Search

A phenotypically normal mother carries a balanced X-21 translocation. Autoradiography of the mother's cells reveals that in all cells the normal X is late replicating. Her only pregnancy produced like-sex twins, one of whom is phenotypically and karyotypically normal. The co-twin is mentally retarded and has multiple anomalies. Her karyotype is 46,XX,der(21),t(X;21)(q11;p11?)mat. In the majority of informative cells from the daughter, one normal X and the entire X t replicate late. This maintains X dosage compensation, but results in effective monosomy 21. The phenotype of the infant is similar to others with 21q−.

It is shown that the apparent incompleteness of dosage compensation when RNA synthesis is measured autoradiographically is not due to the existence of contiguous dosage compensated and non-dosage compensated genes. Rather this seems to be the result of peculiarities in the coordination of RNA synthesis between the X chromosomes and autosomes. The slope of the line defined by \([\bar X]_i \) and \([\overline {2R} ]_i \) (number of grains over the X and autosomal segments averaged over the different nuclei assayed in each gland) is indistinguishable in males and females (apparent complete dosage compensation). An average of the slopes obtained for different individual glands (from [X] and [2R], the grain counts over each nucleus belonging to a particular gland), on the other hand, has a value in males which is approximately half of the value attained by females (a value of one half, in males, indicates dosage effect since males have one X and females have two).

SUMMARYThe authors have examined the « banding pattern », revealed by the Seabright method (1972), of chromosomes of an aneuploid-diploid line (C-125) and of certain lines of various degrees of ploidy derived from it. It was found that the line C-125 has preserved a large proportion of normal chromosomes, similar to those of the species, some in a diploid and others in a haploid condition.Analysis of the degree of homology of the chromosomes confirmed that, in the derived polyploid lines, part of the genome is in a triploid condition (Oliveri et al. 1972) even if in some cases only parts of the chromosome are in a triploid condition as a result of deletions. This last type of chromosome rearrangement is the one that has had the greatest importance in the evolution of the karyogram of the induced polyploid lines. The results are discussed in relation to problems of « dosage compensation ».

The X-chromosome of mammals is remarkable for its variable genetic activity. In somatic cells only a single X-chromosome is active, no matter how many are present, thus providing a dosage compensation mechanism by which males and females effectively have the same gene dosage of X-linked genes. In germ cells, however, it appears that all X-chromosomes present are active. Female germ cells require the presence of two X-chromosomes for normal survival, whereas male germ cells die if they have more than one X-chromosome. This system is found in all eutherian mammals and in marsupials, but is not known in any other animal group. In marsupials the X-chromosome derived from the father seems to be preferentially inactivated, whereas in eutherian mammals that from either parent may be so in different cells of the same animal. The differentiation of a particular X-chromosome as active or inactive is initiated in early embryogeny, and thereafter maintained through all further cell divisions in that individual. The mechanisms by which this is achieved are of great interest in relation to genetic control mechanisms in general. Various recent hypotheses concerning these mechanisms are discussed.

The interphase nuclei of only a few tissues of males of Tachycines asynamorus exhibit one particularly condensed and large chromocenter, those of females two, on the contrary. This distribution of the sex chromatin indicates 1) failure of a dosage compensation such as in mammalian X's, and 2) the occurrence of a tissue-specific, functional heterochromatization of the one male X and of both female X's in several tissues.

A detailed analysis of the 3H-thymidine labelling pattern for a large fraction of the X (12A–20D) and a short section of the 4th (90C–94C) chromosome of Drosophila hydei with special emphasis on the 18 X-chromosomal puffs and 14 autosomal puffs is presented. Attempts to arrange the different labelling patterns into different ordered sequences lead to only one optimal sequence that fits with a continuous-to-discontinuous sequence of labelling, both at the level of whole chromosome sections as well as at the level of the 18 X-chromosomal and 14 autosomal puffs. This finding inplies that all genetically active sites start replication simultaneously and that each active locus may complete its replication according to the amount of DNA and/or the degree of puffing activity. The data suggest that the individual units behave autonomously. On the basis of the labelling frequency of the different non-puffed segments and puffing sites of the X and the 4th, it has been shown that (a) puff sites in most cases take a shorter time than non-puffed bands, and (b) the puff sites on the female X's require a longer period of replication as compared to the same puffs on the male X. These observations suggest that the asynchronous replication of the male X may be causally related to its hyperactivity. The data provide further evidence in support of piecemeal regulation of dosage compensation in Drosophila and reinstates the hyperactive male X model of dosage compensation.

Female heterogamety has been found in eight Australian species of Tephritidae belonging to Chrysotrypanea, Tephritis, and three new genera. Evidence suggests that female heterogamety evolved in response to selection through small potency changes in species of the Y/X or Y/XA types which lacked elaborate mechanisms for dosage compensation.

Thymidine-3H labeling patterns on the X (section 1 A to 12 E of Bridges' map) and 2 R (section 56 F to 60 F of Bridges' map) segments in the salivary gland chromosomes of Drosophila melanogaster have been analyzed in male and female separately. The observed patterns fit, with a few exceptions, in a continuous to discontinuous labeling sequence. In nuclei with similar labeling patterns on the 2R segment in both sexes, the number of labeled sites on the X in male is always less than in female X's. The labeling frequency of the different sites on the male X is considerably lower than those on the female X's, while the sites on the 2R segment have very similar frequency in the two sexes. The rate of thymidine-3H incorporation (as judged by visual grain counting) is relatively higher in male X than in female X's. It is concluded that the model sequence of replication in polytene chromosomes follows a continuous to discontinuous labeling sequence, and that the single X in male completes its replication earlier than either the autosomes in male or the X's in female. This asynchronous and faster rate of replication by the polytene X-chromosome in male substantiates the hypothesis of hyperactivity of the single X in male as the chromosomal basis of dosage compensation in Drosophila.

SUMMARYThe functional morphology and the replication pattern of the male X-chromosome in an autosome-X insertion stock (T(1;3) 05) of Drosophila melanogaster have been examined. In larval salivary glands carrying this insertion neither the enlargement and pale staining of the single male X, nor the characteristic early completion of replication cycle, as revealed by 3H-TdR autoradiography is in any way changed. The normal properties of the inserted autosomal segment are also unaltered. The results appear to support a ‘piecemeal’ type of dosage compensation mechanism in Drosophila operating through the male.

The phenomenon of somatic segregation is defined herein as the formation of two new diploid cell types within the body of an ordinary monozygotic individual. In these new cell types, either two paternallyderived chromosomes or two maternallyderived ones constitute a homologous pair. By this mechanism, two kinds of cells homozygous for either one or the other allele emerge within the body of an individual heterozygous for a given genetic locus.

IN the female mule (Equus caballus × E. asinus), the horse (maternal) and the donkey (paternal) X chromosomes are morphologically distinguishable1,2, and the X-linked enzyme, glucose-6-phosphate dehydrogenase (G-6-PD), is present as a combination of the two electrophoretically distinct parental forms3,4. Female mule cells therefore may serve as an experimental model for the simultaneous study of both cytological and biochemical aspects of dosage compensation for X-linked loci in mammals (Lyon hypothesis5). We have demonstrated a very close correlation between late replication of either one or the other of the parental X chromosomes, and relative activity of the complementary form of G-6-PD6. In this study we have obtained further and more rigorous proof that late replication of the X chromosome corresponds to genetic inactivation at the G-6-PD locus. We have also obtained data bearing on the problem of the postulated randomness of inactivation.

The level of activity of the enzyme glucose-6-phosphate dehydrogenase was determinel in flies having seven different chromosomic constitutions. All those having an integral number of chromosomes [XAA, XXAA, XAAA, XXAAA, and XXXAAA (X=X chromosome, A=set of autosomes)] were found to have similar units of enzyme activity/mg live weight, while diploid females with a duplication and triploid females with a deficiency showed dosage effect. The amount of enzyme activity per cell, on the other hand, is also independent of the number of X's present but appears roughly proportional to the number of sets of autosomes.—It is proposed that dosage-compensated sex-linked genes are controlled by a positively acting regulatory factor(s) of autosomal origin. With this hypothesis it is possible to explain dosage compensation as a consequence of general regulatory mechanisms without invoking a special device which applies only to the X chromosomes.

Contrary to opinions expressed by various authors, the phenotype of heterozygotes for mammalian sex-linked genes gives no support for the Lyon hypothesis (L.H.). Evidence, mainly from the mouse, shows that in such heterozygotes, both alleles act together as in autosomal genes.In the present paper, it is shown that neither the behaviour of double heterozygotes for sex-linked genes nor that of X-autosome translocations provides independent evidence in favour of the L.H.: in each case, the interpretation depends on that of the behaviour of single heterozygotes and hence fails to discriminate. Moreover, new facts from both types of situation are also contrary to the L.H. In particular, a unified interpretation which fits the behaviour of genes in all known types of X-autosome translocations in the mouse requires the assumption that partial inhibition of gene action happens in both X-chromosomes of mouse females, and presumably the females of other mammals. The new hypothesis is consistent with all relevant genetical facts and, like the L.H., it also accounts for dosage compensation.

A new sex-linked mutation in the flour beetle Tribolium castaneum is described and illustrated. Blob (bb), an antennal mutant, is located near the far right end of the known linkage map of the X chromosome. It is recessive, with incomplete penetrance and variable expressivity, and fails to exhibit dosage compensation. The expression of bb is discussed in relationship to models of antennal development in this species. Apparent rediscovery of the pegleg mutation has confirmed a previous report on the linkage relationships of pearl and pegleg in linkage group II.

1. Inactivation of one X chromosome in somatic cells of female mammals is a form of dosage compensation of sex-linked genes, but the mechanism is entirely different from that operating inDrosophila. The latter is designated as dosage compensationsensu strictu.2. There is no dosage compensation of barred,sex-linked dilutionorslow-featheringin domestic fowls, ofalmondorfadedin pigeons, or ofcinnamonin canaries. Among Lepidoptera the same is true ofsex-linked melanisminLymantria monachaand of a locus controlling haemolymph colour inChoritoneuraspp. There is no positive evidence that dosage compensation occurs outside Drosophila and mammals.3. Sex-chromatin in female birds (heterogametic) has been reported by several authors; the genetical evidence is against the possibility that this represents (as in mammals) an inactivated X chromosome. Sex-chromatin in the heterogametic sex also occurs in some (not all) Lepidoptera and Heteroptera; in Heteroptera it usually represents a heteropyknotic Y chromosome.4. Some complications in Muller's theory of dosage compensationsensu strictuare discussed. Not all ‘compensatory modifiers’ are necessarily sex-linked.5. The problem of dosage compensation in species with impaternate males is discussed;fusedinHabrobraconis not compensated.

SUMMARY Red cell glucose-6-phosphate dehydrogenase (G-6-PD) activity was measured in fourteen XXX, eleven XX Y, three XO individuals, four individuals who were 17 but had testicular feminization, and in appropriate male and female controls. No evidence for any quantitative relationship between the number of X-chromosomes present and the level of red-cell G-6-PD activity was observed. Since G-6-PD is known to be determined by at least one gene locus in the X-chromosome, these results in agreement with others imply complete dosage compensation. In thirteen patients with thyrotoxicosis a significant elevation of the mean level of red cell G-6-PD was demonstrated, indicating that such increases could be detected under the general conditions of the investigation. The results are discussed in terms of various hypotheses accounting for dosage compensation.

The DNA content of individual Feulgen-stained chromosomes of micro-sporidian-infected salivary gland cells was measured with a scanning micro-spectrophotometer, and usually falls into classes that approximate the geometric series 2:4:8:16:32 times the DNA content of uninfected polytene cells. Chromosomes of widely different sizes can belong to the same DNA class, indicating that chromosomes respond to infection by puffing at many loci (generalized puffing) as well as by increases in polyteny. The extreme puffing of the whole X of the male is further evidence that dosage compensation in Diptera is brought about by increasing the activity of loci throughout the single X chromosome of the male.

Chromosome measurements were performed in four species of snakes related at the level of suborder (Boa constrictor amarali, Xenodon merremii, Philodryas patagoniensis, Bothrops jararaca). The data obtained point out that pairs 1–3 were common to the four snakes and probably inherited from the ancestor of the suborder Serpentes. Pairs 5–8-W were characteristic of each snake; hence, it is possible to assume that they followed evolving after the appearing of the suborder Serpentes. Z-chromosomes were metacentric in B. constrictor amarali, X. merremii and B. jararaca and slightly submetacentric in P. patagoniensis. Area of these chromosomes varied from 8.6–10.6% of the haploid set in the four species studied.-The study of chromosome replication at the end of the S period points out that “shared chromosomes” have similar patterns of labeling. Therefore, it is proposed that the distribution of late replicating regions and heterochromatin in the genome is phylogenetically transmitted and probably genetically determined.—The analysis of the ending-sequence of chromosome replication shows that sex chromosomes finish earlier than macroautosomes. It is concluded that snakes probably have no mechanism of sex chromosome heterochromatinization in either sex. The absence of late replicating Z-chromosome in the males, favours the hypothesis that no mechanism of sex dosage compensation is acting in the suborder Serpentes.

SummaryThe expression of five eye-colour mutants of the honeybee was found to differ between workers and drones, but in an irregular fashion suggesting that dosage compensation in honeybees arises from the different developmental phases in the two sexes, and not from mechanisms that specifically adjust for the initial difference in ploidy. Queens of two of the mutants were also examined and were found to differ from both workers and drones, so nutritional differences may be reflected by mutant gene expression.

The amount of DNA complementary to ribosomal RNA in normal individuals and nucleolar mutants of Xenopus laevis has been determined using the low temperature-formamide hybridization technique. By crossing a heterozygous mutant having one large nucleolus and one partial nucleolus (+/ p l nu ) with an animal having only one nucleolus per cell (+/ o nu ), progeny carrying either the normal nucleolar organizer (+/ o nu ) or the mutant organizer ( p l /o nu ) were obtained. Mutants carrying only the p l nu organizer ( partial-lethal or p l nu ), which die at an early stage of development, have about 50% of the number of ribosomal RNA genes found in +/ o nu animals and 25% of the number found in normal diploids (+/+ nu ). Thus in +/ p l nu heterozygotes the difference in nucleolar size is related to an unequal distribution of rRNA genes between the + nu and p l nu nucleolar organizers. The deletion that produced the p l nu organizer included equal numbers of 28 s and 18 s RNA genes, agreeing with the view that these genes alternate in the nucleolar organizer. Thermal stability profiles of hybrids between rRNA of wild-type animals and DNA from wild-type or mutant animals were similar. This suggests that there is little, if any, base sequence divergence among the highly reiterated rRNA genes. In the accompanying paper it was shown that the lethal, p l /o nu mutants synthesize rRNA at less than the normal rate. Since +/ o nu embryos develop normally and synthesize rRNA at normal rates, it is likely that the number of rRNA genes necessary for normal development and for normal rRNA synthesis is between 25 and 50% of the diploid number. These results show that dosage compensation does not necessarily occur when the number of rRNA genes is reduced to below the haploid number.

Discoveries in cytology that have led to the clarification of genetic phenomena are reviewed. Mammalian sex determination, male antigen in mice, meiotic cytology, variegation in Drosophila and mice, dosage compensation, and variegation and dosage compensation in mammals are discussed.

The inactive-X theory of dosage compensation postulates that in all somatic cells of adult female mammals one or other of the two X chromosomes is genetically inactive. This means that in a female heterozygous for two non-allelic genes acting through the same cells, and carried one on each X chromosome, one or other gene should act in all cells. Conversely, if the two genes are carried on the same X, then both genes should act in some cells and neither gene in the remainder. This point has been tested by breeding experiments with mice, using pairs of genes affecting coat colour and coat texture. In female mice carrying the colour mutant dappled,Modp, on one X and a translocation including the wild-type alleles of pink-eye,p, and albino,c, on the other, eitherModpor the translocation acted in all cells. With the genes tabby,Taand striated,Str, affecting coat texture, inStr + / + Tafemales tabby acted only in the non-Strpatches, while inStrTa/ + + it acted only in theStrones. Thus these experiments confirm that only one of the two X chromosomes is active in the somatic cells of female mammals.

SUMMARYRhynchosciara angelae has 8 chromosomes in somatic cells in females (2A+XX) and 7 in males (2A+X0). As females have two Xs and males only one, and the expression of the genes is the same in both sexes, there is a mechanism of dosage compensation for the X-linked genes. The single X polytene chromosome of males is paler than those of females, but has almost the same width. We studied the DNA and RNA synthesis in the sex chromosomes and in the autosomes of males and females in order to investigate dosage compensation at the chromosomal level.We injected tritiated thymidine or uridine into 44-day old larvae of R. angelae. We also placed salivary glands in a medium with tritiated thymidine or uridine. The intensity of DNA and RNA metabolism was evaluated by the number of silver grains per unit of area in the autoradiographs. The results suggest that there is an activation of the X-chromosome in males in relation to RNA synthesis, and at the same time an inactivation of the autosomes in the males.

The three theories of dosage compensation inDrosophilaare examined. Data are presented supporting a developmental interpretation. The reason why such a mechanism is applicable in insects but not in mammals is discussed.

There are certain genes on the sex chromosome of Drosophila for which the female contains twice as many copies as the male. Some of the genes in this group produce the same phenotype in each sex despite the dosage difference and are said, therefore, to manifest dosage compensation. The structural genes for glucose-6-phosphate and 6-phosphogluconate dehydrogenases are located on the sex chromosome. We measured these enzyme activities in normal flies of each sex and in flies bearing fewer or extra copies of these genes. Normal females (two-dose) had the same 6-phosphogluconate dehydrogenase activity as normal males (one-dose). One-dose females had reduced activity (0.61 of normal) and three-dose females or two-dose males had increased activity (about 1.3 of normal). Triploid females had the normal activity. Glucose-6-phosphate dehydrogenase activity responded similarly to gene dosage. Neither activity responded to changes in the dosage of the gene for the other. These results are compatible with an interpretation whereby each activity is compensated by the products of at least two regulatory genes. One of these regulatory genes is probably sex-linked; the others may be sex-linked or autosomal.

1. Autosexing breeds of fowl may be divided into those which carry the sex-linked gene for barring (B), and those which do not. In the former group, the autosexing properties are due to the imperfect dominance of B. 2. A table (Table 2) is presented showing the possible dominance relations between a sex-linked gene which is a hypomorph, hypermorph, antimorph, amorph or neomorph, and its wild-type allele, both without dosage compensation, and in conditions of partial and full dosage compensation. 3. A study of the ‘ticks’occurring on birds having various constitutions for the two sex-linked loci B and S silver) shows that the ticks are due to somatic elimination of part of an X-chromosome. It shows further that B is a neomorph (b having no action on pigmentation) without dosage compensation, or possibly a hypomorph (b having a very weak action in the same direction as B) with, at most, a slight degree of dosage compensation. This in itself is sufficient to explain the autosexing properties of barred breeds, without resorting to the improbable assumption that females have a Y-chromosome which carries b. 4. Anomalies are pointed out in the dominance relations at several sex-linked loci (w, A, B, Hw) ofDrosophila melanogaster, which are difficult to explain on Muller’s theory of dosage compensation. 5. There is no reason to attribute any autosexing effect to either allele at the silver locus of the fowl. There is some evidence to suggest that the sex hormones, rather than a specific sex-linked gene with a dosage effect similar to that of B, are responsible for autosexing in non-barred breeds. On whether the testicular or the ovarian hormone is responsible, the available evidence is conflicting.

SEX linked genes are usually expressed equally in both sexes of Drosophila, although they are present as a single dose in males and a double dose in females. This is known as dosage compensation1, a term also used when abnormal increases or decreases of gene doses are compensated. If phenotypic expression deviates from dosage compensation towards an effect proportional to the gene dose2 the term “dosage effect” is used.

IN man, dosage compensation is achieved by random genetic inactivation of one X chromosome in each female cell early in embryonic life1; all descendants of this X chromosome then remain genetically inactive. The inactive X chromosome is late replicating and manifests itself as a sex chromatin body in the interphase somatic nuclei of females2,3. Because sex chromatin appears in human embryos approximately 12 days after conception4, it is presumed—although not certain—that X inactivation (Lyonization)5 occurs at this time. All human X-linked loci which have been tested hitherto have shown evidence of dosage compensation1. It is significant, however, that with one exception all these studies have been on older children or adults. A problem with the Lyon hypothesis is the existence of clinical abnormalities, particularly those of a non-sex-related nature, in patients with an abnormal number of X chromosomes. It suggests1,6 either that great damage can be done to human development by an abnormal number of X chromosomes before X-inactivation or that at least some X-linked loci must escape dosage compensation to a significant extent. This study supports the latter concept.

The gene competition model, originally formulated from studies on the regulation of alcohol dehydrogenase activity in maize, is also applicable to the phenomenon of dosage compensation in Drosophila. The model accounts for the absence of dosage compensation in sex determination.

We have investigated the occurrence of dosage compensation in D. willistoni and D. pseudoobscura, two species whose X chromosome is metacentric with one arm homologous to the X and the other homologous to the left arm of chromosome 3 of D. melanogaster. Crude extracts were assayed for isocitrate dehydrogenase (XR), glucose-6-phosphate dehydrogenase (XL?), 6-phosphogluconate dehydrogenase (XL?), and α-glycerophosphate dehydrogenase (chromosome 2) in D. willistoni, and for esterase-5 (XR), glucose-6-phosphate dehydrogenase (XL?), 6-phosphogluconate dehydrogenase (XL?) and amylase (chromosome 3) in D. pseudoobscura. Our results indicate that a mechanism for dosage compensation is operative in both arms of the X chromosome of these two species.

The sex-linked Pgd+ and Zw+ genes of Drosophila melanogaster and their associated enzyme activities 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase were employed in an analysis of the relationship between dosage compensation and the location of genes in the genome. In the genotypes examined, the enzyme activity specified by each copy of the gene is twice in males what it is in females. This is true of normal, structurally rearranged, and duplication genotypes. Dosage compensation, therefore, is a regulatory function associated with single structural genes or small chromosomal segments and does not depend on the gene's physical location on the X chromosome.

The intensity of transcription in the polytene X-chromosome of the salivary glands of Drosophila melanogaster has been determined as a function of the ratio of X-chromosomes to autosomes (X:A). Autoradiographic measurements revealed that the single X-chromosome in males (1X2A) incorporates twice as much label as each of the two X-chromosomes in females (2X2A) which confirms the earlier report of Mukherjee and Beermann (1965). The addition of the third autosome set in super-males (1X3A) does not result in an increase of RNA synthesis in the X-chromosomes as compared to normal males (1X2A). In superfemales (3X2A) carrying an extra X-chromosome the transcription in each of the X-chromosomes proceeds with the same rate as in diploid (2X2A) or triploid (3X3A) females. In intersexes (2X3A) the rate of transcription in each of X-chromosomes is intermediate between male and female levels. — The comparison of transcription rates in X-chromosomes with the levels of two enzymes coded for by sex-linked genes in males, females, super-females and intersexes (Faizullin and Gvozdev, 1972, 1973) revealed that the dosage compensation of the enzyme synthesis is effected at the level of transcription.

INACTIVATION of chromosomal elements is a process which takes place in various organisms, cell types, and cell cycle stages. The reasons for chromosome inactivation, which is superimposed on the more specific level of gene control, are different for the various systems. Dosage compensation in female mammals us. mitotic chromosome shut-off are the extreme cases. Since in many systems every chromosome may be in an active or inactive form, it is reasonable to assume, for the time being, that the molecular mechanism in different organisms is similar, thus justifying generalization. The role and behaviour of sex chromosomes during gametogenesis provide a striking example of differentiation of chromosomal elements and by inference reflect chromosome function. Precocious inactiviation of the X chromosome during seprmatogenesis together with activation of fertility factors on the Y in some organisms are of particular interest. In view of cytological and genetic observations we suggest a working hypothesis according to which the X choromsome is inactivated during a critical stage of spermatogenesis in all male heterogametic organisms. As the inactivation is an essential control and not a compensatory step, any interference with this process will change the developmental course of the spermatocyte leading to dominant male sterility (LIFSCHYTZ and LINDSEY 1972). In the course of this paper, the observations that support or lead to this view will be presented. Several experimental approaches we have undertaken to study further the genetics of the phenomenon, as well as its relation to Y chromsome activation, will be discussed.

Ohno and Hauschka1 showed that in female mice one chromosome of mammary carcinoma cells and of normal diploid cells of the ovary, mammary gland and liver was heteropyknotic. They interpreted this chromosome as an X-chromosome and suggested that the so-called sex chromatin was composed of one heteropyknotic X-chromosome. They left open the question whether the heteropyknosis was shown by the paternal X-chromosome only, or the chromosome from either parent indifferently.

A study of gene activity in diploid and triploid Drosophila melanogaster females has been performed. Levels of enzyme activity of X-linked glucose 6-phosphate and 6-phosphogluconate dehydrogenases and autosome-linked α-glycerophosphate and NADP-dependent isocitrate dehydrogenases were measured and correlated with DNA content, in crude extracts of whole flies or thoraces. The results show that the contribution of each dose of a given gene to the level of enzyme activity is equal in diploid and triploid cells. These findings are discussed in the context of the phenomenon of dosage compensation.

As shown in the previous chapter, the X-linked genes of Drosophila are included in the euchromatic region which never becomes heterochromatic. The male is endowed with one dose, while the female receives two doses of the euchromatic region of the X. During the course of evolution of this insect, the dosage compensation mechanism must have developed one by one for each individual X-linked gene.

Although they possess the nearly identical DNA value, placental mammals of today display an enormous array of karyotypes, with diploid chromosome numbers ranging from a high of 80 to a low of 17. This indicates that during extensive speciation from a common ancestor, autosomal linkage groups have undergone countless rearrangements. Yet, the original X-chromosome of a common ancestor has apparently been preserved in its entirety by a great majority of placental mammals of today, and in its multiplicated forms by a small number of exceptional species. This conservation of the original X as one unit clearly reveals that the type of X-autosome translocations which split the original X into two separate halves has always been severely deteriorative to speciation, and that these translocations were eliminated as they arose.

The invariably hemizygous expression of the X-linked gene in the mammalian female should result in the visibly mosaic appearance of heterozygous females if the female carries a mutant gene which affects individual melanocytes or epidermal cells.