Showing papers on "Dosage compensation published in 1989"
TL;DR: It is shown that the Sxl transcription unit spans a DNA segment of greater than 20 kb and encodes at least 10 distinct, but overlapping, RNA species and exhibit sex, stage, and tissue specificity.
Abstract: For proper sexual development of females, the Sex-lethal (Sxl) gene must be activated early in development and remain on during the rest of the life cycle. Conversely, in males, Sxl must remain functionally off through development. Here, we show that the Sxl transcription unit spans a DNA segment of greater than 20 kb and encodes at least 10 distinct, but overlapping, RNA species. These RNAs range in size from 4.4 to 1.7 kb and exhibit sex, stage, and tissue specificity. Six RNAs, three female specific and three male specific, are first detected by midembryogenesis and persist through the adult stage: Their expression reflects the on/off regulation of Sxl's activity at the level of sex-specific alternate splicing. Four Sxl RNAs are found in adult females. Two of these RNAs are dependent on the presence of a functional germ line and may be relevant to Sxl's role in adult germ-line development. All four are present in unfertilized eggs. Finally, three Sxl RNAs are found only transiently during very early embryogenesis; we suggest that the expression of these RNAs may reflect an early regulation of Sxl at the level of transcription and that these transcripts are involved in the initial selection of the Sxl activity state in response to the primary sex-determination signal, the X/A ratio.
128 citations
TL;DR: Molecular studies of the X and Y chromosomes in humans and mice have provided clues to mammalian sex chromosome function and evolution and the pseudoautosomal boundary has been cloned and sequenced.
128 citations
TL;DR: It is found that the scute (T4) gene, which is involved in neurogenesis, also plays a role in the activation of Sxl, and the following results suggest that scute may be a numerator element of the X:A signal.
Abstract: The ratio of X chromosomes to sets of autosomes (X:A) is the primary genetic signal that determines sex and dosage compensation in Drosophila. The gene Sex-lethal (Sxl) receives this signal and is responsible for the execution of the alternative developmental programmes of males and females. We have found that the scute (T4) gene, which is involved in neurogenesis, also plays a role in the activation of Sxl. The following results suggest that scute (T4) may be a numerator element of the X:A signal: scute (T4) mutations show female-specific lethality. There are female-specific lethal synergistic interactions between sis-a, a previously described numerator element, and mutants for T4. The female lethality is suppressed by SxlM1, a constitutive allele which expresses an active Sxl product independently of the X:A ratio. The Hw685 mutation, which overexpresses T4, is lethal to males with a duplication of sis-a. This lethality is suppressed by either Sxlf1, or the T4 point mutation sc10-1. There are female-specific lethal interactions between sc10-1 and daughter-less (da), a gene needed maternally for Sxl to become active. The sc10-1 mutation masculinizes triploid intersexes.
94 citations
TL;DR: A genetic characterization of several essential components of the dosage compensation process in Caenorhabditis elegans suggests that dosage compensation is functioning in XX animals by mid-embryogenesis, when many zygotically transcribed genes are active.
Abstract: We report a genetic characterization of several essential components of the dosage compensation process in Caenorhabditis elegans. Mutations in the genes dpy-26, dpy-27, dpy-28, and the newly identified gene dpy-29 disrupt dosage compensation, resulting in elevated X-linked gene expression in XX animals and an incompletely penetrant maternal-effect XX-specific lethality. These dpy mutations appear to cause XX animals to express each set of X-linked genes at a level appropriate for XO animals. XO dpy animals are essentially wild type. Both the viability and the level of X-linked gene expression in XX animals carrying mutations in two or more dpy genes are the same as in animals carrying only a single mutation, consistent with the view that these genes act together in a single process (dosage compensation). To define a potential time of action for the gene dpd-28 we performed reciprocal temperature-shift experiments with a heat sensitive allele. The temperature-sensitive period for lethality begins 5 hr after fertilization at the 300-cell stage and extends to about 9 hr, a point well beyond the end of cell proliferation. This temperature-sensitive period suggests that dosage compensation is functioning in XX animals by mid-embryogenesis, when many zygotically transcribed genes are active. While mutations in the dpy genes have no effect on the sexual phenotype of otherwise wild-type XX or XO animals, they do have a slight feminizing effect on animals whose sex-determination process is already genetically perturbed. The opposite directions of the feminizing effects on sex determination and the masculinizing effects on dosage compensation caused by the dpy mutations are inconsistent with the wild-type dpy genes acting to coordinately control both processes. Instead, the feminizing effects are most likely an indirect consequence of disruptions in dosage compensation caused by the dpy mutations. Based on the cumulative evidence, the likely mechanism of dosage compensation in C. elegans involves reducing X-linked gene expression in XX animals to equal that in XO animals via the action of the dpy genes.
93 citations
TL;DR: The results show that sex determination in the germ line is more complex than in the soma, and that the state of activity of Sxl is regulated not only by the X:A ratio, but also by somatic inductive stimuli.
Abstract: We have analyzed the mechanism of sex determination in the germ line of Drosophila by manipulating three parameters: (1) the ratio of X-chromosomes to sets of autosomes (X:A); (2) the state of activity of the gene Sex-lethal (Sxl), and (3) the sex of the gonadal soma. To this end, animals with a ratio of 2X:2A and 2X:3A were sexually transformed into pseudomales by mutations at the sex-determining genes Sxl (Sex-lethal), tra (transformer), tra-2 (transformer-2), or dsx (double-sex). Animals with the karyotype 2X;3A were also transformed into pseudofemales by the constitutive mutation SxlM1. The sexual phenotype of the gonads and of the germ cells was assessed by phase-contrast microscopy. Confirming the conclusions of Steinmann-Zwicky et al. (Cell 57, 157, 1989), we found that all three parameters affect sex determination in germ cells. In contrast to the soma in which sex determination is completely cell-autonomous, sex determination in the germ line has a non-autonomous component inasmuch as the sex of the soma can influence the sexual pathway of the germ cells. Somatic induction has a clear effect on 2X;2A germ cells that carry a Sxl+ allele. These cells, which form eggs in an ovary, can enter spermatogenesis in testes. Mutations that cause partial loss of function or gain of function of Sxl thwart somatic induction and, independently of the sex of the soma, dictate spermatogenesis or oogenesis, respectively. Somatic induction has a much weaker effect on 2X;3A germ cells. This ratio is essentially a male signal for germ cells which consistently enter spermatogenesis in testes, even when they carry SxlM1. In a female soma, however, SxlM1 enables the 2X;3A germ cells to form almost normal eggs. Our results show that sex determination in the germ line is more complex than in the soma. They provide further evidence that the state of Sxl, the key gene for sex determination and dosage compensation in the soma, also determines the sex of the germ cells, and that, in the germ line, the state of activity of Sxl is regulated not only by the X:A ratio, but also by somatic inductive stimuli.
89 citations
TL;DR: A model in which sdc-2 is involved in the coordinate control of both sex determination and dosage compensation in XX animals and acts in the regulatory hierarchy at a step prior to the divergence of the two pathways is proposed.
Abstract: We have identified a new X-linked gene, sdc-2, that controls the hermaphrodite (XX) modes of both sex determination and X chromosome dosage compensation in Caenorhabditis elegans. Mutations in sdc-2 cause phenotypes that appear to result from a shift of both the sex determination and dosage compensation processes in XX animals to the XO modes of expression. Twenty-eight independent sdc-2 mutations have no apparent effect in XO animals, but cause two distinct phenotypes in XX animals: masculinization, reflecting a defect in sex determination, and lethality or dumpiness, reflecting a disruption in dosage compensation. The dosage compensation defect can be demonstrated directly by showing that sdc-2 mutations cause elevated levels of several X-linked transcripts in XX but not XO animals. While the masculinization is blocked by mutations in sex determining genes required for male development (her-1 and fem-3), the lethality, dumpiness and overexpression of X-linked genes are not, indicating that the effect of sdc-2 mutations on sex determination and dosage compensation are ultimately implemented by two independent pathways. We propose a model in which sdc-2 is involved in the coordinate control of both sex determination and dosage compensation in XX animals and acts in the regulatory hierarchy at a step prior to the divergence of the two pathways.
83 citations
TL;DR: The neo-Y chromosome of Drosophila miranda, an ancestral autosome that has become attached to the Y chromosome and is now partially heterochromatic, is analyzed and it is found that the added sequences are as devoid of mono- and dinucleotide repeats as otherheterochromatin.
Abstract: Long stretches of (dC-dA)n.(dT-dG)n, abbreviated CA/TG, have a distinctive distribution on Drosophila chromosomes (M.L. Pardue, K. Lowenhaupt, A. Rich, and A. Nordheim, EMBO J. 6:1781-1789, 1987). The distribution of CA/TG suggests a correlation with the overall transcriptional activity of chromosomal regions and with the ability to undergo meiotic recombination. These correlations are conserved among Drosophila species and may indicate one or more chromosomal functions. To test the generality of these findings, we analyzed the distribution of the rest of the six possible mono- and dinucleotide repeats (A/T, C/G, AT/AT, CA/TG, CT/AG, and CG/CG). All but CG/CG were present at significant levels in the genomes of the six Drosophila species studied; however, A/T levels were an order of magnitude lower than those of the other sequences. Data base analyses suggested that the same sequences are present in other eucaryotes. Like CA/TG, both CT/AG and C/G showed increased levels on dosage-compensating chromosomes; however, the individual sites clearly differed for each sequence. In contrast, A/T and AT/AT, although present in Drosophila DNA, could not be detected in situ in polytene chromosomes. We also used in situ hybridization to analyze the neo-Y chromosome of Drosophila miranda, an ancestral autosome that has become attached to the Y chromosome and is now partially heterochromatic. The neo-Y has acquired repeated DNA sequences; we found that the added sequences are as devoid of mono- and dinucleotide repeats as other heterochromatin. The distribution and function of these sequences are likely to result from both their repetitious nature and base contents.
70 citations
TL;DR: An alteration in the interphase structure of the human inactive X chromosome in hybrid cells which may explain its known instability with respect to genetic activity in such systems is indicated.
Abstract: A fluorescence in situ hybridization method using a biotinylated DNA probe specific for the centromeric region of the human X chromosome was used to differentiate the genetically active from the inactive X in interphase cells. With this technique, we were able to interpret both the relative position and the degree of condensation of the X chromosomes within the nucleus. We first established the specificity of fluorescence labelling of the hybridized probe by comparing its location and appearance (either dense or diffuse) when associated with a sex chromatin body (SCB) in early passage normal human female fibroblasts. In these cells, where the presence of inactive X chromatin was verified by identification of a 4',6-diamidino-2-phenyl indole (DAPI)-positive SCB in 85% of the cells examined, the X chromatin fluorescence was always associated with the SCB. The signal was dense in structure in 98% and peripheral in location in 80% of the nuclei. A second type of signal, diffuse in form, was observed in 85% of the nuclei and presumably represents the location of the active X chromosome. It was located peripherally or centrally with equal frequency and was not associated with any identifiable nuclear component. This diffuse signal was the major type associated with human male fibroblasts. In rodent x human hybrid cells containing a human inactive X, the fluorescent signal was associated with an SCB-like structure in only 13% of the nuclei; it was dense in 66% of the nuclei and equally peripheral or central in location. This indicates an alteration in the interphase structure of the human inactive X chromosome in hybrid cells which may explain its known instability with respect to genetic activity in such systems.
59 citations
TL;DR: The synergism found between ewG, vtw and ewg, sr as well as the dosage effect of the distal end of the X chromosome upon the expression of eWg and sr suggests the existence of functional relationships among the loci analyzed.
55 citations
TL;DR: This chapter describes X-chromosome inactivation as a system of gene dosage compensation to regulate gene expression in mammals and Drosophila and these systems show considerable differences.
Abstract: Publisher Summary X-inactivation center is thought to play a critical role, and the evidence for this comes from mouse X-autosome translocations. In such translocations, inactivation spreads from the X- chromosome into the attached autosomal material and can be detected by variegation in the expression of the coat-color genes located in the autosomal segment. This chapter describes X-chromosome inactivation as a system of gene dosage compensation to regulate gene expression. The two most extensively studied systems of gene dosage compensation are those in Drosophila melanogast er and in mammals and these systems show considerable differences. The most striking feature of the mammalian system is that two homologous chromosomes, the two X chromosomes of females, behave differently within the same cell, whereas in Drosophila homologs within a cell behave similarly and the compensation is obtained by differential chromosome behavior in the two sexes. A further difference is seen when the X chromosome is broken by translocations; in Drosophila , the different segments seem to behave autonomously, whereas in mammals, the behavior of separated segments is controlled by the X-inactivation center.
53 citations
TL;DR: It is reported that when cell cultures are established from these tissues, the silent G6PD locus is depressed, and observations suggest that without DNA methylation to maintain the silence of the locus, tissue or cell-specific factors act to repress the silent locus but are unable to maintain inactivity through cell division, or are lost as cells proliferate in culture.
TL;DR: It is proposed that the increased dosage of the X chromosome inversely affects both the X and autosomal gene expression but the simultaneous increased dosageof the structural genes on the X results in dosage compensation.
Abstract: The expression of selected X-linked and autosomal genes was examined in metafemales (3X:2A) compared to diploid sisters. Three enzyme activities (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, beta-hydroxyacid dehydrogenase) encoded by X-linked genes are not significantly different in the two classes of flies. In contrast, three autosomally encoded enzyme activities (alcohol dehydrogenase, alpha-glycerophosphate dehydrogenase, isocitrate dehydrogenase) are reduced in metafemales. Protein and DNA comparisons between metafemales and diploid sisters show a lowered level of total protein whereas the total DNA measurements are similar. Thus, the total cell number in metafemales is basically unchanged but gene expression is reduced. Phenotypic analysis of three autosomal loci, glass (gl), purple (pr) and pink-peach (pp), show that all three have lowered expression in metafemales while the X-linked loci, white-apricot (wa) and Bar (B), are dosage compensated. Quantitative dot blot analysis of messenger RNA levels of the second chromosomal locus, alcohol dehydrogenase (Adh), and the X chromosomal locus, rudimentary (r), show that Adh has reduced expression and r is partially compensated per total RNA in metafemales. It is proposed that the increased dosage of the X chromosome inversely affects both the X and autosomal gene expression but the simultaneous increased dosage of the structural genes on the X results in dosage compensation. The reduced levels of expression of autosomal genes could contribute to the great inviability of metafemales.
TL;DR: The molecular analyses of three of the regulatory genes controlling sexual differentiation in Drosophila have demonstrated that the control of RNA processing has a major role in regulating somatic sexual differentiation.
Abstract: The molecular analyses of three of the regulatory genes (transformer (tra), doublesex (dsx), and transformer-2 (tra-2)) controlling sexual differentiation in Drosophila have demonstrated that the control of RNA processing has a major role in regulating somatic sexual differentiation. The activities of both the tra and dsx genes are controlled at the level of RNA processing. In the case of tra the use of different splice acceptor sites results in a functional transcript being produced only in females, whereas at dsx the use of different splice acceptor sites in the two sexes results in the production of transcripts that encode different proteins in males and females. The tra-2 gene has been shown to be necessary for the processing of the dsx pre-mRNA in females and the conceptual translation of a tra-2 cDNA shows that it encodes a protein with similarity to a family of RNA-binding proteins which includes known splicesome components. We previously suggested that the pattern of sexual differentiation and dosage compensation characteristic of a male was a default regulatory state. The findings reviewed here provide a molecular basis for this default expression in males as well as an insight into how females differ from males in control of the expression of these genes. For both the tra and dsx genes the molecular basis of their male (default) state of expression appears to be the processing of their transcripts by the housekeeping RNA splicing machinery.(ABSTRACT TRUNCATED AT 250 WORDS)
01 Jan 1989
TL;DR: In this paper, a molecular analysis of three regulatory genes (transformer (tra), doublesex (dsx), and transformer-2 (tra-2)) controlling sexual differentiation in Drosophila has demonstrated that the regulatory genes have a major role in regulating somatic sexual differentiation.
Abstract: The molecular analyses of three of the regulatory genes (transformer (tra), doublesex (dsx), and transformer-2 (tra-2)) controlling sexual differentiation in Drosophila have demonstrated that the control of RNA processing has a major role in regulating somatic sexual differentiation. The activities of both the tra and dsx genes are controlled at the level of RNA processing. In the case of tra the use of different splice acceptor sites results in a functional transcript being produced only in females, whereas at dsx the use of different splice acceptor sites in the two sexes results in the production of transcripts that encode different proteins in males and females. The tra-2 gene has been shown to be necessary for the processing of the dsx premRNA in females and the conceptual translation of a tra-2 cDNA shows that it encodes a protein with similarity to a family of RNA-binding proteins which includes known splicesome components. We previously suggested that the pattern of sexual differentiation and dosage compensation characteristic of a male was a default regulatory state. The findings reviewed here provide a molecular basis for this default expression in males as well as an insight into how females differ from males in control of the expression of these genes. For both the tra and dsx genes the molecular basis of their male (default) state of expression appears to be the processing of their transcripts by the housekeeping RNA splicing machinery. In females the specification of the alternative pattern of splicing at both tra and dsx is by the sex determination regulatory genes that function upstream of them in this regulatory cascade. It seems likely that the activities of these sex determination regulatory genes in females do not provide all of the information that is necessary for proper splicing of the transcripts of the genes downstream of them. Rather we imagine that the products of the Sxl, tra, and tra-2 genes are acting to impose a specificity on the basic cellular splicing machinery.
TL;DR: This work introduces mutant alleles of the Sex-lethal locus into DrosophILA melanogaster-Drosophila simulans hybrids, implying that postzygotic isolation in this hybridization does not result from a disruption of dosage compensation caused by divergence of the X/A counting system.
Abstract: The X chromosome invariably has the largest effect on postzygotic isolation between animal species. One explanation of this pattern is that inviability and sterility result from a breakdown in the dosage compensation of X-linked genes in hybrids. In Drosophila, such breakdown could result from divergence of the genes used to assess the X/autosomal (X/A) ratio, and thus the sex, of an individual. I test this hypothesis by introducing mutant alleles of the Sex-lethal locus into Drosophila melanogaster-Drosophila simulans hybrids. These mutants "ignore" any perceived anomalous X/A ratio and thus can be used to ensure proper dosage compensation in hybrids. These mutants do not rescue hybrid viability or fertility, implying that postzygotic isolation in this hybridization does not result from a disruption of dosage compensation caused by divergence of the X/A counting system.
TL;DR: Using a heterologous rat cDNA probe, a transduced gene containing the X-linked gene Pgd+, which encodes the enzyme 6-phosphogluconate dehydrogenase (6PGD), is identified and it is concluded that the sequences responsible for dosage compensation of Pgd+ are included in this fragment.
Abstract: Using a heterologous rat cDNA probe, we have identified a 14.7 kbp Drosophila melanogaster genomic clone containing the X-linked gene Pgd+, which encodes the enzyme 6-phosphogluconate dehydrogenase (6PGD). We used in situ hybridization to larval polytene chromosomes, a somatic transient expression assay for enzyme activity, and the rescue of the lethal Pgd- phenotype by germline transformation to verify the identity of the gene. A 7.4 kbp fragment including the gene and approximately 1.2 kbp of upstream and 1.8 kbp of downstream sequences was relocated to autosomal ectopic sites by germline transformation; this transduced gene exhibits levels of enhanced activity in males comparable to those of the indigenous gene at its normal X chromosome locus. We conclude that the sequences responsible for dosage compensation of Pgd+ are included in this fragment.
TL;DR: Plethodontid salamanders in the genus Oedipina are characterized by a strongly heteromorphic sex-determining pair of X/Y chromosomes, and cytological evidence of dosage compensation, such as differential staining of the X chromosomes or Barr bodies, in mitotic or interphase cells from female animals is found.
Abstract: Plethodontid salamanders in the genus Oedipina are characterized by a strongly heteromorphic sex-determining pair of X/Y chromosomes. The telocentric X chromosome and the subtelocentric Y chromosome are clearly distinguished from the autosomes and their behavior during meiosis can be sequentially followed in squash preparations of spermatocytes. In Oedipina the sex chromosomes are not obscured by an opaque “sex vesicle” during early meiotic stages, making it possible to observe details of sex bivalent structure and behavior not directly visible in other vertebrate groups. The sex chromosomes can first be distinguished from autosomal bivalents at the conclusion of zygotene, with X and Y synapsed only along a short segment at their non-centromeric ends, forming a bivalent that contrasts sharply with the completely synapsed autosomes. During pachytene, the XY bivalent becomes progressively shortened and more compact, disappearing as a visible structure when pachytene progresses into the diffuse stage of male meiosis. Diplotene bivalents gradually emerge from the diffuse nuclei, presumably by the return of the loops of chromatin into their respective chromomeres. During early diplotene, the X/Y bivalent is clearly visible with a single chiasma within the synapsed segment. This chiasma is terminalized by first meiotic metaphase with the X and Y appearing either in end-to-end synaptic contact or as univalents separated at opposite poles relative to the equatorially distributed autosomal bivalents. In C-banded preparations, the Y is entirely heterochromatic while the X contains a large centromeric C-band and another block of heterochromatin located at the telomeric end, in the region of synapsis with the Y. We find no cytological evidence of dosage compensation, such as differential staining of the X chromosomes or Barr bodies, in mitotic or interphase cells from female animals.
TL;DR: It is concluded that the LSP1‐alpha gene is capable of dosage compensation and exhibits equivalent levels of transcripts in the two sexes when it is relocated to either an autosomal site or to an ectopic site on the X chromosome.
Abstract: The LSP1-alpha gene of Drosophila melanogaster is located on the X chromosome at 11B yet is not dosage compensated. In order to determine if this gene is inherently incapable of dosage compensation or if it does not compensate because the appropriate regulatory cis-acting sequences are absent from its chromosomal domain, we have undertaken to relocate it to ectopic sites on the X chromosome. To differentiate between the transcripts produced by the transduced gene and those produced by the indigenous gene, we inserted a 500-bp sequence of mouse DNA into the LSP1-alpha clone prior to using it for transformation. Our results show that the LSP1-alpha gene exhibits equivalent levels of transcripts in the two sexes when it is relocated to either an autosomal site or to an ectopic site on the X chromosome. We conclude that the LSP1-alpha gene is capable of dosage compensation.
01 May 1989
TL;DR: This paper considers the possible interactions between the msl genes that bring about dosage compensation in D. melanogaster and carried out the clonal analysis of one of those msl mutations: msl-3b.
Abstract: The male-specific lethal genes (msl) of D. melanogaster represent a set of genes whose functions are required for the specific X chromosome hypertranscription in males (dosage compensation). We have carried out the clonal analysis of one of those msl mutations: msl-3 b. Clones homozygous for msl-3 b are deleterious; this mutation presents cell autonomy and in the cases where msl clones appeared in sexually dimorphic regions (5th and 6th tergites) they do not show sexual transformation. Moreover, the lethal phase and the growth dynamics (measured by the protein content during larval growth) are the same for male larvae homozygous for one msl mutation (msl-1) or three msl mutations (msl-2 msl-1 mle), i.e. the msl mutations do not show additive effects. This paper considers the possible interactions between the msl genes that bring about dosage compensation.
TL;DR: Results indicate that upon transformation, the hprt gene on the inactive Chinese hamster X chromosome is rendered more susceptible to action by 5azaCR, consistent with a generalized DNA demethylation associated with the transformation event or with an increase in the instability of an underlying primary mechanism of X inactivation.
Abstract: We have investigated the genetic activation of the hprt (hypoxanthine-guanine phosphoribosyltransferase) gene located on the inactive X chromosome in primary and transformed female diploid Chinese hamster cells after treatment with the DNA methylation inhibitor 5-azacytidine (5azaCR). Mutants deficient in HPRT were first selected by growth in 6-thioguanine from two primary fibroblast cell lines and from transformed lines derived from them. These HPRT- mutants were then treated with 5azaCR and plated in HAT (hypoxanthine-methotrexate-thymidine) medium to select for cells that had reexpressed the hprt gene on the inactive X chromosome. Contrary to previous results with primary human cells, 5azaCR was effective in activating the hprt gene in primary Chinese hamster fibroblasts at a low but reproducible frequency of 2 x 10(-6) to 7 x 10(-6). In comparison, the frequency in independently derived transformed lines varied from 1 x 10(-5) to 5 x 10(-3), consistently higher than in the nontransformed cells. This increase remained significant when the difference in growth rates between the primary and transformed lines was taken into account. Treatment with 5azaCR was also found to induce transformation in the primary cell lines but at a low frequency of 4 x 10(-7) to 8 x 10(-7), inconsistent with a two-step model of transformation followed by gene activation to explain the derepression of hprt in primary cells. Thus, these results indicate that upon transformation, the hprt gene on the inactive Chinese hamster X chromosome is rendered more susceptible to action by 5azaCR, consistent with a generalized DNA demethylation associated with the transformation event or with an increase in the instability of an underlying primary mechanism of X inactivation.
TL;DR: The regulatory mechanism responsible for dosage compensation-the equalization of the products of X-linked genes in males and females-should be of particular interest to evolutionists because it is probably responsible for the evolution of heteromorphic sex chromosomes.
Abstract: Evolutionary theory, in the hands of population geneticists, has traditionally been developed by studying the causes and effects of fluctuations in the allelic frequencies of structural genes. The study of the evolution of basic regulatory mechanisms has lagged somewhat behind, with the stipulated exception of sex determination and its consequences. To date, the treatment of these phenomena has been, of necessity, in formal, theoretical terms. The imminent understanding of their molecular basis should allow a more profound understanding of their evolutionary history. The regulatory mechanism responsible for dosage compensation-the equalization of the products of X-linked genes in males and females-should be of particular interest to evolutionists for two main reasons. First, dosage compensation prevents differential selection between the sexes with respect to X-linked gene products that are equally useful to males and females. Second, the evolution of dosage compensation is probably responsible for, and c...