A second practice problem set(with answers)

is on the course website.

The review session for the second midtermis on Thursday evening, April 10, from 7-9pm

in ROOM 141 GIANNINI HALL

GSD: genotypic sex determination

Segregation of alleles (genes) determines sex

best for generating 1:1 sex ratios

onwards with:

Amazing variety of mechanisms(sex determination & sexual dimorphism is

the most rapidly evolving aspect of developmental programming)

XX (±Y) females X(±Y) males

What about X-chromosome number matters?

…again, genetic exceptions to the rule provide the answer

For fruit flies:

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

XX(±Y) AA X:A = 1, female

X(±Y) AA X:A = 0.5, male

XX(±Y) AAA X:A = 0.67, intersex (phenotypic mosaic)

XXX AAA X:A= 1, female (jumbo)

(dead)

For fruit flies:

Bridges' "exceptional" female:

female

Progeny from

X A X:A=1,

What about:

how could he know???

XX AA zygote --> XXAA cells / X AA cells

recall that:X-chromosome loss generates “gynandromorphs”

GENETIC MOSAICS revealed the sex of X A cells(nonmosaic XA animals never reach the sexually dimorphic (adult) stage)

(XXAA)

Female(X AA) Male

(XXAA)

Female(X A) Female

XXAA zygote -->XXAA cells/XA cells(loss of an entire haploid set)

(genetic "markers"allowed him to infer

the genotypes)

XX AA X:A = 1, female

X AA X:A = 0.5, male

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)

GSD by X:A ratio (balance)

What is it about ploidy changes that affects the way thatX-chromosome dose determines sex?

"Obviously": female-determining genes on the Xand

male-determining genes on the autosomes

Balance between what?

"numerator genes" "denominator genes":

Obviously:

female-determining genes on the X("numerator genes")and male-determining genes on the autosomes("denominator genes")

Pure speculationon Bridges' part

(1921)

…but what else could it be?

speculation turned intotextbook "fact"

Fig. 18.21(your text fudges whether

hypothesis vs. fact but many othertexts present it as fact)

Obviously:

female-determining genes on the X("numerator genes")and male-determining genes on the autosomes("denominator genes")

1921 2007

Fig. 18.21

vs.maternal gene products

…and alters the

TIME of counting by Sxland hence the concentration

of the relevant female-determining gene products

and not what Bridge's guessed or what the textbooks say)

female-determining genes on X exist(including the master, Sxl)

O.K.

not O.K.

finallythe answer!

ploidy

The (round) worm (Caenorhabditis elegans):

XX self-fertilizing hermaphrodite

XO male (heterogametic sex)

(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

Two ways to get males:

mostly morehermaphrodites

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-determininggenes on the autosomes against which

"hermaphrodite-determining genes on X" are measured

GSD by X:A ratiois a remarkably rare sex-determination mechanism

among species

HUMANS:

XX female XY male

XXY Kleinfelter Syndrome

sterile male (1:1000 men)

XO Turner Syndrome

sterile female (1:2000-5000)

GSD by Active Ydominant masculinizer

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 systemsthat operate in different races of the same species!)

Birds, moths and butterflies:

ZZ male ZW female

female isthe heterogametic sex

(compare: XY males)

GSD by feminizing W or Z:A ?

>>20% of all animals use a very different GSD system:

Eggs fertilized --> Queens (females) or workers (sterile)

Eggs not fertilized --> Drones (males)

Diploid (± royal jelly)

Haploid

GSD by “haplodiploid” system

But is the relevant variable ploidy?

Let’s encourage inbreeding (incest) among the honeybees:

suddenly: DIPLOID MALES!

GSD by a multiple allele system--- highly “polymorphic” sex gene (many alleles)

increased homozygosity

a1 or a1/a1 hemizygotes and homozygotes: malesa2 or a2/a2

a1/a2 heterozygotes: females (queens and workers)

a1/a2 Queen X a1 Drone --> a1/a1 & a2/a1 & a1 & a2

diploiddrones

(fertilization)

diploidworkers

& queens

haploiddrones

(perhapsher brother)

GSD via a Maternal Effect system:

(for a blowfly)

Female-producing mothers

Male-producing mothers

F / f

f / f

F / f & f / f daughters

f / f sons 1:1sex ratio

Genotype of mother

determines (or at least influences) thePhenotype of the progeny

f / fX males

f / fX males

A potential problem with many GSD systems (including our own):

XXAA

XYAA

female male

fruit flies: honeybees:

AA A

female male

fact: 20% of all fly genes are on Xfew of these are on fly Y

hence: males are monosomic for 1/5 of their genome

males are monosomic for entire genomehaploid

PROBLEM NO PROBLEM

(even 1% is rarely tolerated)

potentially genetically unbalancednot genetically unbalanced

fact: gene output is generally proportional to gene dose in metazoans

How eliminate the anticipated X-linked gene expressiondifference between the sexes?

(1) increase X-linked gene expression 2x in males

(2) decrease X-linked gene expression in females by 1/2

= X-chromosome dosage compensation

2a: reduce each X by 50%

2b: inactivate one X

fruit flies (“the fly”)

the worm

us mammals

XX XY

wa/wa = (same color as) wa/Y

YET:

Recall that Muller observed X-linked gene dose effect within a sex,but not between the sexes

wa/Y; Dp(wa)/+ > (darker, more “wildtype”) wa/wa

It must follow that:

wa/wa > (darker, more “wildtype”) wa/Df(w)(or wa/w-)>

o+

wa/Y < (lighter, less “wildtype”) wa/Y; Dp(wa)/+o

“leaky” (hypomorphic) mutant alleles twice as leaky in males vs. females

Infer: wildtype alleles twice as active in males vs. females to achieve balance

wildtype (normal) X-linked alleleswork twice as hard in males

as they do in females

= X-chromosome dosage compensationXX XY

Are the male genes working twice as hard, or instead are thefemale genes working half as hard? (is the glass half full or half empty)

Are the alleles on both the female’s X chromosomes even working?

YES

Can actually answer the question.

But first:

Muller knew from gynandromorphs: white gene functioning is“cell autonomous”:

a cell’s phenotype reflectsits genotype with respect

to the particular gene

w+/w- non-mosaic eye is solid red,not mosaic red and white

(XXAA)

Female(X AA) Male

Gynandromorph:

w+/w- w-

…alleles on both X’s must be active

Are male X-linked genes turned UPor are

female X-linked genes turned DOWN?