RANDOM X inactivation makes the female mammal a natural mosaic for clones of cells having either the maternally derived X (Xm) or paternally derived one (Xp) which is genetically inactive1. There are, however, instances in which inactivation is obviously not random2–7. Non-randomness was inferred from studies made on differentiated cells remote from early embryonic cells in which inactivation occurred. Thus it is not clear whether the randomness of the X inactivation process was influenced or whether cell selection occurring after random inactivation was responsible for the ultimate non-random appearance4–9. In an effort to determine the embryonic stage at which the X chromosome initiates differentiation in famale mouse embryos heterozygous for Cattanach's translocaton10, we found that the mosaic composition was consistently biased in extraembryonic membranes, whereas it was not necessarily so in the embryonic body.

Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse

Publisher Summary This chapter discusses many observations indicating a decline in immune function with aging both in experimental animals and in humans. It is evident that a decline in T cell function gradually occurs and this affects the entire immune system. Antibody formation and B cell function appear to be secondarily altered. Various autoantibodies are increased in older experimental animals and humans that may relate to the observed decrease in suppressor cells. Cell-mediated immunity has been analyzed in vivo and in vitro. Various T cell-dependent functions decline with age. Normal immune functions can begin to decline as early as when an individual reaches sexual maturity. The decline is due to changes in the immune cells and their milieu. Cell loss, shift in the proportion of subpopulations, and qualitative cellular changes, the three possible types of changes that can cause the decline, have all been detected.

Age influence on the immune system.

Summary

1. The review considers information from mammalian embryology relevant to X-chromosome inactivation, and from X-inactivation relevant to mammalian embryology.



2. Properties of the inactive-X, by which it may be recognized are: sex chromatin, heteropycnosis, late replication and the absence of gene product. Each of these has advantages and disadvantages in particular circumstances. In some species the X carries constitutive heterochromatin, which must be distinguished from the facultative region.



3. The time of X-chromosome inactivation can be estimated from the time of appearance of sex chromatin or late replication, or inferred from the appearance of heterozygotes for X-linked genes or of experimental chimaeras. The estimated time varies with species, and in the mouse and rabbit is near the time of increase in RNA synthesis.



4. Whereas in eutherian mammals either the maternally or the paternally derived X may be inactivated in different cell lines, in marsupials the paternal X is always the inactive one.



5. During development various factors act to distort the patterns produced by random X-inactivation. These factors include cell selection, transfer of gene product, and migration and mingling of cells.



6. There is no clear evidence that X-chromosome inactivation is not complete.



7. In female germ cells both X-chromosomes appear to be active. In male ones both X and Y appear inactive during most of spermatogenesis, although probably in early stages all X chromosomes present are active.



8. The active and inactive X-chromosomes may be differentiated by presence or absence of some non-histone protein or other polyanionic substance.



9. If the genes concerned in synthesis or attachment of this substance are on the X-chromosome then the differentiation will be self-maintaining.



10. The initiation of the differentiation requires either the attachment of different X-chromosomes to different sites, or some interaction of X-linked and autosomal genes, concerned in inducing or repressing activity. Some possible models are discussed.

X-chromosome inactivation and developmental patterns in mammals

Cytoplasmic inheritance and intragenomic conflict

EUKARYOTIC cells contain a class of cytoplasmic DNA molecules which are found only within the mitochondria, where they replicate and are transcribed (for a general review see ref. 1). This mitochondrial DNA (mtDNA) constitutes the ‘mitochondrial genome’ and carries genetic information essential to mitochondrial function. In view of its extranuclear location, it is not surprising that inheritance of the mitochondrial genome is not governed by the same rules that apply to chromosomal genes. For fungi2–7 and amphibians8 there is evidence that the mitochondrial genome of an individual is derived solely from the maternal parent (in contrast to chromosomal genes, which are inherited biparentally). We present here evidence that the mitochondrial genome is inherited maternally in mammals too.

Maternal inheritance of mammalian mitochondrial DNA

Chromosome Investigations of a Small Isolated Human Population: Chromosome Abnormalities and Distribution of Chromosome Counts According to Age and Sex Among the Population of Tristan Da Cunha

Chromosome investigations of a small isolated human population: chromosome abnormalities and distribution of chromosome counts according to age and sex among the population of Tristan da Cunha.

One mammalian X chromosome in females and the Y chromosome in males are heterochromatic, and they seem to carry “controlling centers” which affect both sex determination and various somatic characters. The euchromatic X chromosome may carry the structural genes for testicular as well as ovarian determination, the former only functioning in the presence of a Y chromosome or suitable autosomal modifier.

Significance of sex chromosome derived heterochromatin in mammals.

The study of a bovine freemartin and its male co-twin has shown that the sex-reversed gonads of the female are secreting testosterone. Therefore, we suggest that the masculinisation of the freemartin’

Cytogenetic and endocrine studies of a freemartin heifer and its bull co-twin

Evidence that the Xg blood group genes are on the short arm of the X chromosome.

THE mule (2n=63) is a hybrid between a jack donkey (Equus asinus, 2n=62) and a mare (E. caballus, 2n=64). The two chromosome complements are quite distinct, and in particular the X chromosomes differ morphologically; the donkey X (XD) is submetacentric and the horse X (XH) is metacentric (Fig. 1). It has also been shown that the glucose-6-phosphate dehydrogenase (G6PD) locus is X-linked in both1,2. The electrophoretic phenotype consists of a fast and slow band in both species, the G6PD of the donkey moving faster than the G6PD of the horse (Fig. 2). If one of the X chromosomes in the female mule is inactivated at random and if this inactivation can be recognized by a delay in its DNA synthesis3–5, then about 50 per cent of cells should show a late replicating XH and 50 per cent a late replicating XD. Furthermore, the G6PD pattern in the mule should consist of three bands, a fast G6PD-donkey, a mixed intermediate band corresponding to the slow G6PD-donkey plus the fast G6PD-horse and finally a slow G6PD-horse (Fig. 2).

J. L. Hamerton

Papers

Chromosome investigations of a small isolated human population: chromosome abnormalities and distribution of chromosome counts according to age and sex among the population of Tristan da Cunha.

Significance of sex chromosome derived heterochromatin in mammals.

Cytogenetic and endocrine studies of a freemartin heifer and its bull co-twin

Evidence that the Xg blood group genes are on the short arm of the X chromosome.

Non-random X -Inactivation in the Female Mule