). Here we explore the mechanism of ETV1 outlier expression in human prostate tumours and prostate cancer cell lines. We identified previously unknown 5' fusion partners in prostate tumours with ETV1 outlier expression, including untranslated regions from a prostate-specific androgen-induced gene (SLC45A3) and an endogenous retroviral element (HERV-K_22q11.23), a prostate-specific androgen-repressed gene (C15orf21), and a strongly expressed housekeeping gene (HNRPA2B1). To study aberrant activation of ETV1, we identified two prostate cancer cell lines, LNCaP and MDA-PCa 2B, that had ETV1 outlier expression. Through distinct mechanisms, the entire ETV1 locus (7p21) is rearranged to a 1.5-megabase prostate-specific region at 14q13.3-14q21.1 in both LNCaP cells (cryptic insertion) and MDA-PCa 2B cells (balanced translocation). Because the common factor of these rearrangements is aberrant ETV1 overexpression, we recapitulated this event in vitro and in vivo, demonstrating that ETV1 overexpression in benign prostate cells and in the mouse prostate confers neoplastic phenotypes. Identification of distinct classes of ETS gene rearrangements demonstrates that dormant oncogenes can be activated in prostate cancer by juxtaposition to tissue-specific or ubiquitously active genomic loci. Subversion of active genomic regulatory elements may serve as a more generalized mechanism for carcinoma development. Furthermore, the identification of androgen-repressed and insensitive 5' fusion partners may have implications for the anti-androgen treatment of advanced prostate cancer. 相似文献
868.
869.
Weir BA Woo MS Getz G Perner S Ding L Beroukhim R Lin WM Province MA Kraja A Johnson LA Shah K Sato M Thomas RK Barletta JA Borecki IB Broderick S Chang AC Chiang DY Chirieac LR Cho J Fujii Y Gazdar AF Giordano T Greulich H Hanna M Johnson BE Kris MG Lash A Lin L Lindeman N Mardis ER McPherson JD Minna JD Morgan MB Nadel M Orringer MB Osborne JR Ozenberger B Ramos AH Robinson J Roth JA Rusch V Sasaki H Shepherd F Sougnez C Spitz MR Tsao MS Twomey D Verhaak RG Weinstock GM Wheeler DA Winckler W 《Nature》2007,450(7171):893-898
870.