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At least 19 recordsLinked to original sources
PubMed1992

Dosage compensation of the copia retrotransposon in Drosophila melanogaster.

Dosage compensation in Drosophila has been studied at the steady state RNA level for several single-copy genes; however, an important point is addressed by analyzing a repetitive, transposable element for dosage compensation. The two issues of gene-specific cis control and genomic position can be studied by determining the extent of dosage compensation of a transposable element at different chromosomal locations. To determine whether the multicopy copia transposable element can dosage compensate, we used the X-linked white-apricot (wa) mutation in which a copia element is present. The extent of dosage compensation was determined for the white and copia promoters in larvae and adults in two different genomic locations of the wa allele. We conclude that copia is able to dosage compensate, and that the white promoter and the copia promoter are not coordinate in their dosage compensation abilities when assayed under these various conditions. Thus, two transcriptional units, one within the other, both of which are able to dosage compensate, do so differently in response to developmental stage and genomic position.

Animals↗
PubMed1978

Gene dosage compensation and the evolution of sex chromosomes.

Dosage compensation is a mechanism by means of which the activity of X-linked or Z-linked genes is made equal in the two sexes of organisms with an XX compared to XY or ZZ compared to ZW basis of sex determination. In mammals, compensation is achieved by the inactivation of one X chromosome in somatic cells of females. In Drosophila, compensation does not involve inactivation. The two X chromosomes in females as well as the single X in males are regulated, and individual genes are thought to respond independently to the regulatory mechanism. It is proposed that in both groups of organisms the evolution of heteromorphic sex chromosomes was gradual and occurred as the direct result of the evolution of dosage compensation rather than the reverse.

Alleles↗
PubMed1978

Incomplete dosage compensation in an evolving Drosophila sex chromosome.

Cellular autoradiography was used to measure relative rates of chromosomal RNA synthesis and to examine the regulatory phenomenon of X-linked dosage compensation in Drosophila miranda, a species containing two distinct, nonhomologous X chromosomes (X1 and X2). The X1 chromosome was found to be dosage-compensated, since the rate of RNA synthesis along the single X1 chromosome in males equaled that of both X1 chromosomes in females. Unlike other sex chromosomes that have been studied, the more recently evolved X2 heterochromosome exhibited regional differences in transcriptional activity when males and females were compared. The distal 10% of the X2 was not dosage-compensated, whereas the majority of an interior segment, representing 30% of the X2 chromosome's length, was found to be dosage-compensated. Our data are consistent with the idea that the evolution of X2 dosage compensation has paralleled the differentiation of the X2 sex chromosome. In addition, gene rearrangement seems to have accompanied the acquisition of a dosage-compensory mechanism in the X2.

Animals↗
PubMed2026

Mixed Evidence that Dosage Sensitive Genes Drive Global Dosage Compensation in Flour Beetles.

Heteromorphic sex chromosomes create inherent gene dosage differences between males and females because one sex carries a single copy of the X chromosome while the other carries two. Many species have evolved mechanisms that equalize X-linked gene expression between the sexes and, in some cases, restore ancestral autosomal levels, a process known as dosage compensation. Although chromosome-wide compensation is common in male heterogametic (XY) insects, regulatory outcomes vary across taxa and sex chromosome systems, leaving the evolutionary forces shaping sex chromosome regulation unresolved. One hypothesis proposes that the extent to which genes are sensitive to changes in gene dose determines whether complete compensation evolves. We tested predictions of this insensitive sex chromosome hypothesis (ISCH) across five flour beetle species using comparative transcriptomics and genome-wide RNAi-derived measures of gene-by-gene sensitivity. Including an X-autosome fusion in Tribolium confusum allowed direct assessment of expression evolution following a transition from a diploid autosome to a hemizygous Neo-X. Across all five species, we detect complete chromosome-wide dosage compensation and balance between the sexes in somatic tissues, including the Neo-X region. Consistent with ISCH predictions, neither the ancestral Shared-X nor the Neo-X is depleted of genes that are sensitive to RNAi-based expression disruption. However, contrary to expectations, at the level of individual genes, we find little evidence that more sensitive genes exhibit reduced expression divergence. These results suggest that chromosome-wide compensation can be maintained by global regulatory mechanisms that persist through sex chromosome turnover, even when gene-by-gene constraints are weak. Understanding the molecular basis of these mechanisms remains a central challenge in sex chromosome evolution.

Animals↗
PubMed1975

Regulation of gene activity by dosage compensation at the chromosomal level in drosophila.

Two models of dosage compensation have been tested by the measurement of G6PD and 6PGD enzymatic specific activities in flies hyperploid for regions of the X chromosome. Females duplicated for the proximal half of the X chromosomes (2 1/2 X's) have an increased level of G6PD and a normal level of 6PGD. Females duplicated for the distal half of the X chromosome (2 1/2 X's) have a normal level of G6PD and an increased level of 6PGD. Males bearing duplications of various segments of the X chromosome show control levels of G6PD and 6PGD, except where the duplicated region includes the structural gene for G6PD or 6PGD. These results fail to provide evidence for either the presence of discrete X-linked compensator (regulator) genes reducing the activity of other X-linked genes, or for a factor in limiting supply necessary for the transcription of all the genes on the X chromosome. Superfemales (3 X chromosomes) have the same G6PD and 6PGD activity levels as their diploid sisters. It would appear that the regulation of gene activity by dosage compensation is a chromosomal phenomenon in that the level of activity per gene copy for loci on the X chromosome is modulated in a stepwise fashion according to the total number of X chromosomes present.

Aneuploidy↗
PubMed1977

The nature of quantitative genetic variation in Drosophila. III. Mechanism of dosage compensation for sex-linked abdominal bristle polygenes.

Seventeen lines, each homozygous for a different X chromosome but all with a common autosomal genetic blackground, were constructed and assayed for abdominal bristle number to determine whether dosage compensation operates for sex-linked genes affecting this character. --The regression coefficient of male mean on female mean using a logarithmic scale was 0.90 +/- 0.13 and the genetic regression coefficient 0.92, neither differing significantly from unity. The genetic components of variance in males and females were also very similar (0.000234 or 0.000228, respectively). These results indicate that dosage compensation is complete (or nearly so) for sex-linked genes affecting this character. The bristle scores of females did not differ in reciprocal crosses between these lines, thus dosage compensation does not operate by paternal X inactivation. --The question of an adequate scale for abdominal bristle number had to be examined during the study. A logarithmic scale appeared to be adequate for both genotypic and environmental differences.

Animals↗
PubMed2025

Chromatin Landscape Is Associated With Sex-Biased Expression and Drosophila-Like Dosage Compensation of the Z Chromosome in Artemia franciscana.

The males and females of the brine shrimp Artemia franciscana are highly dimorphic, and this dimorphism is associated with substantial sex-biased gene expression in heads and gonads. How these sex-specific patterns of expression are regulated at the molecular level is unknown. A. franciscana also has differentiated ZW sex chromosomes, with complete dosage compensation, but the molecular mechanism through which compensation is achieved is unknown. Here, we conducted CUT&TAG assays targeting 7 post-translational histone modifications (H3K27me3, H3K9me2, H3K9me3, H3K36me3, H3K27ac, H3K4me3, and H4K16ac) in heads and gonads of A. franciscana, allowing us to divide the genome into 12 chromatin states. We further defined functional chromatin signatures for all genes, which were correlated with transcript level abundances. Differences in the occupancy of the profiled epigenetic marks between sexes were associated with differential gene expression between males and females. Finally, we found a significant enrichment of the permissive H4K16ac histone mark in the Z-specific region in both tissues of females but not males, supporting the role of this histone mark in mediating dosage compensation of the Z chromosome.

Animals↗
PubMed1975

Dosage compensation and ontogenic expression of suppressed and transformed Vermilion flies in Drosophila.

A spectrofluorometric assay system for tryptophan oxygenase was used to compare dosage compensation properties and ontogenic expression of suppressed, "transformed," and wild-type vermilion flies. The results indicate that, although different stocks showed different levels of oxygenase activity, all showed dosage compensation properties. The ontogenic expression of tryptophan oxygenase was observed to be different in the various genotypes. Whereas suppressed vermilion resembled wild type in its pattern, the ontogenic profiles of "transformed" flies were different.

Alleles↗
PubMed1977

Evidence for dosage compensation in parthenogenetic Hymenoptera.

Amounts of DNA-Feulgen staining in individual somatic nuclei and mature sperm of the parthenogenetic wasps, Habrobracon juglandis, H. serinopae, and Mormoniella vitripennis, were determined with a scanning microdensitometer. The haploid genome for both species of Habrobracon was estimated to be 0.15-0.16 X 10-(12) gDNA, corresponding to a molecular weight of roughly 10 X10(10) daltons. The haploid genome of M. vitripennis is approximately twice this value, 0.33-0.34 X 10-(12) g, or about 20X10(10) daltons. Measurements made on dividing nuclei from syncytial preblastoderm embryos of H. juglandis and M. viripennis showed that the chromosomes of impaternate males were present in the haploid number and contained the C amount of DNA; whereas nuclei from female preblastoderm embryos contained the diploid number of chromosomes and the 2C amount of DNA. However, hemocyte and brain cell nuclei from either male or female adult wasps contained 2C and 4C amounts of DNA. Both sexes also showed equivalent levels of polyploidy (8C, 16C, or 32C) in Malpighian tubule nuclei. Therefore, in these parthenogenetic species,, a mechanism must exist the compensates during later development for the initial two-fold difference in the chromatin content of somatic nuclei in haploid male and diploid female embryos. Hemocytes from impaternate Mormoniella diploid males and triploid females contain the 2C and 3C amounts of DNA, respectively Therefore dosage compensation involves an additional cycle of DNA replication only in hapoid cells, and it insures that a certain minimum quantity of DNA is received by each somatic cell.

Animals↗
PubMed1978

Model for evolution of Y chromosomes and dosage compensation.

Some difficulties with the classical model for the evolution of a genetically invert Y chromosome are discussed. An alternative model is proposed, which is based on the principle of Mullers ratchet; this involves the accumulation of chromosomes bearing deleterious mutant genes in a finite population in the absence of crossing-over. This process would result in the gradual increase, with time, in the number of mutant loci carried in an average Y chromosome, although the frequency of individual deleterious alleles at most loci remains low. It is shown that this creates a selection pressure for differentially increasing the activity of the X chromosome in heterogametic individuals at the expense of that of the Y, leading eventually to a genetically inert Y chromosome and to the evolution of dosage compensation.

Alleles↗
PubMed2025

A tumorigenesis threshold for endogenous Myc revealed by dosage-compensation for Myc-haploinsufficiency in the absence of p53.

The MYC proto-oncogene is crucial for neoplasia in most tumors. Overexpressed, oncogenic MYC amplifies the flux through most major processes but does not specify a unique carcinogenic pathway. This "amplifier" model suggests that MYC must exceed an expression threshold to become oncogenic. We designed a genetic test of this model, using the mouse Trp53 null mutant (p53KO) as a highly robust tumor generator to examine the effect of a modest change in the endogenous Myc level (Myc +/-). Strikingly, tumor-free survival is greatly extended in p53KO mice with haploid Myc gene-dosage, yet in the tumors that do develop (mainly hemangiosarcomas and thymic lymphomas), their Myc deficit has been invariably compensated either by increasing Myc genomic dosage (hemangiosarcomas) or expression (lymphomas). Furthermore, acutely halving the endogenous Myc gene-dosage in established tumor allografts curtails growth rates. These results indicate that even an incremental reduction of MYC activity can be salutary in cancer and that one of the major tumor suppressor functions of p53 derives from its ability to prevent MYC overexpression. Myc generates acute DNA damage by several mechanisms and accordingly, p53's anti-Myc function may be inextricably linked to its role in genome integrity surveillance.

Myc haplo-insufficiency↗
PubMed1975

Chromosomal basis of dosage compensation in Drosophila VIII. Faster replication and hyperactivity of both arms of the X-chromosome in males of Drosophila pseudoobscura and their possible significance.

3H-thymidine and 3H-uridine labeling patterns of the X-chromosome arms of Drosophila pseudoobscura have been examined autoradiographically. Results show that in all phases of replication, namely, initial, middle and terminal, both arms of the X-chromosome in the male are advanced by one or two steps of 3H-thymidine labeling in comparison with the autosomes, and both arms in the female show more or less similar labeling profile as the autosomes. Both the arms in the male show pale stainability and enlarged width ratio, as reported in other species. The 3H-uridine labeling patterns also reveal that both arms in the male incorporate twice as much precursor as the individual X in the female. Results, therefore, suggest that both arms of the X in D. pseudoobscura are faster replicating and hyperactive in the male, although it is considered that XL is homologous to the X and XR to part of the third chromosome of D. melanogaster.

Animals↗
PubMed1977

Chromosomal basis of dosage compensation in Drosophila. IX. Cellular autonomy of the faster replication of the X chromosome in haplo-X cells of Drosophila melanogaster and synchronous initiation.

[(3)H]Thymidine labeling patterns have been examined in gynandric mosaic salivary glands of drosophila melanogaster. The Ring-X stock, R(1) w(ve)/In(1)dl 49, l (1) J1 y w lz(s), was used for this purpose. 365 labeled XX2A and 40 labeled XO2A nuclei were obtained from a total of 624 nuclei in nine pairs of mosaic salivary glands. It was observed that in all but those nuclei which had DD, 1C, and 2C patterns, the X chromosome of the XO2A nuclei always had fewer sites labeled than the X chromosomes of the XX2A nuclei, for a given pattern of the autosomes in either sex. Such asynchronous labeling of the X chromosome in the XO2A (male) nuclei was observed regardless of the proportion of the XO2A cells (2.0-73.7 percent), in the mosaic glands. Moreover, while the frequency of [(3)H]thymidine labeling for all of the 39 replicating units except the two late replicating sites (3C and 11A) in the X chromosome of the XO2A nuclei, was consistently lower than in the X chromosome of the XX2A nuclei, the mean number of grains on the X chromosome was relatively (to autosomes) similar in both XX2A and XO2A cells. The results, therefore, suggest that, as in XY2A larval glands, the X chromosome in the XO2A cells also completes the replication earlier than autosomes and that the XO2A nuclei show cellular autonomy with respect to the early replication of the X chromosome, like its counterpart, RNA transcription. Absence of the asynchrony during the initial phase (DD-2C) further completes the replication earlier but that the rate of replication of its DNA is possibly faster, and (b) that there might be a common regulation with respect to the initiation of replication of different chromosomes in a genome.

Animals↗