X chromosome

About: X chromosome is a research topic. Over the lifetime, 9862 publications have been published within this topic receiving 407354 citations. The topic is also known as: GO:0000805 & chrX.

Genetics of mammalian sex chromosomes.

Abstract: The great strides made during the past two years in the whole field of mammalian cytogenetics have, in particular, enlarged our knowledge of the role of the mammalian sex chromosomes. The following summary briefly lists the most recent discoveries in the mouse, where genetic findings have played a relatively greater role than in the other species of mammals. The male-determining property of the mammalian Y chromosome, established earlier in mouse and man, has been further confirmed by the finding of an XXY mouse, which was detected by genetic means and has been studied cytologically. This animal is a fully viable, phenotypically normal, though sterile, male. Since various doubts concerning detectability of the XXY type have been removed by the discovery of this animal, it can be concluded that the occurrence of XXY in the mouse is extremely rare. It has been shown that the X chromosome of the mouse, when it is involved in certain chromosomal rearrangements, has the power to produce variegated-type position effects, a phenomenon formerly not observed in any animal except Drosophila. The fact that the X chromosome is involved in all four of the known cases of V-type position effect in the mouse indicates that it is strongly heterochromatic, while there may be little heterochromatin on the autosomes. Recent findings have shown that the presence of two X chromosomes is necessary for the expression of the position effect in one of them. This fact, when related to various cytological findings in other species, permits the hypothesis that, in mammals, genic balance requires the action of one X in a manner which precludes realization of its heterochromatic potentialities, so that only any additional X's present assume the properties characteristic of heterochromatin. A variety of different findings sheds light on the mechanisms that may lead to the occurrence of individuals with abnormal numbers of sex chromosomes. The XXY mouse proves, by virtue of its sex-linked marker genes, that nondisjunction can occur in the first meiotic division of a normal male (a proof not previously provided by human cases of XXY, which could have been of different origin). However, first-meiotic nondisjunction is apparently very rare in males, and there is not yet any evidence that it ever occurs in females. Data from numerous types of crosses involving five sex-linked markers yield the following results: no cases of X(M)X(M)Y or OX(P) have occurred to date; X(M)X(P)Y << X(M)O; OX(P) << X(M)O (where the superscripts M and P designate maternal and paternal derivation, respectively, of the X). The total frequency of XO individuals can be increased by irradiation shortly after fertilization. This treatment has yielded, in addition to X(M)O, several animals of the OX(P) constitution, a type that has not yet been found to occur spontaneously. The various findings on spontaneous and induced frequencies of mice with abnormal numbers of sex chromosomes lead to the conclusion that XO individuals are most often the result of events occurring after fertilization. Specifically, it is suggested that there exists a relatively high probability of loss of the paternally contributed sex chromosome some time between fertilization and the first cleavage(32).

Reversal of an ancient sex chromosome to an autosome in Drosophila

Abstract: Although transitions of sex-determination mechanisms are frequent in species with homomorphic sex chromosomes, heteromorphic sex chromosomes are thought to represent a terminal evolutionary stage owing to chromosome-specific adaptations such as dosage compensation or an accumulation of sex-specific mutations. Here we show that an autosome of Drosophila, the dot chromosome, was ancestrally a differentiated X chromosome. We analyse the whole genome of true fruitflies (Tephritidae), flesh flies (Sarcophagidae) and soldier flies (Stratiomyidae) to show that genes located on the dot chromosome of Drosophila are X-linked in outgroup species, whereas Drosophila X-linked genes are autosomal. We date this chromosomal transition to early drosophilid evolution by sequencing the genome of other Drosophilidae. Our results reveal several puzzling aspects of Drosophila dot chromosome biology to be possible remnants of its former life as a sex chromosome, such as its minor feminizing role in sex determination or its targeting by a chromosome-specific regulatory mechanism. We also show that patterns of biased gene expression of the dot chromosome during early embryogenesis, oogenesis and spermatogenesis resemble that of the current X chromosome. Thus, although sex chromosomes are not necessarily evolutionary end points and can revert back to an autosomal inheritance, the highly specialized genome architecture of this former X chromosome suggests that severe fitness costs must be overcome for such a turnover to occur.

Male-specific lethal 2, a dosage compensation gene of Drosophila, undergoes sex-specific regulation and encodes a protein with a RING finger and a metallothionein-like cysteine cluster.

Abstract: In Drosophila the equalization of X-linked gene products between males and females, i.e. dosage compensation, is the result of a 2-fold hypertranscription of most of these genes in males. At least four regulatory genes are required for this process. Three of these genes, maleless (mle), male-specific lethal 1 (msl-1) and male-specific lethal 3 (msl-3), have been cloned and their products have been shown to interact and to bind to numerous sites on the X chromosome of males, but not of females. Although binding to the X chromosome is negatively correlated with the function of the master regulatory gene Sex lethal (Sxl), the mechanisms that restrict this binding to males and to the X chromosome are not yet understood. We have cloned the last of the known autosomal genes involved in dosage compensation, male-specific lethal 2 (msl-2), and characterized its product. The encoded protein (MSL-2) consists of 769 amino acid residues and has a RING finger (C3HC4 zinc finger) and a metallothionein-like domain with eight conserved and two non-conserved cysteines. In addition, it contains a positively and a negatively charged amino acid residue cluster and a coiled coil domain that may be involved in protein-protein interactions. Males produce a msl-2 transcript that is shorter than in females, due to differential splicing of an intron of 132 bases in the untranslated leader. Using an antiserum against MSL-2 we have shown that the protein is expressed at a detectable level only in males, where it is physically associated with the X chromosome. Our observations suggest that MSL-2 may be the target of the master regulatory gene Sxl and provide the basic elements of a working hypothesis on the function of MSL-2 in mediating the 2-fold increase in transcription that is characteristic of dosage compensation.