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1.
The X chromosome constitutes a unique genomic environment because it is present in one copy in males, but two copies in females. This simple fact has motivated several theoretical predictions with respect to how standing genetic variation on the X chromosome should differ from the autosomes. Unmasked expression of deleterious mutations in males and a lower census size are expected to reduce variation, while allelic variants with sexually antagonistic effects, and potentially those with a sex-specific effect, could accumulate on the X chromosome and contribute to increased genetic variation. In addition, incomplete dosage compensation of the X chromosome could potentially dampen the male-specific effects of random mutations, and promote the accumulation of X-linked alleles with sexually dimorphic phenotypic effects. Here we test both the amount and the type of genetic variation on the X chromosome within a population of Drosophila melanogaster, by comparing the proportion of X linked and autosomal trans-regulatory SNPs with a sexually concordant and discordant effect on gene expression. We find that the X chromosome is depleted for SNPs with a sexually concordant effect, but hosts comparatively more SNPs with a sexually discordant effect. Interestingly, the contrasting results for SNPs with sexually concordant and discordant effects are driven by SNPs with a larger influence on expression in females than expression in males. Furthermore, the distribution of these SNPs is shifted towards regions where dosage compensation is predicted to be less complete. These results suggest that intrinsic properties of dosage compensation influence either the accumulation of different types of trans-factors and/or their propensity to accumulate mutations. Our findings document a potential mechanistic basis for sex-specific genetic variation, and identify the X as a reservoir for sexually dimorphic phenotypic variation. These results have general implications for X chromosome evolution, as well as the genetic basis of sex-specific evolutionary change. 相似文献
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O. G. Cherednichenko Z. M. Biyasheva N. B. Akhmatullina 《Russian Journal of Genetics》2001,37(7):748-753
Mutagenic potential of the influenza virus was evaluated. Based on its capacity of inducing recessive lethal mutations in the X chromosome of Drosophila melanogaster, the influenza virus can be classified as a moderate-activity mutagen. Its mutagenicity does not depend on ability to reproduce in the cell system. This virus was shown to disrupt formation of the wing, particularly wing vein M1 + 2. Cytogenetic examination of polytene X chromosomes bearing recessive lethal mutations in Drosophilasalivary glands did not reveal chromosome rearrangements. These lethals are assumed to be small deletions or point mutations. The determination of the lethal activity stage of these mutations showed that they disrupt the expression of genes functioning at various developmental stages of Drosophila.Two of them were conditionally lethal (temperature-sensitive). Two of 15 mutations analyzed were mapped to region 2B9-10–3C10-11. 相似文献
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Aloha Hannah-Alava 《Molecular & general genetics : MGG》1971,113(3):191-203
Summary The results from cytological identification of 125 radiation-induced specificlocus mutations revealed that the relative frequency of nucleolus-associated rearrangements could be increased substantially by selection of specific types of position-mutations for cytological analysis.One of the five nucleolus-involved rearrangements investigated was an inversion, In(1)lz
sB, and four were deletion-insertions: Tp(1)ct
6a1, Tp(1)lz
491, Tp(1)lz
144 and Dp(1;3)in
61j2.The cytomorphology of the transposed nucleolus and associated bands was easier to resolve in the salivary gland chromosomes of the rearrangements than when the nucleolus was in its normal position in the proximal region of the X-chromosome. However, the extent of the NO and adjacent chromatin involved in the transposition could not be positively delimited because of the tendency for a variegation-type alteration in the morphology of the bands adjacent to the transposed nucleolus.This investigation was supported in part by U.S. Public Health Service Research Grant, GM 15009, and in part by a grant from the Finnish National Research Council for Sciences. 相似文献
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Koen J. T. Venken Ellen Popodi Stacy L. Holtzman Karen L. Schulze Soo Park Joseph W. Carlson Roger A. Hoskins Hugo J. Bellen Thomas C. Kaufman 《Genetics》2010,186(4):1111-1125
We describe a molecularly defined duplication kit for the X chromosome of Drosophila melanogaster. A set of 408 overlapping P[acman] BAC clones was used to create small duplications (average length 88 kb) covering the 22-Mb sequenced portion of the chromosome. The BAC clones were inserted into an attP docking site on chromosome 3L using ΦC31 integrase, allowing direct comparison of different transgenes. The insertions complement 92% of the essential and viable mutations and deletions tested, demonstrating that almost all Drosophila genes are compact and that the current annotations of the genome are reasonably accurate. Moreover, almost all genes are tolerated at twice the normal dosage. Finally, we more precisely mapped two regions at which duplications cause diplo-lethality in males. This collection comprises the first molecularly defined duplication set to cover a whole chromosome in a multicellular organism. The work presented removes a long-standing barrier to genetic analysis of the Drosophila X chromosome, will greatly facilitate functional assays of X-linked genes in vivo, and provides a model for functional analyses of entire chromosomes in other species.THE X chromosome of Drosophila melanogaster contains ∼2300 protein-coding genes or ∼15% of such genes in the genome. It contains 22 Mb of euchromatic DNA (Adams et al. 2000). About one-third of these genes are predicted to be mutable to a phenotype that can be scored, e.g., lethality, sterility, or abnormal behavior (Peter et al. 2002). However, most molecularly recognized X-linked genes have not been associated with mutations or studied in any detail (http://flybase.org) (Drysdale 2008). Indeed, one hallmark of the X chromosome in D. melanogaster and many other species is that it is haploid in males. In addition, the presence of one copy of the X in an otherwise diploid animal leads to the phenomenon of dosage compensation, a process that essentially doubles the expression of X-linked genes in Drosophila males (Gelbart and Kuroda 2009).The presence of a single X chromosome in males facilitates screens for behavioral or visible mutant phenotypes in the hemizygous male progeny of a single-generation cross. For this reason, the X chromosome has been well saturated for viable mutations. However, many of these mutations have not been mapped since existing methods are tedious. Moreover, mutations in essential genes and genes required for male fertility cannot be propagated and genetically characterized unless they are complemented with a duplication maintained in the male. Hence, the X chromosome has been significantly less studied than the autosomes for mutations in essential and male fertility genes. For many of those mutations, the genes associated with these phenotypes have been elusive due to the lack of appropriate genetic reagents. Thus, X-linked genes in critical developmental and regulatory pathways are underrepresented in reported analyses as compared to similar classes of genes on the autosomes.Mutations in essential and male fertility genes on the X chromosome can be mapped using a variety of techniques. One approach is to rely on recombination in females and perform meiotic mapping against visible markers (Lindsley and Zimm 1992), P-element insertions (Zhai et al. 2003), or SNPs (Berger et al. 2001; Hoskins et al. 2001; Martin et al. 2001; Nairz et al. 2002; Chen et al. 2008), all of which are labor-intensive strategies or require specialized infrastructure. An alternative is complementation mapping using deficiencies, which requires only a single cross. This approach is possible for viable mutations but not for X-linked lethal and sterile mutations since those cannot be propagated through males. Instead, complementation rescue tests need to be carried out using a segregating duplication, e.g., an X chromosome fragment on the Y chromosome [Dp(1;Y)], an autosome [Dp(1;A)], or a free duplication [Dp(1;f)] (Lindsley and Zimm 1992). Currently, duplications that encompass ∼90% of the X chromosome are available. Only three cytological regions at 13A–13F (∼1 Mb), 16D7–16F4 (∼0.3 Mb), and 18A–18F (∼0.8 Mb) are not covered. Unfortunately, these duplications are typically very large (∼1–1.5 Mb) (http://flybase.org/) (Drysdale 2008), limiting their utility for fine mapping. Moreover, most available duplications were isolated following X-ray mutagenesis, and their breakpoints are poorly defined.Hence, a complete set of small molecularly defined duplications of the X chromosome would be extremely useful for identifying mutations in essential and male fertility genes and for fine-scale mapping of any mutation, including recessive viable mutations. In addition to promoting new genetic screens, a duplication set would allow one to map and assess the numerous, poorly characterized X-linked lethal mutants. Moreover, if molecularly defined genomic DNA clones are used to create the duplication set, then epitope tagging using recombineering would permit determination of expression patterns of genes included in the duplications (Venken et al. 2008, 2009; Ejsmont et al. 2009). Finally, such defined duplications would allow one to carry out structure–function analyses of genes through recombineering by introducing point mutations and small deletions into a gene of interest at unprecedented speed (Sharan et al. 2009).Previously, we created the P[acman] (P/ΦC31 artificial chromosome for manipulation) transgenesis platform (Venken and Bellen 2005, 2007; Venken et al. 2006) for retrieval and manipulation of large DNA fragments in a conditionally amplifiable BAC (Wild et al. 2002). Genomic clones inserted into this vector can be subjected to recombineering (Sharan et al. 2009) and used for transformation of these fragments (up to at least 146 kb) into the genome of flies that carry a defined attP docking site using the ΦC31 integrase system (Groth et al. 2004; Venken et al. 2006; Bischof et al. 2007; Markstein et al. 2008). In a next step, we constructed two genomic BAC libraries, one with an average insert size of 21 kb (CHORI-322) and another with an average insert size of 83 kb (CHORI-321) (Venken et al. 2009). These BAC libraries were end-sequenced and mapped onto the genome sequence and are publicly available (http://pacmanfly.org) and distributed (http://bacpac.chori.org/). Here we bring these resources to a next level: BAC TransgeneOmics (Poser et al. 2008) of an entire chromosome in vivo. The 8.2-fold coverage of the X chromosome in mapped clones from the CHORI-321 library allowed us to select a tiled path of overlapping BACs containing almost all of the annotated genes on this chromosome. Here we describe the creation of the first set of molecularly defined duplications covering an entire chromosome of a multicellular organism, and we illustrate its utility for X-chromosome genetics in several experimental paradigms. 相似文献
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Homologous recombination affects myriad aspects of genome evolution, from standing levels of nucleotide diversity to the efficacy of natural selection. Rates of crossing over show marked variability at all scales surveyed, including species-, population-, and individual-level differences. Even within genomes, crossovers are nonrandomly distributed in a wide diversity of taxa. Although intra- and intergenomic heterogeneities in crossover distribution have been documented in Drosophila, the scale and degree of crossover rate heterogeneity remain unclear. In addition, the genetic features mediating this heterogeneity are unknown. Here we quantify fine-scale heterogeneity in crossover distribution in a 2.1-Mb region of the Drosophila melanogaster X chromosome by localizing crossover breakpoints in 2500 individuals, each containing a single crossover in this specific X chromosome region. We show 90-fold variation in rates of crossing over at a 5-kb scale, place this variation in the context of several aspects of genome evolution, and identify several genetic features associated with crossover rates. Our results shed new light on the scale and magnitude of crossover rate heterogeneity in D. melanogaster and highlight potential features mediating this heterogeneity. 相似文献
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The Notch locus of Drosophila melanogaster 总被引:48,自引:0,他引:48
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Ten laboratory stocks of Drosophila melanogaster initiated from females collected in different localities in India were analysed for chromosome inversions. Six inversions were found to be present, three in 2L, one in 2R, one in 3L and one in 3R. Out of these six inversions, three are new and are being reported for the first time. Furthermore, this is the first report of inversion polymorphism in Indian D. melanogaster. The persistence of inversion polymorphism in our laboratory stocks of D. melanogaster which were maintained for more than one year under laboratory conditions, suggests some heterotic advantage of inversion heterozygotes. 相似文献
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The Notch gene encodes a receptor protein that is involved in many processes during development. Its best understood role is during neurogenesis in a process called ``lateral inhibition.' However, it has been proposed that Notch also has a role in defining the proneural clusters in the first place. This raises the possibility that the Notch protein is acting as a multifunctional receptor. To test this hypothesis, we have carried out a genetic analysis of molecularly characterized Notch alleles to identify alleles that affect only one of the two proposed functions. Here we present evidence that Notch alleles can be identified that appear to affect the function of Notch during either lateral inhibition or the definition of proneural clusters. In addition our results indicate that there may be discrete regions of the Notch protein required for each function. 相似文献
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The molecular genetics of the Notch locus in Drosophila melanogaster 总被引:13,自引:0,他引:13
B G Grimwade M A Muskavitch W J Welshons B Yedvobnick S Artavanis-Tsakonas 《Developmental biology》1985,107(2):503-519
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The determination of segment identity in Drosophila melanogaster appears to be controlled by a small number of genes. In order to identity new components in the process, we have systematically screened the autosomal complement for loci that show a dosage-dependent interaction with mutations in previously characterized genes thought to be important in the determination of segment identity. The dominant homoeotic phenotype of mutations at four loci involved in thoracic leg determination (Pc, Pcl, Antp and Scr) were quantitated in flies bearing a series of synthetic duplications covering more than 99% of the autosomal complement. Twelve regions were identified that when present in three wild-type copies strongly enhanced or suppressed the phenotype of mutations at one or more of the four homoeotic loci examined. The effects of five of these regions appear to correspond to previously described homoeotic loci; the effects of the remaining seven appear to identify new loci involved in the determination of segment identity. 相似文献
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Donald A. Gailey Deborah L. Bordne Ana Maria Vallés Jeffrey C. Hall Kalpana White 《Genetics》1987,115(2):305-311
An unstable Ring-X chromosome, Ddc+- Ring-X carrying a cloned Dopa decarboxylase (Ddc) encoding segment was constructed. The construction involved a double recombination event between the unstable Ring-X, R(1)wvC and a Rod-X chromosome which contained a P-element mediated Ddc + insert. The resulting Ddc+-Ring-X chromosome behaves similarly to the parent chromosome with respect to somatic instability. The Ddc+-Ring-X chromosome was used to generate Ddc mosaics. Analyses of Ddc mosaics revealed that while there was no absolute requirement for the Ddc + expression in either the epidermis or the nervous system, very large mutant clones did affect the viability of the mosaic. 相似文献