Publications (17)108.41 Total impact
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Article: The Drosophila melanogaster hybrid male rescue gene causes inviability in male and female species hybrids.
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ABSTRACT: 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.Genetics 05/2000; 154(4):1747-71. · 4.01 Impact Factor -
Article: The tamas gene, identified as a mutation that disrupts larval behavior in Drosophila melanogaster, codes for the mitochondrial DNA polymerase catalytic subunit (DNApol-gamma125).
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ABSTRACT: From a screen of pupal lethal lines of Drosophila melanogaster we identified a mutant strain that displayed a reproducible reduction in the larval response to light. Moreover, this mutant strain showed defects in the development of the adult visual system and failure to undergo behavioral changes characteristic of the wandering stage. The foraging third instar larvae remained in the food substrate for a prolonged period and died at or just before pupariation. Using a new assay for individual larval photobehavior we determined that the lack of response to light in these mutants was due to a primary deficit in locomotion. The mutation responsible for these phenotypes was mapped to the lethal complementation group l(2)34Dc, which we renamed tamas (translated from Sanskrit as "dark inertia"). Sequencing of mutant alleles demonstrated that tamas codes for the mitochondrial DNA polymerase catalytic subunit (DNApol-gamma125).Genetics 01/2000; 153(4):1809-24. · 4.01 Impact Factor -
Article: stress sensitive B encodes an adenine nucleotide translocase in Drosophila melanogaster.
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ABSTRACT: 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.Genetics 11/1999; 153(2):891-903. · 4.01 Impact Factor -
Article: An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region.
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ABSTRACT: 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 1926Genetics 10/1999; 153(1):179-219. · 4.01 Impact Factor -
Article: The balance between isoforms of the prickle LIM domain protein is critical for planar polarity in Drosophila imaginal discs.
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ABSTRACT: The tissue polarity mutants in Drosophila include a set of conserved gene products that appear to be involved in the control of cytoskeletal architecture. Here we show that the tissue polarity gene prickle (pk) encodes a protein with a triple LIM domain and a novel domain that is present in human, murine, and Caenorhabditis elegans homologs which we designate PET. Three transcripts have been identified, pk, pkM, and sple, encoding 93-, 100-, and 129-kD conceptual proteins, respectively. The three transcripts span 70 kb and share 6 exons that contain the conserved domains. The pk and sple transcripts are expressed with similar tissue-specific patterns but have qualitatively different activities. The phenotypes of pk mutants, and transgenic flies in which the different isoforms are overexpressed show that the balance between Pk and Sple is critical for the specification of planar polarity. In addition, these phenotypes suggest a tessellation model in which the alignment of wing hairs is dependent on cell shape and need not reflect fine-grained positional information. Lack of both pk and sple transcripts gives a phenotype affecting the whole body surface that is similar to those of dishevelled and frizzled (fz) suggesting a functional relationship between pk and fz signaling.Genes & Development 10/1999; 13(17):2315-27. · 11.66 Impact Factor -
Article: The kakapo mutation affects terminal arborization and central dendritic sprouting of Drosophila motorneurons.
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ABSTRACT: The lethal mutation l(2)CA4 causes specific defects in local growth of neuronal processes. We uncovered four alleles of l(2)CA4 and mapped it to bands 50A-C on the polytene chromosomes and found it to be allelic to kakapo (. Genetics. 146:275- 285). In embryos carrying our kakapo mutant alleles, motorneurons form correct nerve branches, showing that long distance growth of neuronal processes is unaffected. However, neuromuscular junctions (NMJs) fail to form normal local arbors on their target muscles and are significantly reduced in size. In agreement with this finding, antibodies against kakapo (Gregory and Brown. 1998. J. Cell Biol. 143:1271-1282) detect a specific epitope at all or most Drosophila NMJs. Within the central nervous system of kakapo mutant embryos, neuronal dendrites of the RP3 motorneuron form at correct positions, but are significantly reduced in size. At the subcellular level we demonstrate two phenotypes potentially responsible for the defects in neuronal branching: first, transmembrane proteins, which can play important roles in neuronal growth regulation, are incorrectly localized along neuronal processes. Second, microtubules play an important role in neuronal growth, and kakapo appears to be required for their organization in certain ectodermal cells: On the one hand, kakapo mutant embryos exhibit impaired microtubule organization within epidermal cells leading to detachment of muscles from the cuticle. On the other, a specific type of sensory neuron (scolopidial neurons) shows defects in microtubule organization and detaches from its support cells.The Journal of Cell Biology 12/1998; 143(5):1283-94. · 10.26 Impact Factor -
Article: Recovery of a marked translocation strain that will facilitate the isolation of balancer chromosomes in the Mediterranean fruit fly, Ceratitis capitata.
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ABSTRACT: The results of two screens for mutations and chromosomal aberrations in Ceratitis capitata are presented. Three dominant mutations were recovered, including Sb, which is associated with a homozygous lethal translocation between the third and fifth chromosomes, T(3;5)Sb, with the fifth chromosome breakpoint adjacent to y. The T(3;5)Sb chromosome is maintained by selecting for Sb in a T(3;5)Sb, w2 Sb y2 wp/w2 y2 wp stock and can be used to distinguish between other chromosomes carrying differential combinations of the recessive markers w2 y2 wp. The ability to isolate particular marked chromosomes is essential in order to recover an inversion-based balancer chromosome. In addition to the recovery of dominant mutations, gamma-ray induced somatic mosaics of w2 and y2 and zygotic w mosaics were found. The generation of zygotic mosaics following mutagenesis can give mutants with a mosaic germ line that fail to breed true in the first generation. A screen of 22,830 irradiated chromosomes failed to recover variegating alleles of w, although such alleles might be recovered in a larger screen. The high frequency of dominant mutations and the instability at the w locus in our stocks implies a background level of dysgenic activity. These results have implications for the construction and long-term maintenance of genetically modified strains.Genome 05/1998; 41(2):256-65. · 1.65 Impact Factor -
Article: Topological constraints on transvection between white genes within the transposing element TE35B in Drosophila melanogaster.
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ABSTRACT: The transposable element TE35B carries two copies of the white (w) gene at 35B1.2 on the second chromosome. These w genes are suppressed in zeste-1 (z1) mutant background in a synapsis-dependent manner. Single-copy derivatives of the original TE35B stock give red eyes when heterozygous, but zeste eyes when homozygous. TE35B derivatives carrying single, double or triple copies of w were crossed to generate flies carrying from two to five ectopic w genes. Within this range, z1-mediated suppression is insensitive to copynumber and does not distinguish between w genes that are in cis or in trans. Suppression does not require the juxtaposition of even numbers of w genes, but is extremely sensitive to chromosomal topology. When arranged in a tight cluster, in triple-copy TE derivatives, w genes are nonsuppressible. Breakpoints falling within TE35B and separating two functional w genes act as partial suppressors of z1. Similarly, breakpoints immediately proximal or distal to both w genes give partial suppression. This transvection-dependent downregulation of w genes may result from mis-activation of the X-chromosome dosage compensation mechanism.Genetics 08/1997; 146(3):919-37. · 4.01 Impact Factor -
Article: Genetic and phenotypic analysis of the genes of the elbow-no-ocelli region of chromosome 2L of Drosophila melanogaster.
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ABSTRACT: The elbow locus is found to be two genes elA and elB, each of which has a distinct phenotype when mutant. Mutations of the elA gene have a strong phenotype where the wing is markedly disrupted. Mutations of elB are weak, mainly affecting the alula and the wing bristles. The two genes are dominant enhancers of each other. Homozygous deletion of the complete elbow region results in lethality. Situated between the elbow genes is the pupal gene and a locus which when deleted causes a crippled leg phenotype. This locus may be a control region for elbow. Immediately adjacent on the proximal side of elA is the no-ocelli locus. The phenotypes of noc alleles vary from extreme, where the ocelli and associated bristles are absent, to weak where these structures are disrupted. The various noc phenotypes are associated with genetically distinct gene regions, mutations of which act as enhancers of each other. Alleles of el and noc show partial failure of complementation, heterozygotes having weak el or weak noc phenotypes. Alleles of both these genes interact with the antimorphic noc allele Sco.Hereditas 02/1997; 126(1):67-75. · 0.79 Impact Factor -
Article: Rescue of hybrid sterility in crosses between D. melanogaster and D. simulans.
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ABSTRACT: The genetic analysis of reproductive isolation between species of Drosophila has now reached the resolution necessary to start answering one of the fundamental questions of evolution: what is the genetic basis of species differences? A.H. Sturtevant, one of the founders of Drosophila genetics, was fascinated by this question and thought he had found a way to analyse it when he realized that 'Drosophila melanogaster' was actually two species: D. melanogaster and D. simulans. By passing genes between these two species he hoped to investigate their genetic differences directly. No doubt he was disappointed to find that the D. melanogaster/D. simulans hybridization resulted only in unisexual sterile hybrids, a disappointment appreciated all the more by modern evolutionary biologists. Seventy-five years after Sturtevant's description of D. melanogaster/D. simulans hybrid sterility, we have discovered a strain of D. simulans that produces fertile female hybrids in crosses with D. melanogaster. Our discovery promises to bring the enormous resolution of D. melanogaster genetics to the study of reproductive isolation and species differences.Nature 04/1996; 380(6570):157-9. · 36.28 Impact Factor -
Article: Genetic and cytogenetic analysis of the 43A-E region containing the segment polarity gene costa and the cellular polarity genes prickle and spiny-legs in Drosophila melanogaster.
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ABSTRACT: A cytogenetic analysis of the 43A-E region of chromosome 2 in Drosophila melanogaster is presented. Within this interval 27 complementation groups have been identified by extensive F2 screens and ordered by deletion mapping. The region includes the cellular polarity genes prickle and spiny-legs, the segmentation genes costa and torso, the morphogenetic locus sine oculis and is bounded on its distal side by the eye-color gene cinnabar. In addition 19 novel lethal complementation groups and two semi-lethal complementation groups with morphogenetic escaper phenotypes are described.Genetics 10/1993; 135(1):105-15. · 4.01 Impact Factor -
Article: The genetics of a small autosomal region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. VII. Characterization of the region around the snail and cactus loci.
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ABSTRACT: The genetic interval 35C to 36A on chromosome arm 2L of Drosophila melanogaster has been saturated for mutations with visible or lethal phenotypes. 38 loci have been characterized, including several maternal-effect lethals (vasa, Bic-C, chiffon, cactus and cornichon) and several early embryonic lethals, including snail and fizzy. About 130 deletions have been used to order these loci. Complex interactions between mutant alleles have been uncovered in the immediate genetic environs of the snail gene, as has further evidence for an interaction between this region and that including the nearby genes no-ocelli and elbow.Genetics 12/1990; 126(3):679-94. · 4.01 Impact Factor -
Article: A novel transvection phenomenon affecting the white gene of Drosophila melanogaster.
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ABSTRACT: The zeste mutation of Drosophila melanogaster suppresses the expression of white genes in the eye. This suppression is normally dependent on there being two copies of w+ located close to each other in the genome--they may either be in cis (as in a tandem duplication of w+) or in trans, i.e. on homologous chromosomes. Duplicated w+ genes carried by a giant transposing element, TE146(Z), are suppressed by z whether they are in direct (tandem) or inverted order. The tandem form of the TE is very sensitive to a rearrangement on the homologous chromosome--many rearrangements with breakpoints "opposite" the TE's insertion site prevent the interaction between the white genes on a z background. These aberrations act as dominant suppressors of zeste that are specific to the tandemly duplicated form of TE146(Z). The inverted form of the TE146(Z) presumably pairs as a hairpin loop; this is more stable than the tandem form by the criterion that its zeste phenotype is unaffected by any of the aberrations. This effect of rearrangements has been used as the basis for a screen, gamma-ray induced aberrations with at least one breakpoint opposite the TE site were recovered by their suppression of the zeste phenotype.Genetics 10/1990; 126(1):167-76. · 4.01 Impact Factor -
Article: A genetic basis for the inviability of hybrids between sibling species of Drosophila.
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ABSTRACT: A mutation of Drosophila melanogaster whose only known effect is the rescue of otherwise lethal interspecific hybrids has been characterized. This mutation, Hmr, maps to 1-31.84 (9D1-9E4). Hmr may be the consequence of a P element insertion. It rescues hybrid males from the cross of D. melanogaster females to males of its three sibling species, D. simulans, D. mauritiana and D. sechellia. This rescue is recessive, since hybrid males that carry both Hmr and a duplication expected to be Hmr+ are not rescued. Hmr also rescues the otherwise inviable female hybrids from the cross of compound-X D. melanogaster females to males of its sibling species. This rescue is also recessive, since a compound-X heterozygous for Hmr does not rescue. Another mutation, discovered on the In(1)AB chromosome of D. melanogaster, is also found to rescue normally inviable species hybrids: unlike Hmr, however, In(1)AB rescues hybrid females from the cross of In(1)AB/Y males to sibling females, as well as hybrid males from the cross of In(1)AB females to sibling males. These data are interpreted on the basis of a model for the genetic basis of hybrid inviability of complementary genes.Genetics 05/1990; 124(4):909-20. · 4.01 Impact Factor -
Article: Interactions between WHITE Genes Carried by a Large Transposing Element and the ZESTE Allele in DROSOPHILA MELANOGASTER.
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ABSTRACT: TE146, a large transposing element of Drosophila melanogaster, carries two copies of the white and roughest genes in tandem. In consequence, z(1)w( 11E4); TE146(Z)/+ flies have a zeste (lemon-yellow) eye color. However, one in 10(3)TE146 chromosomes mutates to a red-eyed form. The majority of these "spontaneous red" (SR) derivatives of TE146 have only one copy of the white gene and are, cytologically, two- to three-banded elements, rather than six-banded as their progenitor. The SR forms of TE146 are also unstable and give zeste-colored forms with a frequency of about one in 10(4). One such "spontaneous zeste" (SZ) derivative carries duplicated white genes as an inverted, rather than a tandem, repeat. The genetic instability of this inverted repeat form of TE146 is different from that of the original tandem repeat form. In particular, the inverted repeat form frequently produces derivatives with internal rearrangements of the TE and gives a much lower frequency of SR forms. In addition, two novel features of the interaction between w(+) alleles in a zeste background have been found. First, copies of w( +) can become insensitive to suppression by zeste even when paired. Second, an inversion breakpoint may disrupt the pairing between two adjacent w(+) alleles, necessary for their suppression by zeste, without physically separating them.Genetics 04/1986; 112(3):551-75. · 4.01 Impact Factor -
Article: A preliminary genetic analysis of TE146, a very large transposing element of Drosophila melanogaster
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ABSTRACT: TE146 is a transposing element (TE) consisting of six polytene chromosome bands that has inserted into the no-ocelli (noc 250) locus. This member of Ising's TE family carries two copies of the white and roughest loci. TE146 is lost from noc with a spontaneous frequency of approximately 1 in 22000 chromosomes. All spontaneous losses are accompanied by the reversion of the noc mutation associated with the TE. The TE is associated with fold-back (FB) sequences. The losses of TE146 retain fold-back homology at noc. Of 26 -ray-induced losses of TE146, 16 are gross deletions, removing loci neighboring noc and ten are not. The non-deleted -ray-induced losses are either noc – and rst + or noc + and rst –. The white+ genes of TE146 are dosage compensated since w/Y; TE146/+ and w/w; TE146/+ flies are sexually dimorphic for eye color. These w + genes are also suppressed by zeste since z w; TE146/+ flies have zeste-colored eyes.Chromosoma 05/1985; 92(2):116-123. · 3.85 Impact Factor -
Article: The genetic analysis of a large transposing element of Drosophila melanogaster
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ABSTRACT: A member of Ising's family of large transposing elements (TEs) has inserted into, or very near, the crinkled (ck, 2–50) locus. This TE (TE36) carries functional alleles of both the white and roughest loci, and causes a hypomorphic mutation of ck. The TE is visible in polytene chromosomes as a two-banded insertion between 35B9 and 35C1. These bands show homology to foldback (FB) elements by in situ hybridization. All spontaneous losses of TE36 remain mutant for ck and retain sequences homologous to FB at the site of TE's insertion. TE36 carries only one functional copy of w +, by the criterion that z w, TE36/ + flies are wild-type for eye color but z w; TE36/TE36 flies are zeste. This white+ gene is dosage compensated since w/Y; TE36/+ males have twice as much eye pigment as w/w; TE36/ + females. A form of the TE that has four polytene chromosome bands and expresses twice as much pigment as TE36 has been recovered. However, its white genes are not suppressed by zeste.Chromosoma 11/1984; 91(1):54-64. · 3.85 Impact Factor
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- Genetics (10)
- Chromosoma (2)
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Institutions
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1984–2000
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University of Cambridge
- Department of Genetics
Cambridge, ENG, United Kingdom
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1990
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University of Geneva
Carouge, GE, Switzerland
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