Showing papers on "Dosage compensation published in 1975"

Control of Chromosome Inactivation

Abstract: While it is generally believed that eukaryotes must have regulatory mechanisms similar to those of prokaryotes to switch genes on and off as required throughout development (1-5), more clearly established is a different order of genetic regulation, one by which whole chromosomes cr chromosome regions become genetically active and potentially capable of transcription, or seemingly totally genetically inactive and unable to transcribe. The most widely known example is probably that of the mammalian X chromosome (6, 7). Only one X is active in the somatic cells of females, and this system serves as a dosage compensation mechanism, reducing the effective X chromosome dosage in the XX female to that of the XY male. In marsupials, at least in blood cells, the inactive X is always the X derived from the father (8-10), but in eutherian mammals either X may be the inactive one, the choice being made in each cell at an early stage of embryonic development and being fixed in that each descendant cell line follows the original decision and has the same X inactivated. Chromosomal inactivation events are also well documented in species of mealy bugs (11, 12); in Sciara (13, 14), a complex pattern of chromosome loss rather than chromosome inactivation occurs and may represent a more extreme form of the same mecha­ nism. This paper is concerned with this order of genetic regulation and particularly with the behavior of the mammalian X chromosome. Much information is available that establishes the basic concepts of the inactive-X hypothesis beyond all reasonable doubt [for extensive reviews, see Lyon (7,15-19)). In this paper, however, only those aspects of the system that have some bearing on possible control mechanisms are discussed.

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

Abstract: 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.

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.

Abstract: 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.

Sex-linked isozymes and sex chromosome evolution and inactivation in kangaroos

Abstract: The structural genes for the enzymes glucose-6-phosphate dehydrogenase (G6PD) and phosphoglycerate kinase (PGK A ) are sex-linked in marsupials. This accords with Ohno's thesis of the conservative nature of the X-linkage group in mammals, since those two genes are also sex-linked in Man. The data on the inheritance of isozymic forms of these enzymes and the phenotypes of females heterozygous for them suggest that the cells and tissues of kangaroos may be divided into at least two kinds. One kind, represented by the blood, has dosage compensation achieved by paternal X-inactivation . The other kind, represented by primary uncloned cultures of fibroblasts, may have both chromosomes active though whether within the same cell is not known. The G6PD patterns of heterozygotes seemingly have interaction products, a result which is compatible either with activity of both alleles within the same cell or transfer of gene product between cells within a mixture of cells with contrasting types active. PGK A patterns of lysates of primary uncloned cultures of fibroblasts and also muscle homogenates, both derived from heterozygotes, show expression of both isozymes with the maternally derived one always predominant.