General Genetics
Ayesha M. Khan
Spring 2013
Sex Determination in Drosophila
 The fruit fly Drosophila melanogaster, has eight chromosomes:
three pairs of autosomes and one pair of sex chromosomes
 Presence of the Y chromosome does not determine maleness in
Drosophila
 Each fly’s sex is determined by a balance between genes on the
autosomes and genes on the X chromosome. This type of sex
determination is called the genic balance system.
 The X chromosome contains genes with female producing
effects, whereas the autosomes contain genes with maleproducing effects.
 Fly’s sex is determined by the X:A ratio, the number of X
chromosomes divided by the number of haploid sets of
autosomal chromosomes.
Sex Determination in Drosophila
An X:A ratio of 1.0 produces a female fly; an X:A ratio
of 0.5 produces a male.
 X:A ratio less than 0.5: a male phenotype is produced,
but the fly is weak and sterile—metamales.
 X:A ratio between 1.0 and 0.50: intersex fly, with a
mixture of male and female characteristics.
 X:A ratio > than 1.0 : Female phenotype is produced, but
these flies (called metafemales) have serious
developmental problems and many never emerge from
the pupal case.
Chromosome complements and sexual phenotypes in Drosophila
Sex Determination in Humans
• XX-XY sex determination
• Presence of a gene on the Y chromosome
determines maleness
• Turner syndrome: XO; 1/3000 female births
– Immature secondary sex characteristics
– Normal intelligence
– Sterile
• Klinefelter syndrome: XXY, or XXXY, or XXXXY, or XXYY;
1/1000 male births
– Immature secondary sex characteristics
– Most have normal intelligence
– Sterile
• Poly-X females: 1/1000 female births
– Normally regular secondary sex characteristics
– Fertile
– Mental retardation slightly higher
The role of sex chromosomes
• The X chromosome contains genetic
information essential for both sexes; at least
one copy of an X chromosome is required for
human development.
• The male-determining gene is located on the
Y chromosome. A single copy of this
chromosome, even in the presence of several
X chromosomes, produces a male phenotype.
The role of sex chromosomes (contd)
• The absence of the Y chromosome results in a
female phenotype.
• Genes affecting fertility are located on the X and
Y chromosomes. A female usually needs at least
two copies of the X chromosome to be fertile.
• Additional copies of the X chromosome may
upset normal development in both males and
females, producing physical and mental problems
that increase as the number of extra X
chromosomes increases.
The male-determining gene in humans
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David Page (1987)
Analyzed the chromosomes of sex-reversed
XX men, rare individuals who look like men
but have two X chromosomes instead of
one X chromosome and one Y chromosome.
Page discovered that sex-reversed males
carried genes from a 140-kilobase region on
the short arm of the Y chromosome.
Presumably, this region had been transferred
to the X chromosome during a translocation.
Subsequent experiments narrowed down
this region and found that one gene, the sexdetermining region of the Y, or SRY was the
master regulator of sex determination. The
presence of just this region from the Y
chromosome is thus sufficient to cause
male development .
The SRY Gene
How the Y chromosome determines sex:
• The SRY gene, located on the Y chromosome, is the primary
determinant of sexual development.
– That is, if a developing embryo has a functional SRY gene
in its cells, it will develop as a male. And, if there is no
functional SRY, the embryo develops as female.
• Although the SRY gene is usually on the Y chromosome, it
occasionally gets transferred to the X.
– this leads to 46,XX males
• Also, sometimes the SRY gene is inactivated by mutation.
– Leading to 46,XY females (Swyer syndrome)
– it is also possible to have a partially inactive SRY gene
Androgen-insensitivity syndrome
-Females; X and Y chromosome
-Caused by the defective androgen
receptor; cells are insensitive to
testosterone, and female characteristics
develop.
-The gene for the androgen receptor is
located on the X chromosome; so persons
with this condition always inherit it from
their mothers.
Sex-linked characteristics
Sex-Linked Characteristics Are Determined by
Genes on the Sex Chromosomes
• Genes on the X chromosome determine Xlinked characteristics; those on the Y
chromosome determine Y-linked
characteristics.
Thomas Morgan
(1866-1945)
The first person to explain sexlinked inheritance was the
American biologist Thomas Hunt
Morgan
X-Linked White Eyes in Drosophila
In both humans and fruit flies
(Drosophila melanogaster) females have
two X chromosomes, while males have
X and Y
Sex Linkage
Morgan (1910) found a mutant white-eyed male fly, and used it in
a series of experiments that showed a gene for eye color located
on the X chromosome.
a. First, he crossed the white-eyed male with a wild-type (red-eyed)
female. All F1 flies had red eyes. Therefore, the white-eyed trait is
recessive.
b. Next, F1 were interbred. They produced an F2 with:
i. 3,470 red-eyed flies.
ii. 782 white-eyed flies.
c. All of the F2 white-eyed flies were male.
X-linked inheritance of white eyes in Drosophila: Red-eyed female  white-eyed male
X-linked inheritance of white
eyes in Drosophila:
The F1 flies are interbred to
produce the F2
=>This finding was clearly
not the expected result
for a simple recessive
trait,
which
should
appear in ¼ of both male
and female F2 offspring.
What happened when white eyed males and
red eyed females from second generation were
crossed?
=>Equal number of offspring with each eye color
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Morgan’s hypothesis was that this eye color
gene is located on the X chromosome.
Males therefore cannot be either homozygous or
heterozygous but are said to be hemizygous for
X-linked loci.
-Females may be homozygous or heterozygous.
The wild-type female in the original cross was
w+/w+ (homozygous for red eyes).
-Females only show the white eyes trait if they
inherit mutant genes on both X chromosomes.
“Sex-linked inheritance”
Reciprocal cross: Homozygous white-eyed female  red-eyed ( wild-type) male
Reciprocal cross: The F1 flies are interbred to produce the F2
Morgan’s discovery of X-linked inheritance
showed that when results of reciprocal
crosses are different, and ratios differ
between progeny of different sexes, the
gene involved is likely to be X-linked (sexlinked).
This was strong evidence that genes are
located on chromosomes.
Morgan received the 1933 Nobel Prize for
Physiology or Medicine for this work.
Non-Disjunction of X Chromosomes
1. Morgan’s work showed that crossing a white-eyed female (w/w)
with a red-eyed male (w+/Y) produces an F1 of white-eyed males
(w/Y) and red-eyed females (w+/w). His student, Bridges, found
that about 1 in 2,000 of the offspring was an exception, either a
white-eyed female or red-eyed male.
2. Bridges’ hypothesis was that chromatids failed to separate
normally during anaphase of meiosis I or II, resulting in nondisjunction.
3. Non-disjunction can involve either autosomes or sex
chromosomes. For the eye-color trait, X chromosome nondisjunction was the relevant event. Non-disjunction in an
individual with a normal set of chromosomes is called primary
non-disjunction.
Nondisjunction in meiosis involving the X chromosome