Articles de revues : « Drosophila Molecular genetics »

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Yedvobnick, B., M. A. T. Muskavitch, K. A. Wharton, M. E. Halpern, E. Paul, B. G. Grimwade, and S. Artavanis-Tsakonas. "Molecular Genetics of Drosophila Neurogenesis." Cold Spring Harbor Symposia on Quantitative Biology 50 (January 1, 1985): 841–54. http://dx.doi.org/10.1101/sqb.1985.050.01.102.

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Ip, Y. Tony, and Michael Levine. "Molecular genetics of Drosophila immunity." Current Opinion in Genetics & Development 4, no. 5 (October 1994): 672–77. http://dx.doi.org/10.1016/0959-437x(94)90133-n.

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Montell, Craig. "Molecular genetics of drosophila vision." BioEssays 11, no. 2-3 (August 1989): 43–48. http://dx.doi.org/10.1002/bies.950110202.

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Morton, R. A. "Evolution of Drosophila insecticide resistance." Genome 36, no. 1 (February 1, 1993): 1–7. http://dx.doi.org/10.1139/g93-001.

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The impact of insecticide resistance is well documented. It includes the toxic effects of pesticides on the environment and the cost of the increased amounts of insecticides required to effectively control resistant insects. Resistance evolves by the selection of genes that confer tolerance to insecticides. Several resistance genes have been identified and cloned in Drosophila, including genes for mutant target molecules and genes that increase insecticide degradation. Drosophila is a useful system to understand the evolution of quantitative traits in general as well as the population genetics of insecticide resistance. Through it, we may hope to understand the relationship between discrete genetic change and continuously varying characters. In addition, molecular genetic techniques developed using Drosophila can eventually be transferred to other insects in order to help control pest populations.Key words: insecticide resistance, evolution of tolerance, selection of resistant genes, molecular genetics, Drosophila.

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Lange, B. W., C. H. Langley, and W. Stephan. "Molecular evolution of Drosophila metallothionein genes." Genetics 126, no. 4 (December 1, 1990): 921–32. http://dx.doi.org/10.1093/genetics/126.4.921.

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Abstract The metallothionein genes of Drosophila melanogaster, Mtn and Mto, may play an important role in heavy metal detoxification. Several different tandem duplications of Mtn have been shown to increase cadmium and copper tolerance, as well as Mtn expression. In order to investigate the possibility of increased selection for duplications of these genes in natural populations exposed to high levels of heavy metals, we compared the frequencies of such duplications among flies collected from metal-contaminated and non-contaminated orchards in Pennsylvania, Tennessee and Georgia. Restriction enzyme analysis was used to screen 1666 wild third chromosomes for Mtn duplications and a subset (327) of these lines for Mto duplications. The frequency of pooled Mtn duplications found ranged from 0% to 20%, and was not significantly higher at the contaminated sites. No Mto duplications were identified. Estimates of sequence diversity at the Mtn locus among a subsample (92) of the duplication survey were obtained using four-cutter analysis. This analysis revealed a low level of polymorphism, consistent with both selection at the Mtn locus, and a fairly recent origin for the duplications. To further examine this hypothesis, we sequenced an Mtn allele of Drosophila simulans and measured the amount of nucleotide sequence divergence between D. simulans and its sibling species D. melanogaster. The levels of silent nucleotide polymorphism and divergence in the Mtn region were compared with those in the Adh region, using the neutrality test of R.R. Hudson, M. Kreitman and M. Aguadé.

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VAN DER LINDE, KIM, DAVID HOULE, GREG S. SPICER, and SCOTT J. STEPPAN. "A supermatrix-based molecular phylogeny of the family Drosophilidae." Genetics Research 92, no. 1 (February 2010): 25–38. http://dx.doi.org/10.1017/s001667231000008x.

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SummaryThe genus Drosophila is diverse and heterogeneous and contains a large number of easy-to-rear species, so it is an attractive subject for comparative studies. The ability to perform such studies is currently compromised by the lack of a comprehensive phylogeny for Drosophila and related genera. The genus Drosophila as currently defined is known to be paraphyletic with respect to several other genera, but considerable uncertainty remains about other aspects of the phylogeny. Here, we estimate a phylogeny for 176 drosophilid (12 genera) and four non-drosophilid species, using gene sequences for up to 13 different genes per species (average: 4333 bp, five genes per species). This is the most extensive set of molecular data on drosophilids yet analysed. Phylogenetic analyses were conducted with maximum-likelihood (ML) and Bayesian approaches. Our analysis confirms that the genus Drosophila is paraphyletic with 100% support in the Bayesian analysis and 90% bootstrap support in the ML analysis. The subgenus Sophophora, which includes Drosophila melanogaster, is the sister clade of all the other subgenera as well as of most species of six other genera. This sister clade contains two large, well-supported subclades. The first subclade contains the Hawaiian Drosophila, the genus Scaptomyza, and the virilis-repleta radiation. The second contains the immigrans-tripunctata radiation as well as the genera Hirtodrosophila (except Hirtodrosophila duncani), Mycodrosophila, Zaprionus and Liodrosophila. We argue that these results support a taxonomic revision of the genus Drosophila.

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Anderson, Jennifer A., Yun S. Song, and Charles H. Langley. "Molecular Population Genetics of Drosophila Subtelomeric DNA." Genetics 178, no. 1 (January 2008): 477–87. http://dx.doi.org/10.1534/genetics.107.083196.

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Bender, Welcome W. "Molecular Lessons from the Drosophila Bithorax Complex." Genetics 216, no. 3 (November 2020): 613–17. http://dx.doi.org/10.1534/genetics.120.303708.

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The Genetics Society of America’s (GSA’s) Edward Novitski Prize recognizes a single experimental accomplishment or a body of work in which an exceptional level of creativity, and intellectual ingenuity, has been used to design and execute scientific experiments to solve a difficult problem in genetics. The 2020 recipient is Welcome W. Bender of Harvard Medical School, recognizing his creativity and ingenuity in revealing the molecular nature and regulation of the bithorax gene complex.

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Curtis, D., S. H. Clark, A. Chovnick, and W. Bender. "Molecular analysis of recombination events in Drosophila." Genetics 122, no. 3 (July 1, 1989): 653–61. http://dx.doi.org/10.1093/genetics/122.3.653.

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Abstract The locations of crossover junctions and gene conversion tracts, isolated in the rosy gene of Drosophila melanogaster, were determined using DNA sequencing and denaturing gradient gel electrophoresis. Frequent DNA sequence polymorphisms between the parental genes served as unselected genetic markers. All conversion tracts were continuous, and half of the reciprocal crossover events had conversion tracts at the crossover junction. These experiments have also identified the sequence polymorphisms responsible for altered gene expression in two naturally occurring rosy variants.

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Clark, Andrew G., and Lei Wang. "Molecular Population Genetics of Drosophila Immune System Genes." Genetics 147, no. 2 (October 1, 1997): 713–24. http://dx.doi.org/10.1093/genetics/147.2.713.

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A striking aspect of many vertebrate immune system genes is the exceptionally high level of polymorphism they harbor. A convincing case can be made that this polymorphism is driven by the diversity of pathogens that face selective pressures to evade attack by the host immune system. Different organisms accomplish a defense against diverse pathogens through mechanisms that differ widely in their requirements for specific recognition. It has recently been shown that innate defense mechanisms, which use proteins with broad-spectrum bactericidal properties, are common to both primitive and advanced organisms. In this study we characterize DNA sequence variation in six pathogen defense genes of Drosophila melanogaster and D. mauritiana, including Andropin; cecropin genes CecA1, CecA2, CecB, and CecC; and Diptericin. The necessity for protection against diverse pathogens, which themselves may evolve resistance to insect defenses, motivates a population-level analysis. Estimates of variation levels show that the genes are not exceptionally polymorphic, but Andropin and Diptericin have patterns of variation that differ significantly from neutrality. Patterns of interpopulation and interspecific differentiation also reveal differences among the genes in evolutionary forces.

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Newfeld, Stuart J., Richard W. Padgett, Seth D. Findley, Brent G. Richter, Michele Sanicola, Margaret de Cuevas, and William M. Gelbart. "Molecular Evolution at the decapentaplegic Locus in Drosophila." Genetics 145, no. 2 (February 1, 1997): 297–309. http://dx.doi.org/10.1093/genetics/145.2.297.

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Using an elaborate set of cis-regulatory sequences, the decapentaplegic (dpp) gene displays a dynamic pattern of gene expression during development. The C-terminal portion of the DPP protein is processed to generate a secreted signaling molecule belonging to the transforming growth factor-β (TGF-β) family. This signal, the DPP ligand, is able to influence the developmental fates of responsive cells in a concentration-dependent fashion. Here we examine the sequence level organization of a significant portion of the dpp locus in Drosophila melanogaster and use interspecific comparisons with D. simulans, D. pseudoobscura and D.virilis to explore the molecular evolution of the gene. Our interspecific analysis identified significant selective constraint on both the nucleotide and amino acid sequences. As expected, interspecific comparison of protein coding sequences shows that the C-terminal ligand region is highly conserved. However, the central portion of the protein is also conserved, while the N-terminal third is quite variable. Comparison of noncoding regions reveals significant stretches of nucleotide identity in the 3′ untranslated portion of exon 3 and in the intron between exons 2 and 3. An examination of cDNA sequences representing five classes of dpp transcripts indicates that these transcripts encode the same polypeptide.

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Perrin, L., and J. M. Dura. "Molecular genetics of the Alhambra ( Drosophila AF10) complex locus of Drosophila." Molecular Genetics and Genomics 272, no. 2 (July 16, 2004): 156–61. http://dx.doi.org/10.1007/s00438-004-1042-4.

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Zouros, E. "Advances in the genetics of reproductive isolation in Drosophila." Genome 31, no. 1 (January 1, 1989): 211–20. http://dx.doi.org/10.1139/g89-036.

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Speciation genetics is defined as the study of genetic events and processes that differentiate the probabilities that genetic material from individual members of a population will co-occur in individuals of some future generation. It follows that phenotypic attributes that contribute to this differentiation of probabilities (e.g., mating preferences, sterility, or infertility of individuals from certain types of matings) constitute the phenotype of speciation, and genetic loci that may affect these phenotypic attributes can be considered as speciation genes. The literature on genetic differences between hybridizable species of Drosophila that are responsible for morphological differences, mating preferences, hybrid inviability, and hybrid sterility are reviewed with special reference to the species pair D. mojavensis – D. arizonensis. The case for the involvement of karyotypic changes in speciation in rodents is briefly discussed. It is concluded that no major advance has been made in the speciation genetics of Drosophila since Dobzhansky initiated the field 40 years ago. Yet, the identification of several gene loci that cause hybrid inviability or sterility may open the way to the understanding of reproductive isolation at the molecular level. It is not clear whether this approach will lead to general molecular mechanisms underlying the speciation process.Key words: speciation genetics, hybrid sterility, reproductive isolation, Drosophila.

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Matzkin, Luciano M. "The Molecular Basis of Host Adaptation in Cactophilic Drosophila: Molecular Evolution of a Glutathione S-Transferase Gene (GstD1) in Drosophila mojavensis." Genetics 178, no. 2 (February 2008): 1073–83. http://dx.doi.org/10.1534/genetics.107.083287.

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Griswold, C. M., A. L. Matthews, K. E. Bewley, and J. W. Mahaffey. "Molecular characterization and rescue of acatalasemic mutants of Drosophila melanogaster." Genetics 134, no. 3 (July 1, 1993): 781–88. http://dx.doi.org/10.1093/genetics/134.3.781.

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Abstract The enzyme catalase protects aerobic organisms from oxygen-free radical damage by converting hydrogen peroxide to molecular oxygen and water before it can decompose to form the highly reactive hydroxyl radical. Hydroxyl radicals are the most deleterious of the activated oxygen intermediates found in aerobic organisms. If formed, they can react with biological molecules in their proximity; the ensuing damage has been implicated in the increasing risk of disease and death associated with aging. To study further the regulation and role of catalase we have undertaken a molecular characterization of the Drosophila catalase gene and two potentially acatalasemic alleles. We have demonstrated that a previously existing allele, Catn4, likely contains a null mutation, a mutation which blocks normal translation of the encoded mRNA. The Catn1 mutation appears to cause a significant change in the protein sequence; however, it is unclear why this change leads to a nonfunctioning protein. Viability of these acatalasemic flies can be restored by transformation with the wild-type catalase gene; hence, we conclude that the lethality of these genotypes is due solely to the lack of catalase. The availability of flies with transformed catalase genes has allowed us to address the effect of catalase levels on aging in Drosophila. Though lack of catalase activity caused decreased viability and life span, increasing catalase activity above wild-type levels had no effect on normal life span.

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Takano-Shimizu, Toshiyuki. "Local Recombination and Mutation Effects on Molecular Evolution in Drosophila." Genetics 153, no. 3 (November 1, 1999): 1285–96. http://dx.doi.org/10.1093/genetics/153.3.1285.

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Abstract I studied the cause of the significant difference in the synonymous-substitution pattern found in the achaete-scute complex genes in two Drosophila lineages, higher codon bias in Drosophila yakuba, and lower bias in D. melanogaster. Besides these genes, the functionally unrelated yellow gene showed the same substitution pattern, suggesting a region-dependent phenomenon in the X-chromosome telomere. Because the numbers of A/T → G/C substitutions were not significantly different from those of G/C → A/T in the yellow noncoding regions of these species, a AT/GC mutational bias could not completely account for the synonymous-substitution biases. In contrast, we did find an ~14-fold difference in recombination rates in the X-chromosome telomere regions between the two species, suggesting that the reduction of recombination rates in this region resulted in the reduction of the efficacy of selection in D. melanogaster. In addition, the D. orena yellow showed a 5% increase in the G + C content at silent sites in the coding and noncoding regions since the divergence from D. erecta. This pattern was significantly different from those at the orena Adh and Amy loci. These results suggest that local changes in recombination rates and mutational pressures are contributing to the irregular synonymous-substitution patterns in Drosophila.

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Anderson, Jennifer A., William D. Gilliland, and Charles H. Langley. "Molecular Population Genetics and Evolution of Drosophila Meiosis Genes." Genetics 181, no. 1 (November 3, 2008): 177–85. http://dx.doi.org/10.1534/genetics.108.093807.

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Wu, C. H. "Molecular characterization of Drosophila NELF." Nucleic Acids Research 33, no. 4 (February 23, 2005): 1269–79. http://dx.doi.org/10.1093/nar/gki274.

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Carulli, J. P., D. E. Krane, D. L. Hartl, and H. Ochman. "Compositional heterogeneity and patterns of molecular evolution in the Drosophila genome." Genetics 134, no. 3 (July 1, 1993): 837–45. http://dx.doi.org/10.1093/genetics/134.3.837.

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Abstract The rates and patterns of molecular evolution in many eukaryotic organisms have been shown to be influenced by the compartmentalization of their genomes into fractions of distinct base composition and mutational properties. We have examined the Drosophila genome to explore relationships between the nucleotide content of large chromosomal segments and the base composition and rate of evolution of genes within those segments. Direct determination of the G + C contents of yeast artificial chromosome clones containing inserts of Drosophila melanogaster DNA ranging from 140-340 kb revealed significant heterogeneity in base composition. The G + C content of the large segments studied ranged from 36.9% G + C for a clone containing the hunchback locus in polytene region 85, to 50.9% G + C for a clone that includes the rosy region in polytene region 87. Unlike other organisms, however, there was no significant correlation between the base composition of large chromosomal regions and the base composition at fourfold degenerate nucleotide sites of genes encompassed within those regions. Despite the situation seen in mammals, there was also no significant association between base composition and rate of nucleotide substitution. These results suggest that nucleotide sequence evolution in Drosophila differs from that of many vertebrates and does not reflect distinct mutational biases, as a function of base composition, in different genomic regions. Significant negative correlations between codon-usage bias and rates of synonymous site divergence, however, provide strong support for an argument that selection among alternative codons may be a major contributor to variability in evolutionary rates within Drosophila genomes.

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Low, Wai Yee, Hooi Ling Ng, Craig J. Morton, Michael W. Parker, Philip Batterham, and Charles Robin. "Molecular Evolution of GlutathioneS-Transferases in the Genus Drosophila." Genetics 177, no. 3 (November 2007): 1363–75. http://dx.doi.org/10.1534/genetics.107.075838.

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Coté, Babette, Welcome Bender, Daniel Curtis, and Arthur Chovnick. "MOLECULAR MAPPING OF THE ROSY LOCUS IN DROSOPHILA MELANOGASTER." Genetics 112, no. 4 (April 1, 1986): 769–83. http://dx.doi.org/10.1093/genetics/112.4.769.

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ABSTRACT The DNA from the chromosomal region of the Drosophila rosy locus has been examined in 83 rosy mutant strains. Several spontaneous and radiation-induced alleles were associated with insertions and deletions, respectively. The lesions are clustered in a 4-kb region. Some of the alleles identified on the DNA map have been located on the genetic map by fine-structure recombination experiments. The genetic and molecular maps are collinear, and the alignment identifies the DNA location of the rosy control region. A rosy RNA of 4.5 kb has been identified; its 5' end lies in or near the control region.

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Rosato, E., A. A. Peixoto, G. Barbujani, R. Costa, and C. P. Kyriacou. "Molecular polymorphism in the period gene of Drosophila simulans." Genetics 138, no. 3 (November 1, 1994): 693–707. http://dx.doi.org/10.1093/genetics/138.3.693.

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Abstract The threonine-glycine (Thr-Gly) repeat region of the period (per) gene of eight natural populations of Drosophila simulans from Europe and North Africa was analyzed by polymerase chain reaction, DNA sequencing and heteroduplex formation. Five different length alleles encoding 21, 23, 25 and two different kinds of 24 Thr-Gly pairs in the uninterrupted repeat were found. In the 3' region flanking the repeat 6 nucleotide substitutions (3 synonymous, 3 replacement) were observed in three different combinations that we called haplotypes I, II and III. The complete linkage disequilibrium observed between the haplotypes and these length variants allowed us to infer from the repeat length, the DNA sequence at the 3' polymorphic sites. The haplotypes were homogeneously distributed across Europe and North Africa. The data show statistically significant departures from neutral expectations according to the Tajima test. The results suggest that balancing selection might have played a role in determining the observed levels and patterns of genetic diversity at the per gene in D. simulans.

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Eggleston, William B., Nac R. Rim, and Johng K. Lim. "Molecular Characterization of hobo-Mediated Inversions in Drosophila melanogaster." Genetics 144, no. 2 (October 1, 1996): 647–56. http://dx.doi.org/10.1093/genetics/144.2.647.

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Abstract The structure of chromosomal inversions mediated by hobo transposable elements in the Uc-1 X chromosome was investigated using cytogenetic and molecular methods. Uc-1 contains a phenotypically silent hobo element inserted in an intron of the Notch locus. Cytological screening identified six independent Notch mutations resulting from chromosomal inversions with one breakpoint at cytological position 3C7, the location of Notch. In situ hybridization to salivary gland polytene chromosomes determined that both ends of each inversion contained hobo and Notch sequences. Southern blot analyses showed that both breakpoints in each inversion had hobo-Notch junction fragments indistinguishable in structure from those present in the Uc-1 X chromosome prior to the rearrangements. Polymerase chain reaction amplification of the 12 hobo-Notch junction fragments in the six inversions, followed by DNA sequence analysis, determined that each was identical to one of the two hobo-Notch junctions present in Uc-1. These results are consistent with a model in which hobo-mediated inversions result from homologous pairing and recombination between a pair of hobo elements in reverse orientation.

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Adler, P. N., C. Vinson, W. J. Park, S. Conover, and L. Klein. "Molecular structure of frizzled, a Drosophila tissue polarity gene." Genetics 126, no. 2 (October 1, 1990): 401–16. http://dx.doi.org/10.1093/genetics/126.2.401.

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Abstract The function of the frizzled (fz) locus is required to coordinate the cytoskeletons of pupal epidermal cells so that a parallel array of cuticular hairs and bristles is produced. We report here the molecular cloning and characterization of the fz locus. The locus is very large. Mutations that inactivate the gene are spread over 100 kb of genomic DNA. The major mRNA product of the gene is a 4-kb RNA that is encoded by 5 exons spread over more than 90 kb of genomic DNA. Conceptual translation of this mRNA indicates that it encodes an integral membrane protein that is likely to contain both extracellular and cytoplasmic domains.

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Maroni, Gustavo, Edward Otto, and Donna Lastowski-Perry. "MOLECULAR AND CYTOGENETIC CHARACTERIZATION OF A METALLOTHIONEIN GENE OF DROSOPHILA." Genetics 112, no. 3 (March 1, 1986): 493–504. http://dx.doi.org/10.1093/genetics/112.3.493.

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ABSTRACT A chromosomal DNA segment containing the metallothionein gene was isolated from a genomic library of Drosophila melanogaster using a previously characterized cDNA of this species as a probe. A segment of 1543 base pair (bp) was sequenced and found to include the cDNA sequence interrupted by one small intron. Several lines of evidence indicate that there is a single copy of the metallothionein gene (Mtn) in Drosophila; any other related genes, if they occur, must be sufficiently different that they are not detectable by our probe, even under hybridization conditions of reduced stringency. According to in situ hybridization and deletion mapping, Mtn is located in the right arm of the third chromosome in region 85E10-15. Within 300 bases upstream of the apparent site of transcription initiation, there are several short intervals very similar to the 12-bp segments considered to be responsible for metal regulation in mammalian systems.

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Sokolowski, Marla B. "Drosophila: Genetics meets behaviour." Nature Reviews Genetics 2, no. 11 (November 2001): 879–90. http://dx.doi.org/10.1038/35098592.

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Begun, David J., Penn Whitley, Bridget L. Todd, Heidi M. Waldrip-Dail, and Andrew G. Clark. "Molecular Population Genetics of Male Accessory Gland Proteins in Drosophila." Genetics 156, no. 4 (December 1, 2000): 1879–88. http://dx.doi.org/10.1093/genetics/156.4.1879.

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Abstract Drosophila seminal proteins have an unusually high rate of molecular sequence evolution, suggesting either a high rate of neutral substitution or rapid adaptive evolution. To further quantify patterns of polymorphism and divergence in genes encoding seminal proteins, also called accessory gland proteins (Acp’s), we conducted a sequencing survey of 10 Acp genes in samples of Drosophila melanogaster and D. simulans (Acp29AB, Acp32CD, Acp33A, Acp36DE, Acp53Ea, Acp62F, Acp63F, Acp76A, Acp95EF, and Acp98AB). Mean heterozygosity at replacement sites in D. simulans was 0.0074 for Acp genes and 0.0013 for a set of 19 non-Acp genes, and mean melanogaster-simulans divergence at replacement sites was 0.0497 for Acp genes and 0.0107 at non-Acp genes. The elevated divergence of Acp genes is thus accompanied by elevated within-species polymorphism. In addition to the already-reported departures of Acp26A, Acp29AB, and Acp70A from neutrality, our data reject neutrality at Acp29AB and Acp36DE in the direction of excess replacements in interspecific comparisons.

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Lovering, R., N. Harden, and M. Ashburner. "The molecular structure of TE146 and its derivatives in Drosophila melanogaster." Genetics 128, no. 2 (June 1, 1991): 357–72. http://dx.doi.org/10.1093/genetics/128.2.357.

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Abstract TE146 is a giant transposon of Drosophila melanogaster. It carries two copies of the white and roughest genes, normally found on the X chromosome. The structure of this transposon has been studied at the molecular level. TE146 may transpose to new chromosome positions, excise and be lost from the genome or undergo internal rearrangements. The termini of TE146 are foldback DNA elements (FB); the transposon also carries two internal FB elements. Loss or internal rearrangement of TE146 involves recombination between different FB elements. These events have been mapped molecularly, by taking advantage of the fact that the FB sequences are composed largely of a regular 155-bp repeat sequence that is cut by the restriction enzyme TaqI, and are shown to be nonrandom. We suggest that these FB-FB exchange events occur by mitotic sister-chromatid exchange in the premeiotic germ line.

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Wilkins, Adam S. "Developmental genetics of drosophila." BioEssays 21, no. 8 (July 29, 1999): 710–11. http://dx.doi.org/10.1002/(sici)1521-1878(199908)21:8<710::aid-bies11>3.0.co;2-d.

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Shieh, Bih-Hwa. "Molecular genetics of retinal degeneration: A Drosophila perspective." Fly 5, no. 4 (October 1, 2011): 356–68. http://dx.doi.org/10.4161/fly.5.4.17809.

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Deng, Wu-Min. "Molecular genetics of cancer and tumorigenesis: Drosophila models." Journal of Genetics and Genomics 38, no. 10 (October 2011): 429–30. http://dx.doi.org/10.1016/j.jgg.2011.09.010.

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Williams, Scott M., and Leonard G. Robbins. "Molecular genetic analysis of Drosophila rDNA arrays." Trends in Genetics 8, no. 10 (October 1992): 335–40. http://dx.doi.org/10.1016/0168-9525(92)90277-b.

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Small, Stephen, and David N. Arnosti. "Transcriptional Enhancers in Drosophila." Genetics 216, no. 1 (September 2020): 1–26. http://dx.doi.org/10.1534/genetics.120.301370.

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Key discoveries in Drosophila have shaped our understanding of cellular “enhancers.” With a special focus on the fly, this chapter surveys properties of these adaptable cis-regulatory elements, whose actions are critical for the complex spatial/temporal transcriptional regulation of gene expression in metazoa. The powerful combination of genetics, molecular biology, and genomics available in Drosophila has provided an arena in which the developmental role of enhancers can be explored. Enhancers are characterized by diverse low- or high-throughput assays, which are challenging to interpret, as not all of these methods of identifying enhancers produce concordant results. As a model metazoan, the fly offers important advantages to comprehensive analysis of the central functions that enhancers play in gene expression, and their critical role in mediating the production of phenotypes from genotype and environmental inputs. A major challenge moving forward will be obtaining a quantitative understanding of how these cis-regulatory elements operate in development and disease.

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Wharton, Kristi, Robert P. Ray, Seth D. Findley, Holly E. Duncan та William M. Gelbart. "Molecular Lesions Associated With Alleles of decapentuplegic Identify Residues Necessary for TGF-β/BMP Cell Signaling in Drosophila melanogaster". Genetics 142, № 2 (1 лютого 1996): 493–505. http://dx.doi.org/10.1093/genetics/142.2.493.

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Abstract We have identified the molecular lesions associated with six point mutations in the Drosophila TGF-β homologue decapentaplegic (dpp). The sites of these mutations define residues within both the pro and ligand regions that are essential for dpp function in vivo. While all of these mutations affect residues that are highly conserved among TGF-β superfamily members, the phenotypic consequences of the different alleles are quite distinct. Through an analysis of these mutant phenotypes, both in cuticle preparations and with molecular probes, we have assessed the functional significance of specific residues that are conserved among the different members of the superfamily. In addition, we have tested for conditional genetic interactions between the different alleles. We show that two of the alleles are temperature sensitive for the embyronic functions of dpp, such that these alleles are not only embryonic viable as homozygotes but also partially complement other dpp hypomorphs at low temperatures. Our results are discussed with regard to in vitro mutagenesis data on other TGF-β-like molecules, as well as with regard to the regulation of dpp cell signaling in Drosophila.

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Hudson, Richard R., Martin Kreitman, and Montserrat Aguadé. "A Test of Neutral Molecular Evolution Based on Nucleotide Data." Genetics 116, no. 1 (May 1, 1987): 153–59. http://dx.doi.org/10.1093/genetics/116.1.153.

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ABSTRACT The neutral theory of molecular evolution predicts that regions of the genome that evolve at high rates, as revealed by interspecific DNA sequence comparisons, will also exhibit high levels of polymorphism within species. We present here a conservative statistical test of this prediction based on a constant-rate neutral model. The test requires data from an interspecific comparison of at least two regions of the genome and data on levels of intraspecific polymorphism in the same regions from at least one species. The model is rejected for data from the region encompassing the Adh locus and the 5′ flanking sequence of Drosophila melanogaster and Drosophila sechellia. The data depart from the model in a direction that is consistent with the presence of balanced polymorphism in the coding region.

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Ballard, J. W., and M. Kreitman. "Unraveling selection in the mitochondrial genome of Drosophila." Genetics 138, no. 3 (November 1, 1994): 757–72. http://dx.doi.org/10.1093/genetics/138.3.757.

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Abstract We examine mitochondrial DNA variation at the cytochrome b locus within and between three species of Drosophila to determine whether patterns of variation conform to the predictions of neutral molecular evolution. The entire 1137-bp cytochrome b locus was sequenced in 16 lines of Drosophila melanogaster, 18 lines of Drosophila simulans and 13 lines of Drosophila yakuba. Patterns of variation depart from neutrality by several test criteria. Analysis of the evolutionary clock hypothesis shows unequal rates of change along D. simulans lineages. A comparison within and between species of the ratio of amino acid replacement change to synonymous change reveals a relative excess of amino acid replacement polymorphism compared to the neutral prediction, suggestive of slightly deleterious or diversifying selection. There is evidence for excess homozygosity in our world wide sample of D. melanogaster and D. simulans alleles, as well as a reduction in the number of segregating sites in D. simulans, indicative of selective sweeps. Furthermore, a test of neutrality for codon usage shows the direction of mutations at third positions differs among different topological regions of the gene tree. The analyses indicate that molecular variation and evolution of mtDNA are governed by many of the same selective forces that have been shown to govern nuclear genome evolution and suggest caution be taken in the use of mtDNA as a "neutral" molecular marker.

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Gausz, Janos, Lucinda M. C. Hall, Anne Spierer, and Pierre Spierer. "MOLECULAR GENETICS OF THE ROSY-ACE REGION OF DROSOPHILA MELANOGASTER." Genetics 112, no. 1 (January 1, 1986): 65–78. http://dx.doi.org/10.1093/genetics/112.1.65.

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ABSTRACT Three hundred and fifteen kilobases of DNA from the rosy-Ace region on chromosome 3R of D. melanogaster have previously been cloned and extensively characterized. We describe the isolation of nine new deficiency mutants that break within the 315-kb interval. The position of these breakpoints on the DNA map was determined by in situ and Southern hybridization. Further, we more precisely mapped the breakpoints of several deletions previously analyzed. The results permit us to delimit sequences essential to the known complementation groups in the region within approximately 20 kb in most cases. However, one gene, B16-1, is shown to contain essential sequences that span about 50 kb. Also, we demonstrate by overlapping deficiencies that a 45-kb DNA segment from the region, which includes one known complementation group, allows limited survival when deleted.

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Kovacevic, Miro, and Stephen W. Schaeffer. "Molecular Population Genetics of X-Linked Genes in Drosophila pseudoobscura." Genetics 156, no. 1 (September 1, 2000): 155–72. http://dx.doi.org/10.1093/genetics/156.1.155.

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Abstract This article presents a nucleotide sequence analysis of 500 bp determined in each of five X-linked genes, runt, sisterlessA, period, esterase 5, and Heat-shock protein 83, in 40 Drosophila pseudoobscura strains collected from two populations. Estimates of the neutral migration parameter for the five loci show that gene flow among D. pseudoobscura populations is sufficient to homogenize inversion frequencies across the range of the species. Nucleotide diversity at each locus fails to reject a neutral model of molecular evolution. The sample of 40 chromosomes included six Sex-ratio inversions, a series of three nonoverlapping inversions that are associated with a strong meiotic drive phenotype. The selection driven by the Sex-ratio meiotic drive element has not fixed variation across the X chromosome of D. pseudoobscura because, while significant linkage disequilibrium was observed within the sisterlessA, period, and esterase 5 genes, we did not find evidence for nonrandom association among loci. The Sex-ratio chromosome was estimated to be 25,000 years old based on the decomposition of linkage disequilibrium between esterase 5 and Heat-shock protein 83 or 1 million years old based on the net divergence of esterase 5 between Standard and Sex-ratio chromosomes. Genetic diversity was depressed within esterase 5 within Sex-ratio chromosomes, while the four other genes failed to show a reduction in heterozygosity in the Sex-ratio background. The reduced heterogeneity in esterase 5 is due either to its location near one of the Sex-ratio inversion breakpoints or that it is closely linked to a gene or genes responsible for the Sex-ratio meiotic drive system.

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Yedvobnick, B., D. Smoller, P. Young, and D. Mills. "Molecular analysis of the neurogenic locus mastermind of Drosophila melanogaster." Genetics 118, no. 3 (March 1, 1988): 483–97. http://dx.doi.org/10.1093/genetics/118.3.483.

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Abstract The neurogenic loci comprise a small group of genes which are required for proper division between the neural and epidermal pathways of differentiation within the neuroectoderm. Loss of neurogenic gene function results in the misrouting of prospective epidermal cells into neuroblasts. A molecular analysis of the neurogenic locus mastermind (mam) has been initiated through transposon tagging with P elements. Employing the Harwich strain as the source of P in a hybrid dysgenesis screen, 6000 chromosomes were tested for the production of lethal mam alleles and eight mutations were isolated. The mam region is the site of residence of a P element in Harwich which forms the focus of a chromosome breakage hotspot. Hybrid dysgenic induced mam alleles elicit cuticular and neural abnormalities typical of the neurogenic phenotype, and in five of the eight cases the mutants appear to retain a P element in the cytogenetic region (50CD) of mam. Utilizing P element sequence as probe, mam region genomic DNA was cloned and used to initiate a chromosome walk extending over 120 kb. The physical breakpoints associated with the hybrid dysgenic alleles fall within a 60-kb genomic segment, predicting this as the minimal size of the mam locus barring position effects. The locus contains a high density of repeated elements of two classes; opa (CAX)n and (dC-dA)n.(dG-dT)n. A preliminary study of the transcriptional activity of the mam region is presented.

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Jones, Katherine H., Jingchun Liu, and P. N. Adler. "Molecular Analysis of EMS-Induced frizzled Mutations in Drosophila melanogaster." Genetics 142, no. 1 (January 1, 1996): 205–15. http://dx.doi.org/10.1093/genetics/142.1.205.

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The frizzled (fz) gene of Drosophila is essential for the development of normal tissue polarity in the adult cuticle of Drosophila. In fz mutants the parallel array of hairs and bristles that decorate the cuticle is disrupted. Previous studies have shown that fz encodes a membrane protein with seven putative transmembrane domains, and that it has a complex role in the development of tissue polarity, as there exist both cell-autonomous and cell nonautonomous alleles. We have now examined a larger number of alleles and found that 15 of 19 alleles display cell nonautonomy. We have examined these and other alleles by Western blot analysis and found that most fz mutations result in altered amounts of Fz protein, and many also result in a Fz protein that migrates aberrantly in SDS-PAGE. We have sequenced a subset of these alleles. Cell nonautonomous fz alleles were found to be associated with mutations that altered amino acids in all regions of the Fz protein. Notably, the four cell-autonomous mutations were all in a proline residue located in the presumptive first cytoplasmic loop of the protein. We have also cloned and sequenced the fz gene from D. virilis. Conceptual translation of the D. virilis open reading frame indicates that the Fz protein is unusually well conserved. Indeed, in the putative cytoplasmic domains the Fz proteins of the two species are identical.

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Montell, Craig. "Drosophila sensory receptors—a set of molecular Swiss Army Knives." Genetics 217, no. 1 (January 1, 2021): 1–34. http://dx.doi.org/10.1093/genetics/iyaa011.

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Abstract Genetic approaches in the fruit fly, Drosophila melanogaster, have led to a major triumph in the field of sensory biology—the discovery of multiple large families of sensory receptors and channels. Some of these families, such as transient receptor potential channels, are conserved from animals ranging from worms to humans, while others, such as “gustatory receptors,” “olfactory receptors,” and “ionotropic receptors,” are restricted to invertebrates. Prior to the identification of sensory receptors in flies, it was widely assumed that these proteins function in just one modality such as vision, smell, taste, hearing, and somatosensation, which includes thermosensation, light, and noxious mechanical touch. By employing a vast combination of genetic, behavioral, electrophysiological, and other approaches in flies, a major concept to emerge is that many sensory receptors are multitaskers. The earliest example of this idea was the discovery that individual transient receptor potential channels function in multiple senses. It is now clear that multitasking is exhibited by other large receptor families including gustatory receptors, ionotropic receptors, epithelial Na+ channels (also referred to as Pickpockets), and even opsins, which were formerly thought to function exclusively as light sensors. Genetic characterizations of these Drosophila receptors and the neurons that express them also reveal the mechanisms through which flies can accurately differentiate between different stimuli even when they activate the same receptor, as well as mechanisms of adaptation, amplification, and sensory integration. The insights gleaned from studies in flies have been highly influential in directing investigations in many other animal models.

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Rizki, T. M., R. M. Rizki, and R. A. Bellotti. "Genetics of a Drosophila phenoloxidase." Molecular and General Genetics MGG 201, no. 1 (September 1985): 7–13. http://dx.doi.org/10.1007/bf00397978.

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Boettner, Benjamin, Phoebe Harjes, Satoshi Ishimaru, Michael Heke, Hong Qing Fan, Yi Qin, Linda Van Aelst, and Ulrike Gaul. "The AF-6 Homolog Canoe Acts as a Rap1 Effector During Dorsal Closure of the Drosophila Embryo." Genetics 165, no. 1 (September 1, 2003): 159–69. http://dx.doi.org/10.1093/genetics/165.1.159.

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Abstract Rap1 belongs to the highly conserved Ras subfamily of small GTPases. In Drosophila, Rap1 plays a critical role in many different morphogenetic processes, but the molecular mechanisms executing its function are unknown. Here, we demonstrate that Canoe (Cno), the Drosophila homolog of mammalian junctional protein AF-6, acts as an effector of Rap1 in vivo. Cno binds to the activated form of Rap1 in a yeast two-hybrid assay, the two molecules colocalize to the adherens junction, and they display very similar phenotypes in embryonic dorsal closure (DC), a process that relies on the elongation and migration of epithelial cell sheets. Genetic interaction experiments show that Rap1 and Cno act in the same molecular pathway during DC and that the function of both molecules in DC depends on their ability to interact. We further show that Rap1 acts upstream of Cno, but that Rap1, unlike Cno, is not involved in the stimulation of JNK pathway activity, indicating that Cno has both a Rap1-dependent and a Rap1-independent function in the DC process.

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Kubli, Eric. "Molecular mechanisms of suppression in Drosophila." Trends in Genetics 2 (January 1986): 204–9. http://dx.doi.org/10.1016/0168-9525(86)90231-3.

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Jones, W. K., and J. M. Rawls. "Genetic and molecular mapping of chromosome region 85A in Drosophila melanogaster." Genetics 120, no. 3 (November 1, 1988): 733–42. http://dx.doi.org/10.1093/genetics/120.3.733.

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Abstract Chromosome region 85A contains at least 12 genetic complementation groups, including the genes dhod, pink and hunchback. In order to better understand the organization of this chromosomal segment and to permit molecular studies of these genes, we have carried out a genetic analysis coupled with a chromosome walk to isolate the DNA containing these genes. Complementation tests with chromosomal deficiencies permitted unambiguous ordering of most of the complementation groups identified within the 85A region. Recombinant bacteriophage clones were isolated that collectively span over 120 kb of 85A DNA and these were used to produce a molecular map of the region. The breakpoint sites of a number of 85A chromosome rearrangements were localized on the molecular map, thereby delimiting regions of the DNA that contain the various genetic complementation groups.

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Hekmat-Scafe, Daria S., Robert L. Dorit, and John R. Carlson. "Molecular Evolution of Odorant-Binding Protein Genes OS-E and OS-F in Drosophila." Genetics 155, no. 1 (May 1, 2000): 117–27. http://dx.doi.org/10.1093/genetics/155.1.117.

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Abstract The Drosophila olfactory genes OS-E and OS-F are members of a family of genes that encode insect odorant-binding proteins (OBPs). OBPs are believed to transport hydrophobic odorants through the aqueous fluid within olfactory sensilla to the underlying receptor proteins. The recent discovery of a large family of olfactory receptor genes in Drosophila raises new questions about the function, diversity, regulation, and evolution of the OBP family. We have investigated the OS-E and OS-F genes in a variety of Drosophila species. These studies highlight potential regions of functional significance in the OS-E and OS-F proteins, which may include a region required for interaction with receptor proteins. Our results suggest that the two genes arose by an ancient gene duplication, and that in some lineages, one or the other gene has been lost. In D. virilis, the OS-F gene shows a different spatial pattern of expression than in D. melanogaster. One of the OS-F introns shows a striking degree of conservation between the two species, and we identify a putative regulatory sequence within this intron. Finally, a phylogenetic analysis places both OS-E and OS-F within a large family of insect OBPs and OBP-like proteins.

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Wines, D. R., and S. Henikoff. "Somatic instability of a Drosophila chromosome." Genetics 131, no. 3 (July 1, 1992): 683–91. http://dx.doi.org/10.1093/genetics/131.3.683.

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Abstract A mitotically unstable chromosome, detectable because of mosaic expression of marker genes, was generated by X-ray mutagenesis in Drosophila. Nondisjunction of this chromosome is evident in mitotic chromosome preparations, and premature sister chromatid separation is frequent. The mosaic phenotype is modified by genetic elements that are thought to alter chromatin structure. We hypothesize that the mitotic defects result from a breakpoint deep in the pericentric heterochromatin, within or very near to the DNA sequences essential for centromere function. This unique chromosome may provide a tool for the genetic and molecular dissection of a higher eukaryotic centromere.

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Inlow, Jennifer K., and Linda L. Restifo. "Molecular and Comparative Genetics of Mental Retardation." Genetics 166, no. 2 (February 1, 2004): 835–81. http://dx.doi.org/10.1093/genetics/166.2.835.

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Abstract Affecting 1-3% of the population, mental retardation (MR) poses significant challenges for clinicians and scientists. Understanding the biology of MR is complicated by the extraordinary heterogeneity of genetic MR disorders. Detailed analyses of &gt;1000 Online Mendelian Inheritance in Man (OMIM) database entries and literature searches through September 2003 revealed 282 molecularly identified MR genes. We estimate that hundreds more MR genes remain to be identified. A novel test, in which we distributed unmapped MR disorders proportionately across the autosomes, failed to eliminate the well-known X-chromosome overrepresentation of MR genes and candidate genes. This evidence argues against ascertainment bias as the main cause of the skewed distribution. On the basis of a synthesis of clinical and laboratory data, we developed a biological functions classification scheme for MR genes. Metabolic pathways, signaling pathways, and transcription are the most common functions, but numerous other aspects of neuronal and glial biology are controlled by MR genes as well. Using protein sequence and domain-organization comparisons, we found a striking conservation of MR genes and genetic pathways across the ∼700 million years that separate Homo sapiens and Drosophila melanogaster. Eighty-seven percent have one or more fruit fly homologs and 76% have at least one candidate functional ortholog. We propose that D. melanogaster can be used in a systematic manner to study MR and possibly to develop bioassays for therapeutic drug discovery. We selected 42 Drosophila orthologs as most likely to reveal molecular and cellular mechanisms of nervous system development or plasticity relevant to MR.

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Rossi, Fabrizio, Roberta Moschetti, Ruggiero Caizzi, Nicoletta Corradini, and Patrizio Dimitri. "Cytogenetic and Molecular Characterization of Heterochromatin Gene Models in Drosophila melanogaster." Genetics 175, no. 2 (November 16, 2006): 595–607. http://dx.doi.org/10.1534/genetics.106.065441.

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Bedford, Trevor, Ilan Wapinski, and Daniel L. Hartl. "Overdispersion of the Molecular Clock Varies Between Yeast, Drosophila and Mammals." Genetics 179, no. 2 (May 27, 2008): 977–84. http://dx.doi.org/10.1534/genetics.108.089185.

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