1. A second practice problem set (with answers) is on the course website.
The review session for the second midterm
is on Thursday evening, April 10, from 7-9pm
in ROOM 141 GIANNINI HALL

2. GSD: genotypic sex determination
onwards with:
GSD: genotypic sex determination
Segregation of alleles (genes) determines sex
best for generating 1:1 sex ratios
Amazing variety of mechanisms
(sex determination & sexual dimorphism is
the most rapidly evolving aspect of developmental programming)

3. For fruit flies:
XX (±Y) females X(±Y) males
What about X-chromosome number matters?
absolute number: 1=male, 2or more = female
odd vs. even (paired?)
XX X=male?
number relative to ploidy (non-sex chromosomes)?
X AA male, but X A female?
X:A ratio
…again, genetic exceptions to the rule provide the answer

4. XXX AAA X:A= 1, female (jumbo)
For fruit flies:
X(±Y) AA X:A = 0.5, male
XX(±Y) AA X:A = 1, female
Progeny from
Bridges' "exceptional" female:
XXX AAA X:A= 1, female (jumbo)
XX(±Y) AAA X:A = 0.67, intersex (phenotypic mosaic)
X A X:A=1,
What about:
how could he know???
(dead)
female

5. GENETIC MOSAICS revealed the sex of X A cells
(nonmosaic XA animals never reach the sexually dimorphic (adult) stage)
XX AA zygote -->
XXAA cells / X AA cells
recall that:
X-chromosome loss generates
“gynandromorphs”
XXAA zygote -->
XXAA cells/XA cells
(loss of an entire haploid set)
(XXAA)
Female
(X A)
(XXAA)
Female
(X AA)
Male
(genetic "markers"
allowed him to infer
the genotypes)

6. GSD by X:A ratio (balance)
X AA X:A = 0.5, male
XX AA X:A = 1, female
XX(±Y) AAA X:A = 0.67, intersex
XXX AAA X:A= 1, female (large)
X A X:A=1,
(dead) female
GSD by X:A ratio (balance)

7. GSD by X:A ratio (balance)
Balance between what?
What is it about ploidy changes that affects the way that
X-chromosome dose determines sex?
"Obviously": female-determining genes on the X
and
male-determining genes on the autosomes
"numerator genes"
"denominator genes" :

8. Fig. 18.21 …but what else could it be? (your text fudges whether
Obviously:
female-determining genes on the X
("numerator genes")
and
male-determining genes on the autosomes
("denominator genes")
Pure speculation
on Bridges' part
(1921)
…but what else could it be?
speculation turned into
textbook "fact"
(your text fudges whether
hypothesis vs. fact but many other
texts present it as fact)

9. Fig. 18.21 O.K. 1921 2007 not O.K. vs. maternal gene products finally
and not what Bridge's guessed
or what the textbooks say)
Obviously:
female-determining genes on the X
("numerator genes")
and
male-determining genes on the autosomes
("denominator genes")
O.K.
not O.K.
finally
the answer!
female-determining genes on X exist
(including the master, Sxl)
vs.
maternal gene products
…and
alters the
TIME of counting by Sxl
and hence the concentration
of the relevant female-determining gene products
ploidy

10. The (round) worm (Caenorhabditis elegans):
XX self-fertilizing hermaphrodite
mostly more
hermaphrodites
XO male (heterogametic sex)
Two ways to get males:
(1) Spontaneous X-chromosome nondisjunction (rare)
to make “O” eggs in the hermaphrodite
(+ X self sperm)-> XO male
(2) Mating (outcross) of hermaphrodite to XO male:
X eggs join with X or O male sperm -> 50:50

11. Worm X-chromosome counting is somewhat like that in the fly,
but different in important ways:
XX self-fertilizing hermaphrodite
XO male (heterogametic sex)
XX AAA X:A= 0.67 = male (not a mosaic)
XXX AAAA X:A = 0.75 = hermaphrodite
again: GSD by X:A ratio
…and there do appear to be "male-determining
genes on the autosomes against which
"hermaphrodite-determining genes on X" are measured

12. is a remarkably rare sex-determination mechanism
GSD by X:A ratio
is a remarkably rare sex-determination mechanism
among species

13. dominant masculinizer
HUMANS:
XX female XY male
XXY Kleinfelter Syndrome
sterile male (1:1000 men)
XO Turner Syndrome
sterile female (1: )
GSD by Active Y
dominant masculinizer

14. GSD by dominant masculinizing allele M
HOUSE FLIES:
m/m female M/m male
GSD by dominant masculinizing allele M
(no heteromorphic sex chromosomes)
(…actually, only one of three different GSD systems
that operate in different races of the same species!)

15. GSD by feminizing W or Z:A ?
Birds, moths and butterflies:
ZZ male ZW female
female is
the heterogametic sex
(compare: XY males)
GSD by feminizing W or Z:A ?

16. But is the relevant variable ploidy?
>>20% of all animals use a very different GSD system:
Eggs fertilized --> Queens (females) or workers (sterile)
Diploid (± royal jelly)
Eggs not fertilized --> Drones (males)
Haploid
GSD by “haplodiploid” system
But is the relevant variable ploidy?

17. GSD by a multiple allele system
Let’s encourage inbreeding (incest) among the honeybees:
increased homozygosity
suddenly: DIPLOID MALES!
a1/a2 Queen X a1 Drone --> a1/a1 & a2/a1 & a1 & a2
diploid
drones
(fertilization)
workers
& queens
haploid
(perhaps
her brother)
a1 or a1/a1 hemizygotes and homozygotes: males
a2 or a2/a2
a1/a2 heterozygotes: females (queens and workers)
GSD by a multiple allele system
--- highly “polymorphic” sex gene (many alleles)

18. GSD via a Maternal Effect system:
(for a blowfly)
Genotype of mother
determines (or at least influences) the
Phenotype of the progeny
f / f X
males
Female-producing mothers
Male-producing mothers
F / f
f / f
f / f sons
1:1
sex ratio
f / f X
males
F / f & f / f
daughters

19. hence: males are monosomic for 1/5 of their genome males are monosomic
A potential problem with many GSD systems (including our own): XX AA XY
female
male
fruit flies:
honeybees: AA A
female
male
NO PROBLEM
PROBLEM
fact: gene output is generally proportional to gene dose in metazoans
fact: 20% of all fly genes are on X
few of these are on fly Y
hence: males are monosomic
for 1/5 of their genome
males are monosomic
for entire genome
haploid
(even 1% is rarely tolerated)
not genetically
unbalanced
potentially genetically unbalanced

20. XX XY How eliminate the anticipated X-linked gene expression
difference between the sexes?
= X-chromosome dosage compensation
(1) increase X-linked gene expression 2x in males
fruit flies (“the fly”)
(2) decrease X-linked gene expression in females by 1/2
2a: reduce each X by 50%
the worm
2b: inactivate one X
us mammals

21. o + o wa/wa = (same color as) wa/Y
Recall that Muller observed X-linked gene dose effect within a sex,
but not between the sexes
wa/wa > (darker, more “wildtype”) wa/Df(w)
(or wa/w-)
> o +
wa/Y < (lighter, less “wildtype”) wa/Y; Dp(wa)/+ o
YET:
wa/wa = (same color as) wa/Y
“leaky” (hypomorphic) mutant alleles twice as leaky in males vs. females
wa/Y; Dp(wa)/+
> (darker, more “wildtype”)
wa/wa
It must follow that:
Infer: wildtype alleles twice as active in males vs. females to achieve balance

22. XY XX wildtype (normal) X-linked alleles work twice as hard in males
as they do in females
= X-chromosome dosage compensation XX XY
Are the male genes working twice as hard, or instead are the
female genes working half as hard? (is the glass half full or half empty)
Can actually answer the question.
But first:
Are the alleles on both the female’s X chromosomes even working?
YES

23. w+/w- Muller knew from gynandromorphs: white gene functioning is
“cell autonomous”:
(XXAA)
Female
(X AA)
Male
Gynandromorph:
w+/w- w-
a cell’s phenotype reflects
its genotype with respect
to the particular gene
w+/w-
non-mosaic eye is solid red,
not mosaic red and white
…alleles on both X’s must be active

24. Are male X-linked genes turned UP or are
female X-linked genes turned DOWN?