RESUMO
Mechanoreceptors are sensory cells that transduce mechanical stimuli into electrical signals and mediate the perception of sound, touch and acceleration. Ciliated mechanoreceptors possess an elaborate microtubule cytoskeleton that facilitates the coupling of external forces to the transduction apparatus. In a screen for genes preferentially expressed in Drosophila campaniform mechanoreceptors, we identified DCX-EMAP, a unique member of the EMAP family (echinoderm-microtubule-associated proteins) that contains two doublecortin domains. DCX-EMAP localizes to the tubular body in campaniform receptors and to the ciliary dilation in chordotonal mechanoreceptors in Johnston's organ, the fly's auditory organ. Adult flies carrying a piggyBac insertion in the DCX-EMAP gene are uncoordinated and deaf and display loss of mechanosensory transduction and amplification. Electron microscopy of mutant sensilla reveals loss of electron-dense materials within the microtubule cytoskeleton in the tubular body and ciliary dilation. Our results establish a catalogue of candidate genes for Drosophila mechanosensation and show that one candidate, DCX-EMAP, is likely to be required for mechanosensory transduction and amplification.
Assuntos
Cílios/metabolismo , Drosophila/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Animais , Linhagem Celular Tumoral , Cílios/genética , Cílios/ultraestrutura , Drosophila/genética , Drosophila/ultraestrutura , Humanos , Mecanotransdução Celular/genética , Mecanotransdução Celular/fisiologia , Microscopia Eletrônica de Transmissão , Proteínas Associadas aos Microtúbulos/classificação , Proteínas Associadas aos Microtúbulos/genética , Filogenia , Células Receptoras Sensoriais/metabolismoRESUMO
Changes in gene expression play an important role in species' evolution. Earlier studies uncovered evidence that the effect of mutations on expression levels within the primate order is skewed, with many small downregulations balanced by fewer but larger upregulations. In addition, brain-expressed genes appeared to show an increased rate of evolution on the branch leading to human. However, the lack of a mathematical model adequately describing the evolution of gene expression precluded the rigorous establishment of these observations. Here, we develop mathematical tools that allow us to revisit these earlier observations in a model-testing and inference framework. We introduce a model for skewed gene-expression evolution within a phylogenetic tree and use a separate model to account for biological or experimental outliers. A Bayesian Markov chain Monte Carlo inference procedure allows us to infer the phylogeny and other evolutionary parameters, while quantifying the confidence in these inferences. Our results support previous observations; in particular, we find strong evidence for a sustained positive skew in the distribution of gene-expression changes in primate evolution. We propose a "corrective sweep" scenario to explain this phenomenon.
Assuntos
Encéfalo/fisiologia , Evolução Molecular , Expressão Gênica , Modelos Biológicos , Modelos Estatísticos , Primatas/genética , Animais , Simulação por Computador , Perfilação da Expressão Gênica , Genoma , Humanos , Método de Monte Carlo , Filogenia , Especificidade da EspécieRESUMO
The global amino acid compositions as deduced from the complete genomic sequences of six thermophilic archaea, two thermophilic bacteria, 17 mesophilic bacteria and two eukaryotic species were analysed by hierarchical clustering and principal components analysis. Both methods showed an influence of several factors on amino acid composition. Although GC content has a dominant effect, thermophilic species can be identified by their global amino acid compositions alone. This study presents a careful statistical analysis of factors that affect amino acid composition and also yielded specific features of the average amino acid composition of thermophilic species. Moreover, we introduce the first example of a 'compositional tree' of species that takes into account not only homologous proteins, but also proteins unique to particular species. We expect this simple yet novel approach to be a useful additional tool for the study of phylogeny at the genome level.
Assuntos
Aminoácidos/genética , Genoma , Aminoácidos/química , Animais , Archaea/genética , Bactérias/genética , Caenorhabditis elegans/genética , Bases de Dados Factuais , Genoma Arqueal , Genoma Bacteriano , Genoma Fúngico , Filogenia , Saccharomyces cerevisiae/genética , Especificidade da Espécie , TemperaturaRESUMO
MOTIVATION: Sensitive detection and masking of low-complexity regions in protein sequences. Filtered sequences can be used in sequence comparison without the risk of matching compositionally biased regions. The main advantage of the method over similar approaches is the selective masking of single residue types without affecting other, possibly important, regions. RESULTS: A novel algorithm for low-complexity region detection and selective masking. The algorithm is based on multiple-pass Smith-Waterman comparison of the query sequence against twenty homopolymers with infinite gap penalties. The output of the algorithm is both the masked query sequence for further analysis, e.g. database searches, as well as the regions of low complexity. The detection of low-complexity regions is highly specific for single residue types. It is shown that this approach is sufficient for masking database query sequences without generating false positives. The algorithm is benchmarked against widely available algorithms using the 210 genes of Plasmodium falciparum chromosome 2, a dataset known to contain a large number of low-complexity regions. AVAILABILITY: CAST (version 1.0) executable binaries are available to academic users free of charge under license. Web site entry point, server and additional material: http://www.ebi.ac.uk/research/cgg/services/cast/
