12. G E N E T I C C Y T O L O G Y
449
Cytologically, it is not possible to determine which X is maternal
and which is paternal unless a morphological marking can be introduced into one of them. Genetic evidence compiled by Lyon (1961),
however, seems to indicate that either may be inactivated, and different
cells may have different inactivation patterns. Lyon's examples consist
mainly of sex-linked mutants of the mouse that affect coat color. In
females heterozygous for coat-color genes, the phenotype is known to
be mottled or dappled, with patches of normal and mutant colors. She
interpreted this mosaic phenotype as the effect of inactivation of one
or the other X chromosome early in embryonic life. If, in one primordial
pigment cell, the X chromosome carrying the dominant coat-color gene
is inactivated, its descendents will bear the same inactivated X , and the
recessive mutant color will manifest as if it were a homozygote; and
if, in another area, the X chromosome carrying the mutant gene
becomes inactivated, the dominant gene expresses. The situation is
analogous to the V-type position effect described in the preceding section, except that there is no rearrangement present. Lyon actually
extends her thesis to predict that all sex-linked genes of the mouse
should behave the same way, but only those with localized phenotype,
such as coat color or hair structure, will show a mosaic appearance.
When phenotype is not locally involved, various responses will result.
These include intermediate phenotype, incomplete penetrance, or
even complete suppression of the expression of the mutant gene by that
of the normal allele. More recently, even biochemical traits have been
found to follow the same principle (Beutler, Yeh and Fairbanks, 1962).
I must admit that Lyon's theory inspired me to design experiments
with H
3 - U R . The behavior of the sex chromatin in female mammalian
cells is almost identical with that of the heterochromatin in Drosophila.
Actually V-type variegation does occur in this system (Russell and
Bangham, 1959; Cattanach, 1961; Russell, 1961). Variegation in
heterozygotes for autosomal genes has been found in the mouse only
when a dominant gene is translocated to the X chromosome, and only
when two X chromosomes ( X X or X X Y ) are present. The same translocation in individuals with a single X ( X Y or X O ) exhibits no such
activity. Based on her tremendous amount of genetic evidence, Russell
derived a theory of heterochromatinlike action of one X in the female
mouse, a theory quite similar to Lyon's. Mosaic expression of the alleles
again indicates that either X can be inactivated. Since translocations
do not occur in the same neighborhood of a chromosome, the variegation effect also suggests that an entire X becomes inactivated rather
than a specific region.
Cytologically, one can only observe the sex chromatin. If the two
minute parts of a sex chromatin represent the two arms of an X chromoQ
449
Cytologically, it is not possible to determine which X is maternal
and which is paternal unless a morphological marking can be introduced into one of them. Genetic evidence compiled by Lyon (1961),
however, seems to indicate that either may be inactivated, and different
cells may have different inactivation patterns. Lyon's examples consist
mainly of sex-linked mutants of the mouse that affect coat color. In
females heterozygous for coat-color genes, the phenotype is known to
be mottled or dappled, with patches of normal and mutant colors. She
interpreted this mosaic phenotype as the effect of inactivation of one
or the other X chromosome early in embryonic life. If, in one primordial
pigment cell, the X chromosome carrying the dominant coat-color gene
is inactivated, its descendents will bear the same inactivated X , and the
recessive mutant color will manifest as if it were a homozygote; and
if, in another area, the X chromosome carrying the mutant gene
becomes inactivated, the dominant gene expresses. The situation is
analogous to the V-type position effect described in the preceding section, except that there is no rearrangement present. Lyon actually
extends her thesis to predict that all sex-linked genes of the mouse
should behave the same way, but only those with localized phenotype,
such as coat color or hair structure, will show a mosaic appearance.
When phenotype is not locally involved, various responses will result.
These include intermediate phenotype, incomplete penetrance, or
even complete suppression of the expression of the mutant gene by that
of the normal allele. More recently, even biochemical traits have been
found to follow the same principle (Beutler, Yeh and Fairbanks, 1962).
I must admit that Lyon's theory inspired me to design experiments
with H
3 - U R . The behavior of the sex chromatin in female mammalian
cells is almost identical with that of the heterochromatin in Drosophila.
Actually V-type variegation does occur in this system (Russell and
Bangham, 1959; Cattanach, 1961; Russell, 1961). Variegation in
heterozygotes for autosomal genes has been found in the mouse only
when a dominant gene is translocated to the X chromosome, and only
when two X chromosomes ( X X or X X Y ) are present. The same translocation in individuals with a single X ( X Y or X O ) exhibits no such
activity. Based on her tremendous amount of genetic evidence, Russell
derived a theory of heterochromatinlike action of one X in the female
mouse, a theory quite similar to Lyon's. Mosaic expression of the alleles
again indicates that either X can be inactivated. Since translocations
do not occur in the same neighborhood of a chromosome, the variegation effect also suggests that an entire X becomes inactivated rather
than a specific region.
Cytologically, one can only observe the sex chromatin. If the two
minute parts of a sex chromatin represent the two arms of an X chromoQ