An enhancer trap line identifies the Drosophila homolog of the L37a ribosomal protein

A gene identified from an enhancer trap screen is shown to encode the Drosophila melanogaster homolog of the L37a ribosomal protein. The predicted 92 amino-acid sequence of this protein is 78% identical to mammalian L37a proteins, and contains a conserved Cys-X2 Cys-X14-Cys-X2-Cys zinc finger motif that may be involved in interactions with ribosomal RNA. The Drosophila L37a homolog is a single copy gene comprised of four exons and is ubiquitously expressed throughout the animal. Cytological localization reveals that Drosophila L37a maps to position 25C1-3, very near the previously described Minute mutation M(2)25C.     

The human homolog of Sex comb on midleg (SCMH1) maps to chromosome 1p34.

Polycomb group genes were originally identified in Drosophila as repressors required to maintain the silenced state of homeotic loci. About ten Polycomb group genes have been cloned in Drosophila, and mammalian homologs have been identified for most of these. Here, we isolate cDNAs encoding two isoforms of a human homolog of Drosophila Sex comb on midleg (Scm), named Sex comb on midleg homolog-1 (SCMH1). Overall, SCMH1 has 94% identity to its mouse counterpart Scmh1, and 41% identity to Scm, and contains two 1(3)mbt domains, and the SPM domain that are characteristic of Scm. SCMH1 is widely expressed in adult tissues, and maps to chromosome 1p34.     

A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21

A novel paternally expressed imprinted gene, PEG10 (Paternally Expressed 10), was identified on human chromosome 7q21. PEG10 is located near the SGCE (Sarcoglycan epsilon) gene, whose mouse homologue was recently shown to be imprinted. Therefore, it is highly possible that a new imprinted gene cluster exists on human chromosome 7q21. Analysis of two predicted open reading frames (ORF1 and ORF2) revealed that ORF1 and ORF2 have homology to the gag and pol proteins of some vertebrate retrotransposons, respectively. These data suggest that PEG10 is derived from a retrotransposon that was previously integrated into the mammalian genome. PEG10 is likely to be essential for understanding how exogenous genes become imprinted.     

Cloning, chromosomal organization and expression analysis of Neurl, the mouse homolog of Drosophila melanogaster neuralized gene

The Drosophila neuralized (neur) gene belongs to the neurogenic group of genes involved in regulating cell-cell interactions required for neural precursor development. neur mutant phenotypes include strong overcommitment to neural fates at the expense of epidermal fates. The human neuralized homolog (NEURL) has been recently determined and found to map to chromosome 10q25.1 within the region frequently deleted in malignant astrocytomas. Because of its potential importance in developmental processes, we analyzed the structure of the mouse homolog, Neurl, and its expression pattern in embryonic tissues. Neurl activity is detected from early developmental stages in several tissues and organs including neural tissues, limbs, the skeletal system, sense organs and internal organs undergoing epithelial-mesenchymal interactions. Neurl encodes a polypeptide associated with the plasma membrane but also detected in the cytoplasm. Similarly to the Drosophila gene, mammalian neuralized may code for an important regulatory factor.     

Isolation and characterization of a mammalian homolog of the Drosophila white gene

The Drosophila melanogaster white gene is a member of the ABC transporter superfamily of ATPase transmembrane proteins and is involved in the cellular uptake of guanine and tryptophan. We have cloned and sequenced human and mouse homologs of white which share 55–58% amino acid similarity with the Drosophila protein. Northern analysis reveals that the mammalian homolog is highly expressed in several tissues, including brain, spleen, lung and placenta. We have localized the gene to human chromosome 21q22.3 by means of fluorescence in situ hybridization and linkage analysis using a (CA)_n polymorphism. The human homolog maps to the interval between D21S212 and D21S171, a region which includes loci for bipolar affective disorder and a recessive form of deafness. Since tryptophan is a precursor for the neurotransmitter serotonin and neurotoxic metabolites of the kynurenine pathway, we propose that the human homolog of white is a suitable candidate gene for these neurological disorders in humans.     

Expression specificity of the mouse exonuclease 1 (mExo1) gene.

Genetic recombination involves either the homo-logous exchange of nearly identical chromosome regions or the direct alignment, annealing and ligation of processed DNA ends. These mechanisms are involved in repairing potentially lethal or mutagenic DNA damage and generating genetic diversity within the meiotic cell population and antibody repertoire. We report here the identification of a mouse gene, termed mExo1 for mouse exonuclease 1, which encodes a approximately 92 kDa protein that shares homology to proteins of the RAD2 nuclease family, most notably human 5' to 3' exonuclease Hex1/hExo1, yeast exonuclease 1 (Exo1) proteins and Drosophila melanogaster Tosca. The mExo1 gene maps to distal chromosome 1, consistent with the recent mapping of the orthologous HEX1 / hEXO1 gene to chromosome 1q42-q43. mExo1 is expressed prominently in testis, an area of active homologous recombination, and spleen, a prominent lymphoid tissue. An increased level of mExo1 mRNA was observed during a stage of testis development where cells that are actively involved in meiotic recombination arise first and represent a significant proportion of the germ cell population. Comparative evaluation of the expression patterns of the human and mouse genes, combined with previous biochemical and yeast genetic studies, indicate that the Exo1-like proteins are important contributors to chromosome processing during mammalian DNA repair and recombination.     

A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase.

Antibodies to the human Shc adaptor protein were used to isolate a cDNA encoding a Drosophila Shc protein (dShc) by screening an expression library. The dshc gene, which maps to position 67B-C on the third chromosome, encodes a 45-kDa protein that is widely expressed throughout the Drosophila life cycle. In flies, the dShc protein physically associates with the activated Drosophila epidermal growth factor receptor homolog (DER) and is inducibly phosphorylated on tyrosine by DER. The 45-kDa dShc protein is closely related both in overall organization and in amino acid sequence (46% identity) to the 52-kDa mammalian Shc isoform. In addition to a C-terminal Src homology 2 (SH2) domain, dShc contains an N-terminal phosphotyrosine-binding (PTB) domain, which associates in vitro with the autophosphorylated DER receptor tyrosine kinase and with phosphopeptides containing an Asn-Pro-X-pTyr motif, where pTyr stands for phosphotyrosine. A potential binding site for the dShc PTB domain is located at Tyr-1228 of DER. These results indicate that the shc gene has been conserved in evolution, as have the binding properties of the Shc PTB and SH2 domains. Despite the close relationship between the Drosophila and mammalian Shc proteins, dShc lacks the high-affinity Grb2-binding site found in mammalian Shc, suggesting that Shc proteins may have functions in addition to regulation of the Ras pathway.