A second practice problem set with answers is

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 -9 pm in ROOM 141 GIANNINI HALL

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)

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

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) What about: XA X: A=1, (dead) female how could he know? ? ?

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

X AA X: A = 0. 5, male XX AA XX(±Y) AAA X: A = 1, female X: A = 0. 67, intersex XXX AAA X: A= 1, female (large) XA X: A=1, (dead) female GSD by X: A ratio (balance)

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"

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" Fig. 18. 21 (your text fudges whether hypothesis vs. fact but many other texts present it as fact)

Fig. 18. 21 Obviously: female-determining genes on the X ("numerator genes") O. K. and male-determining genes on the autosomes not O. K. ("denominator genes") 1921 2007 thefinally answer! and not what Bridge's guessed or what the textbooks say) female-determining genes on X exist (including the master, Sxl) vs. maternal gene products …and ploidy alters the TIME of counting by Sxl and hence the concentration of the relevant female-determining gene products

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

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

GSD by X: A ratio is 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 Y dominant 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 systems that operate in different races of the same species!)

Birds, moths and butterflies: ZZ male ZW female is the 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) Diploid (± royal jelly) Eggs not fertilized --> Drones (males) Haploid GSD by “haplodiploid” system But is the relevant variable ploidy?

Let’s encourage inbreeding (incest) among the honeybees: increased homozygosity suddenly: DIPLOID MALES! (fertilization) a 1/a 2 Queen X a 1 Drone --> a 1/a 1 & a 2/a 1 & a 2 diploid haploid diploid (perhaps workers her brother) drones & queens a 1/a 2 heterozygotes: females (queens and workers) a 1 or a 1/a 1 hemizygotes and homozygotes: males a 2 or a 2/a 2 GSD by a multiple allele system --- highly “polymorphic” sex gene (many alleles)

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

A potential problem with many GSD systems (including our own): fruit flies: honeybees: XX AA XY AA female PROBLEM AA female A male NO 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 (even 1% is rarely tolerated) potentially genetically unbalanced males are monosomic haploid for entire genome not genetically unbalanced

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

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

wildtype (normal) X-linked alleles work twice as hard in males as they do in females XX XY = X-chromosome dosage compensation 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

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

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