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M Ashburner

Publications and source records attributed to M Ashburner.

At least 19 recordsLinked to original sources
PubMed2001

Functional annotation of a full-length mouse cDNA collection.

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Animals↗
PubMed2000

The genome sequence of Drosophila melanogaster.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Animals↗
PubMed2000

Comparative genomics of the eukaryotes.

A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.

Animals↗
PubMed2000

From sequence to chromosome: the tip of the X chromosome of D. melanogaster.

One of the rewards of having a Drosophila melanogaster whole-genome sequence will be the potential to understand the molecular bases for structural features of chromosomes that have been a long-standing puzzle. Analysis of 2.6 megabases of sequence from the tip of the X chromosome of Drosophila identifies 273 genes. Cloned DNAs from the characteristic bulbous structure at the tip of the X chromosome in the region of the broad complex display an unusual pattern of in situ hybridization. Sequence analysis revealed that this region comprises 154 kilobases of DNA flanked by 1.2-kilobases of inverted repeats, each composed of a 350-base pair satellite related element. Thus, some aspects of chromosome structure appear to be revealed directly within the DNA sequence itself.

Animals↗
PubMed2000

Sequence variation database project at the European Bioinformatics Institute.

The sequence variation project at EBI aims to create a unified resource for browsing and searching sequence differences. Technical advances in reading in new data types and in validating and cross-referencing entries are reported. It is suggested that the hardest problems in unifying mutation databases are related to intellectual property rights. The concept of copylefting is introduced as a potential solution to these.

Computational Biology↗
PubMed2000

Annotating eukaryote genomes.

The Genome Annotation Assessment Project tested current methods of gene identification, including a critical assessment of the accuracy of different methods. Two new databases have provided new resources for gene annotation: these are the InterPro database of protein domains and motifs, and the Gene Ontology database for terms that describe the molecular functions and biological roles of gene products. Efforts in genome annotation are most often based upon advances in computer systems that are specifically designed to deal with the tremendous amounts of data being generated by current sequencing projects. These efforts in analysis are being linked to new ways of visualizing computationally annotated genomes.

Animals↗
PubMed2000

Molecular organization of the Drosophila melanogaster Adh chromosomal region in D. repleta and D. buzzatii, two distantly related species of the Drosophila subgenus.

The molecular organization of a 1.944-Mb chromosomal region of Drosophila melanogaster around the Adh locus has been analyzed in two repleta group species: D. repleta and D. buzzatii. The extensive genetic and molecular information about this region in D. melanogaster makes it a prime choice for comparative studies of genomic organization among distantly related species. A set of 26 P1 phages from D. melanogaster were successfully hybridized using fluorescence in-situ hybridization (FISH) to the salivary gland chromosomes of both repleta group species. The results show that the Adh region is distributed in D. repleta and D. buzatii over six distant sites of chromosome 3, homologous to chromosomal arm 2L of D. melanogaster (Muller's element B). This observation implies a density of 2.57 fixed breakpoints per Mb in the Adh region and suggests a considerable reorganization of this chromosomal element via the fixation of paracentric inversions. Nevertheless, breakpoint density in the Adh region is three times lower than that estimated for D. repleta chromosome 2, homologous to D. melanogaster 3R (Muller's element E). Differences in the rate of evolution among chromosomal elements are seemingly persistent in the Drosophila genus over long phylogenetic distances.

Animals↗
PubMed2000

The Drosophila melanogaster hybrid male rescue gene causes inviability in male and female species hybrids.

The Drosophila melanogaster mutation Hmr rescues inviable hybrid sons from the cross of D. melanogaster females to males of its sibling species D. mauritiana, D. simulans, and D. sechellia. We have extended previous observations that hybrid daughters from this cross are poorly viable at high temperatures and have shown that this female lethality is suppressed by Hmr and the rescue mutations In(1)AB and D. simulans Lhr. Deficiencies defined here as Hmr(-) also suppressed lethality, demonstrating that reducing Hmr(+) activity can rescue otherwise inviable hybrids. An Hmr(+) duplication had the opposite effect of reducing the viability of female and sibling X-male hybrid progeny. Similar dose-dependent viability effects of Hmr were observed in the reciprocal cross of D. simulans females to D. melanogaster males. Finally, Lhr and Hmr(+) were shown to have mutually antagonistic effects on hybrid viability. These data suggest a model where the interaction of sibling species Lhr(+) and D. melanogaster Hmr(+) causes lethality in both sexes of species hybrids and in both directions of crossing. Our results further suggest that a twofold difference in Hmr(+) dosage accounts in part for the differential viability of male and female hybrid progeny, but also that additional, unidentified genes must be invoked to account for the invariant lethality of hybrid sons of D. melanogaster mothers. Implications of our findings for understanding Haldane's rule-the observation that hybrid breakdown is often specific to the heterogametic sex-are also discussed.

Animals↗
PubMed2000

The Drosophila embargoed gene is required for larval progression and encodes the functional homolog of schizosaccharomyces Crm1.

The CRM1 (Exportin 1) protein is a receptor for leucine-rich nuclear export signal sequences. We have molecularly characterized the Drosophila melanogaster embargoed (emb) gene and find that it encodes a product with 49 and 71% sequence identity to the fission yeast Schizosaccharomyces pombe and human CRM1 proteins, respectively. We show that expression of the emb cDNA is sufficient to suppress the growth phenotype of both conditional-lethal and null S. pombe crm1(-) mutant strains, suggesting that emb encodes the functional homologue of the S. pombe Crm1 protein. Through mutagenesis screens we have recovered a series of recessive lethal emb mutations. There is a substantial maternal contribution of emb mRNA and animals hemizygous for our emb alleles can develop to second instar larvae but persist at this stage and consistently fail to undergo the molt to the third instar stage. We see a nuclear accumulation of endogenous actin in the intestinal epithelial cells of the emb mutant larvae, consistent with a role for the emb gene product in nuclear export of actin protein.

Actins↗
PubMed2000

Duplication, dicistronic transcription, and subsequent evolution of the Alcohol dehydrogenase and Alcohol dehydrogenase-related genes in Drosophila.

It has recently been discovered that the Alcohol dehydrogenase and Alcohol dehydrogenase-related genes of Drosophila melanogaster and closely related species constitute a single transcription unit and that the Alcohol dehydrogenase-related gene is exclusively expressed from a dicistronic mRNA. Here, we show that in Drosophila lebanonensis, subgenus Scaptodrosophila, Adhr: is also transcribed as a dicistronic transcript with Adh Using degenerate primers designed on the sequence of the known Adhr proteins, we have been able to amplify and sequence a partial sequence of Adhr: in species representative of the whole subgenus Drosophila. This has allowed the study of the organization and expression of Adhr: in Drosophila buzzatii. We find that in D. buzzatii Adhr is transcribed as a monocistronic transcript. Adh and Adhr are believed to originate by duplication, and our data suggest that the cotranscription of these two genes was the primitive state, and that their independent transcription in the subgenus Drosophila is derived. We can rationalize the D. buzzatii condition as being correlated with the two genes evolving independent transcriptional control. However, why these two genes with clear divergence in the functions of their proteins should remain cotranscribed in groups as divergent as the subgenus Sophophora and the subgenus Scaptodrosophila remains a mystery.

Alcohol Dehydrogenase↗
PubMed1999

Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila.

The antifungal defense of Drosophila is controlled by the spaetzle/Toll/cactus gene cassette. Here, a loss-of-function mutation in the gene encoding a blood serine protease inhibitor, Spn43Ac, was shown to lead to constitutive expression of the antifungal peptide drosomycin, and this effect was mediated by the spaetzle and Toll gene products. Spaetzle was cleaved by proteolytic enzymes to its active ligand form shortly after immune challenge, and cleaved Spaetzle was constitutively present in Spn43Ac-deficient flies. Hence, Spn43Ac negatively regulates the Toll signaling pathway, and Toll does not function as a pattern recognition receptor in the Drosophila host defense.

Animals↗
PubMed1999

An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region.

A contiguous sequence of nearly 3 Mb from the genome of Drosophila melanogaster has been sequenced from a series of overlapping P1 and BAC clones. This region covers 69 chromosome polytene bands on chromosome arm 2L, including the genetically well-characterized "Adh region." A computational analysis of the sequence predicts 218 protein-coding genes, 11 tRNAs, and 17 transposable element sequences. At least 38 of the protein-coding genes are arranged in clusters of from 2 to 6 closely related genes, suggesting extensive tandem duplication. The gene density is one protein-coding gene every 13 kb; the transposable element density is one element every 171 kb. Of 73 genes in this region identified by genetic analysis, 49 have been located on the sequence; P-element insertions have been mapped to 43 genes. Ninety-five (44%) of the known and predicted genes match a Drosophila EST, and 144 (66%) have clear similarities to proteins in other organisms. Genes known to have mutant phenotypes are more likely to be represented in cDNA libraries, and far more likely to have products similar to proteins of other organisms, than are genes with no known mutant phenotype. Over 650 chromosome aberration breakpoints map to this chromosome region, and their nonrandom distribution on the genetic map reflects variation in gene spacing on the DNA. This is the first large-scale analysis of the genome of D. melanogaster at the sequence level. In addition to the direct results obtained, this analysis has allowed us to develop and test methods that will be needed to interpret the complete sequence of the genome of this species. Before beginning a Hunt, it is wise to ask someone what you are looking for before you begin looking for it. Milne 1926

Alcohol Dehydrogenase↗
PubMed1999

stress sensitive B encodes an adenine nucleotide translocase in Drosophila melanogaster.

Adenine nucleotide translocases (ANT) are required for the exchange of ADP and ATP across the inner mitochondrial membrane. They are essential for life, and most eukaryotes have at least two different Ant genes. Only one gene had been described from Drosophila, and this had not been characterized genetically. We show that mutations in this gene correspond to the previously described loci, sesB and l(1)9Ed. Immediately adjacent to this gene is another encoding a second ANT protein, which has 78% identity to that encoded by sesB/l(1)9Ed. These two genes are transcribed from a common promoter, and their mRNAs are produced by differential splicing. Hutter and Karch suggested that the sesB ANT gene corresponded to Hmr, a gene identified by an allele that rescues otherwise inviable interspecific hybrids between Drosophila melanogaster and its sibling species. This hypothesis is not supported by our study of the ANT genes of D. melanogaster.

Amino Acid Sequence↗
PubMed1999

[Comparison of the molecular and genetic map of the 2B6-2B7-8 of Drosophila melanogaster X-chromosome].

Molecular and genetic data were compared for the 2B6-2B7-8 region of the Drosophila melanogaster X chromosome. This region contains the dor (deep orange) and swi (single wing) genes influencing ecdysterone-dependent gene expression. Genes which had not been identified previously by genetic methods were shown to be present in this region. Two novel loci, designated a6 and b6, were characterized in detail. Both genes are expressed throughout Drosophila embryogenesis. The product of b6 has a homology with mammalian pentraxins. This is the first Drosophila gene found to contain the pentraxin motif.

Amino Acid Sequence↗