Showing papers on "Dosage compensation published in 1982"

Genetic homology and crossing over in the X and Y chromosomes of Mammals.

Abstract: The "X-Y crossover model" described in this paper postulates the (1) the pairing observed between the X and the Y chromosome at zygotene is a consequence of genetic homology, (2) there is a single obligatory crossover between the X and Y pacing segments, and (3) the segment of the X which pairs with the Y is protected from subsequent inactivation. Genes distal to the proposed crossover ("pseudoautosomal genes") will appear to be autosomally inherited because they will be transmitted to both male and female offspring. Some criteria for identifying pseudoautosomal genes are outlined. The existence of a single obligatory crossover between the X and Y of the mouse is strongly supported by a recent demonstration that the sex-reversing mutation Sxr, which is passed equally to XX and XY offspring by male carriers, is transmitted on the sex chromosomes. Pseudoautosomally inherited genes may also be responsible for XX sex reversal in goats and familial XX sex reversal in man.

X-Autosome translocations: Cytogenetic characteristics and their consequences

Abstract: To define the principal characteristics of X-autosome translocations, the authors present a study of 105 cases, five of which are personal observations. The autosomal pairs 15, 21, and 22 are affected by t(X-Aut) more often than would be expected. The distribution of breakpoints on the X chromosome does not differ significantly from the expected distribution. The analysis of different patterns of inactivation seems to confirm that the inactivation could occur at random, but would be followed by a cellular selection favoring the better genetic balance. An estimate of the incidence of t(X-Aut) is proposed, based upon the conclusions that only one chromosome is susceptible to translocation in meiosis in both males and females and that all affected men will be sterile, as will be 50% of women.

A sex-linked enzyme in birds—Z-chromosome conservation but no dosage compensation

Abstract: In birds, the female is the heterogametic sex and the sex-determining system is referred to as ZZ/ZW. In mammals the male is heterogametic, and the sex-determining system is referred to as XX/XY. The mammalian X chromosome appears to have been conserved largely intact during evolution. Thus the structural gene loci for glucose-6-phosphate de-hydrogenase, phosphoglycerate kinase, α-galactosidase and hypoxanthine–guanine phosphoribosyltransferase are situated on the X chromosome of a wide variety of mammals. In addition, mammals show ‘dosage compensation’; that is, although females possess two doses of each X-linked gene while males possess only one, females produce the same level of gene product as males. In birds, cytological studies and data on sex-linked morphological mutants suggest that1 the Z chromosomes of all birds are homologous, and that buds do not show dosage compensation for sex-linked genes. Ultimate proof of these hypotheses requires the discovery of proteins whose structural gene loci are encoded by the Z chromosome of birds1, none of which has previously been found. Here we report that the cytoplasmic isozyme of aconitase is Z-linked in the guinea fowl and probably Z-linked in the domestic fowl, house sparrow and two species of cockatoos, thereby providing evidence for Z-chromosome homology in birds. We also show that there is an apparent lack of dosage compensation for cytoplasmic aconitase in the domestic fowl, house sparrow and spotted turtledove.

Transformation with DNA from 5-azacytidine-reactivated X chromosomes

Abstract: It has been shown that 5-azacytidine (5-Aza-Cyd) can reactivate genes on the inactive human X chromosome. It is assumed that the 5-Aza-Cyd acts by causing demethylation of the DNA at specific sites, but this cannot be demonstrated directly without a cloned probe. Instead, we have utilized the technique of DNA-mediated transformation to show that the 5-Aza-Cyd-induced reactivation occurs at the DNA level. DNAs from various mouse-human or hamster-human hybrid cell lines, deficient for mouse or hamster hypoxanthine phosphoribosyltransferase (HPRT, EC 2.4.2.8) and varying in whether they contained either an active or inactive human X chromosome, were used in transformation of HPRT- cells. DNA from the active human X chromosome-containing cell lines yielded HPRT+ transformants, whereas DNA from the inactive X chromosome-containing cells lines did not. The inactive X chromosomal DNA was able to transform thymidine kinase-deficient mouse cells, indicating that the DNA solution was normal. These results confirm that inactivation of the X chromosome involves a DNA modification. Furthermore, DNAs from three cell lines with a 5-Aza-Cyd-reactivated X chromosome also transform HPRT- cells, demonstrating that the 5-Aza-Cyd has altered the DNA structure and supporting the idea that methylation plays a role in X chromosome inactivation.

Pairing of X and Y chromosomes, non-inactivation of X-linked genes, and the maleness factor.

Abstract: In this paper observations are summarized and speculations discussed, and it is suggested that some loci on the distal short arm of the X chromosome (Xp) are not randomly inactivated in the female, because they are within the proximal part of the pairing segment between Xp and Yp. This peculiarity of gene expression may be a remnant of the evolutionary history of the sex chromosomes, the pairing segment of which may involve at least 27% of Xp and 95% of Yp. Crossing over seems to occur mostly in the terminal third of the X/Y pairing segment. However, crossing-over inhibition control may lapse, or may be somewhat variable, within the pairing segment, so that some loci on the X and Y (e.g. Xg. H-Y, STS, and perhaps others) might cross over with a variable frequency which is proportional to their distances from the telomeres of the short arms. It is postulated that the DNA of the pairing segment is composed in a way which may also permit unequal crossing over to occur between the X and the Y, thereby giving rise to exceptions to X-or Y-linked inheritance. The peculiarities of behaviour and the position of other loci on the sex chromosomes are also discussed briefly.

Autosomal dosage compensation Drosophila melanogaster strains trisomic for the left arm of chromosome 2.

Abstract: Drosophila melanogaster individuals trisomic for an entire chromosome arm can survive to late stages of pupal development. We have examined the levels of five enzymes whose structural genes are located on the left arm of chromosome 2 both in trisomy 2L and in diploid strains. In trisomies, three distally mapping loci showed compensated levels of expression close to that observed in the diploid strains. Analysis of electrophoretic variants of a compensated locus revealed that all three alleles are active in trisomies. The two proximally located loci displayed dose-dependent levels of expression. Therefore, at the level of the individual gene, autosomal compensation appears to be an all-or-none phenomenon. Furthermore, the compensatory response may be regionally distributed along the chromosome arm. The presence of both autosomal and sex-linked dosage compensation prompts us to speculate that there phenomenon are similar homeostatic mechanisms that modulate gene expression both in euploid and aneuploid genomes.

Cytogenetics of South American Akodont Rodents (Cricetidae)

Abstract: Akodon azarae (Rodentia Cricetidae) has a sex chromosome polymorphism which gives rise to XX females and females with a partial or total deletion of one X chromosome. Two hypotheses have been proposed to explain the findings in A. azarae. In the first it is assumed that XX, Xx and XO females are fertile and able to produce X, x and 0 ova to give XX, Xx and XO females after fertilization by a X-bearing sperm. The second hypothesis proposes and extreme mechanism of sex dosage compensation ranging from X-chromosome inactivation, to partial or total X chromosome elimination. These hypotheses are tested by analysing the chromosome complement in the offspring derived from mating pairs of A. azarae of known chromosome constitution.The offspring obtained from XX x XY mating pairs showed: a) a sex ratio of 0.67 females per male, b) an average litter size of 3.8 pups, c) the lack of Xx or XO females. The offspring derived from Xx females had: a) a sex ratio of 1.73 females per male, b) a ratio of 0.64 XX females per each Xx female, c) an average litter size of 4.8 pups. The results obtained do not fit the predictions of the fertilization or the sex dosage compensation hypothesis. However, they can be explained by combining the fertilization hypothesis with a rate of lethality of XX zygotes. The possible cause of the XX zygote lethality and the eventual relationship between sex chromosomal polymorphism and density cycles in natural populations of A. azarae are discussed. Moreover, it is presented evidence stressing the instability of deleted X chromosomes.

Differential sex chromosome replication and dosage compensation in polytene trichogen cells of Lucilia cuprina (Diptera: Calliphoridae)

Abstract: Non banded sex chromosome elements have been identified in polytene trichogen cells of Lucilia cuprina using Y-autosome translocations, C-banding and Quinacrine fluorescence. The X chromosome is an irregular granular structure while the much smaller Y chromosome has both a dense darkly stained and a loosely organised segment. The X and Y chromosomes are underreplicated in polytene cells but comparison of C- and Q-banding characteristics of sex chromosomes in diploid and polytene tissues indicates that selective replication of non C-banding material occurs in both the sex chromosomes. Brightly fluorescing material in the Y chromosome is replicated to such an extent that it consists of half the polytene element, while the C-banding material, which makes up most of the diploid X chromosome, is virtually unreplicated. Differential replication also occurs in autosomes. In XXY males, and in males carrying a duplication of the X euchromatic region, a short uniquely banded polytene chromosome is formed. It is suggested that in males carrying two doses of X euchromatin a dosage compensation mechanism operates in which genes in one copy are silenced by forming a banded polytene chromosome.

Segmental heterogeneity in replication and transcription of the X 2 chromosome of Drosophila miranda and conservativeness in the evolution of dosage compensation

Abstract: A detailed analysis of the replication and transcription patterns of the X chromosomes of Drosophila miranda has been made using 3H-thymidine and 3H-uridine autoradiography. The purpose of this investigation has been to examine the relative duration of replication and hyperactivity of the different regions of the X2 element of this species. Results reveal that there is a considerable amount of heterogeneity among different segments of the X2 but not among the segments of X1 chromosome. Secondly, there is a clear site wise relationship between early replication and hyperactivity in X1 as well as X2. Thirdly, the X2 element appears to replicate relatively earlier than the X1 element in the male. — Our data do not support a spreading effect or polarization in the distribution of hyperactive segments. Furthermore, the X2 element appears relatively thinner than X1 in almost all nuclei from male larval glands. The significance of these results has been discussed in the light of the conservativeness of dosage compensation mechanism in a particular evolutionary line.

The relationship between gene dosage, gene expression, and sex in Drosophila

Abstract: In Drosophila, the ratio of the number of X chromosomes to sets of other chromosomes initiates a series of events which result in sexual differentiation. In addition, this ratio establishes dosage compensation, a mechanism which equalizes the products of X-linked genes in males and females. The present review discusses possible genetic entities responsible for the interpretation of chromosomal sex and subsequent sex-mediated regulation during development.

Dosage compensation of serine-4 transfer RNA in Drosophila melanogaster.

Abstract: A dosage series of the X chromosome site for serine-4 transfer RNA consisting of one of three copies in females and one to two in males was constructed to test whether transfer RNA expression is governed by dosage compensation. A dosage effect on the level of the serine-4 isoacceptor was observed in both females and males when the structural locus was varied. However, in males, each dose had a relatively greater expression so the normal one dose was slightly greater than the total female value and the duplicated male had the highest relative expression of all the types examined. Serine-4 levels in males and females from an isogenic Oregon-R stock were similar. Thus the transfer RNA levels conform to the expectations of dosage compensation.

Dosage compensation and sex determination in Drosophila : mechanism of measurement of the X/A ratio

Abstract: We propose a molecular mechanism for the intra-cellular measurement of the ratio of the number of X chromosomes to the number of sets of autosomes, a process central to both sex determination and dosage compensation inDrosophila melanogaster. In addition to the two loci,da andSxl, which have been shown by Cline(Genetics, 90, 683, 1978)and others to be involved in these processes, we postulate two other loci, one autosomal (Ω) and the other, X-linked (π). The product of the autosomal locusda stimulates Ω and initiates synthesis of a limited quantity of repressor.Sxl and π ,both of which are X-linked, compete for this repressor as well as for RNA polymerase. It is assumed thatSxl has lower affinity than π for repressor as well as polymerase and that the binding of polymerase to one of these sites modulates the binding affinity of the other site for the enzyme. It can be shown that as a result of these postulated interactions transcription from theSxl site is proportional to the X/A ratio such that the levels ofSxl + product are low in males, high in females and intermediate in the intersexes. If, as proposed by Cline, theSxl - product is an inhibitor of X chromosome activity, this would result in dosage compensation. The model leads to the conclusion that high levels ofSxl + product promote a female phenotype and low levels, a male phenotype. One interesting consequence of the assumptions on which the model is based is that the level ofSxl + product in the cell, when examined as a function of increasing repressor concentration, first goes up and then decreases, yielding a bell-shaped curve. This feature of the model provides an explanation for some of the remarkable interactions among mutants at theSxl, da andmle loci and leads to several predictions. The proposed mechanism may also have relevance to certain other problems, such as size regulation during development, which seem to involve measurement of ratios at the cellular level.

Evidence for X-linkage and non-inactivation of steroid sulphatase locus in wood lemming

Abstract: One of the two X chromosomes is inactivated in somatic cells of adult female mammals to compensate for unequal amounts of X-chromosomal genes in the two sexes1. Although the general validity of this concept is not in doubt, there is evidence that a segment of the distal short arm of the human X chromosome carrying the gene, or genes for the Xg blood group system, the steroid sulphatase (STS) locus2,3, and a gene controlling a serologically defined male-specific antigen4,5, is never inactivated. It is not known whether this non-inactivated segment is a special feature of the human X chromosome or whether it is a general feature of the ancestral, highly conserved, mammalian X chromosome6. In man the number of functional STS gene copies can be deduced from intracellular STS activity7. With this in mind we have investigated the number of active gene copies on the X chromosome of the wood lemming (Myopus schistfcolor, Lilljeborg), by assaying STS in cultured cells of this species. We report here that STS activity is directly correlated to the number of X chromosomes and unrelated to the phenotypic sex. This suggests that in the wood lemming the STS gene is also X-linked and not subject to inactivation.

Insect sex chromosomes. VI. A presumptive hyperactivation of the male X chromosome in Acheta domesticus (L.).

Abstract: The functional status of the X chromosome in Acheta domesticus has been analysed at the whole chromosome level on the basis of (1) 3H-thymidine autoradiography, (2) 5-BrdU/AO fluorescence microscopy (3) in vivo 5-BrdU incorporation and (4) 3H-UdR induced aberrations. The rationale of these techniques in relation to the functional aspect of the X chromosome is that the inactive X chromosome would (1) show asynchrony in DNA synthesis, (2) show differential fluorescence, (3) respond differentially to in vivo 5-BrdU treatment and (4) the active X chromosome would show aberrations when treated with 3H-Uridine. From the results, it appears that the X chromosomes in both male (XO) and female (XX) somatic cells of Acheta are euchromatic (active). Further, the single X in the male is transcriptionally as active as the two X chromosomes in the female. In other words, the single X in the male is hyperactive when compared with the single X in the female. From this it is inferred that the male X chromosome is differentially regulated in order to bring about an equalization of it's gene product(s) to that produced by both Xs in the female. Drosophila melanogaster has a comparable system of dosage compensation. Thus, Acheta is yet another insect showing evidence for an X chromosome regulatory mechanism of dosage compensation. Additionally, it is surmised that sex determination in Acheta is based on an autosomes/X chromosome balance mechanism.

The LSP1-α gene is not dosage compensated in the Drosophila melanogaster species subgroup

Abstract: The X-linked α subunit of larval serum protein 1 (LSP1-α) is shown to lack dosage compensation in six members of the melanogaster species subgroup, viz., Drosophila melanogaster, D. simulans, D. mauritiana, D. erecta, D. yakuba, and D. teissieri, by quantitative filter hybridization and by electrophoretic and autoradiographic analyses of fat body proteins. These results support the hypothesis that there is little selection pressure on the LSP1-α gene to acquire dosage compensation.

Insect sex chromosomes

Abstract: The functional status of the X chromosome in Acheta domesticus has been analysed at the whole chromosome level on the basis of (1) 3H-thymidine autoradiography, (2) 5-BrdU/AO fluorescence microscopy, (3) in vivo 5-BrdU incorporation and (4) 3H-UdR induced aberrations. The rationale of these techniques in relation to the functional aspect of the X chromosome is that the inactive X chromosome would (1) show asynchrony in DNA synthesis, (2) show differential fluorescence, (3) respond differentially to in vivo 5-BrdU treatment and (4) the active X chromosome would show aberrations when treated with 3H-Uridine. From the results, it appears that the X chromosomes in both male (XO) and female (XX) somatic cells of Acheta are euchromatic (active). Further, the single X in the male is transcriptionally as active as the two X chromosomes in the female. In other words, the single X in the male is hyperactive when compared with the single X in the female. From this it is inferred that the male X chromosome is differentially regulated in order to bring about an equalization of it's gene product(S) to that produced by both Xs in the female. Drosophila melanogaster has a comparable system of dosage compensation. Thus, Acheta is yet another insect showing evidence for an X chromosome regulatory mechanism of dosage compensation. Additionally, it is surmised that sex determination in Acheta is based on an autosomes/X chromosome balance mechanism.

VI. A Presumptive Hyperactivation of the Male X Chromosome in Acheta domesticus (L.)

Abstract: The functional status of the X chromosome in Acheta domesti- cus has been analysed at the whole chromosome level on the basis of (1) 3H-thymidine autoradiography, (2) 5-BrdU/AO fluorescence micros- copy, (3) in vivo 5-BrdU incorporation and (4) 3H-UdR induced aberra- tions. The rationale of these techniques in relation to the functional aspect of the X chromosome is that the inactive X chromosome would (1) show asynchrony in DNA synthesis, (2) show differential fluores- cence, (3) respond differentially to in vivo 5-BrdU treatment and (4) the active X chromosome would show aberrations when treated with 3H-Uridine. From the results, it appears that the X chromosomes in both male (XO) and female (XX) somatic cells of Acheta are euchromatic (active). Further, the single X in the male is transcriptionally as active as the two X chromosomes in the female. In other words, the single X in the male is hyperactive when compared with the single X in the female. From this it is inferred that the male X chromosome is differen- tially regulated in order to bring about an equalization of it's gene prod- uct(s) to that produced by both Xs in the female. Drosophila melano- gaster has a comparable system of dosage compensation. Thus, Acheta is yet another insect showing evidence for an X chromosome regulatory mechanism of dosage compensation. Additionally, it is surmised that sex determination in Acheta is based on an autosomes/X chromosome balance mechanism.