A second practice problem set (with answers) is on the course website.

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. 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. absolute number: 1=male, 2or 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? For fruit flies: XX (±Y) femalesX(±Y) males What about X-chromosome number matters? …again, genetic exceptions to the rule provide the answer

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

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

6. 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. : "numerator genes" "denominator genes" 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

8. Fig. 18.21 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. not O.K. 1921 2007 and not what Bridge's guessed or what the textbooks say) female-determining genes on X exist (including the master, Sxl) Fig. 18.21 Obviously: female-determining genes on the X ("numerator genes") and male-determining genes on the autosomes ("denominator genes") O.K. finally the answer! 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. mostly more hermaphrodites (2) Mating (outcross) of hermaphrodite to XOmale: X eggs join with X or O male sperm -> 50:50 The (round) worm (Caenorhabditis elegans): XX self-fertilizing hermaphrodite 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

11. XX self-fertilizing hermaphrodite XO male (heterogametic sex) Worm X-chromosome counting is somewhat like that in the fly, but different in important ways: 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. GSD by X:A ratio is a remarkably rare sex-determination mechanism among species

13. HUMANS: XX femaleXY male XXY Kleinfelter Syndrome sterile male (1:1000 men) XO Turner Syndrome sterile female (1:2000-5000) GSD by Active Y dominant masculinizer

14. HOUSE FLIES: m/m femaleM/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. female is the heterogametic sex (compare: XY males) Birds, moths and butterflies: ZZ maleZW female GSD by feminizing W or Z:A ?

16. >>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. increased homozygosity (fertilization) a1/a2 Queen X a1 Drone --> a1/a1& a2/a1 & a1 & a2 diploid workers & queens haploid drones (perhaps her brother) diploid drones a1/a2 heterozygotes: females (queens and workers) a1 or a1/a1 hemizygotes and homozygotes: males a2or a2/a2 Let’s encourage inbreeding (incest) among the honeybees: suddenly: DIPLOIDMALES! GSD by a multiple allele system --- highly “polymorphic” sex gene (many alleles)

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

19. fruit flies: honeybees: XY AA XX AA AA A male female male female haploid A potential problem with many GSD systems (including our own): 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 (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. wa/wa > (darker, more “wildtype”) wa/Df(w) o + (or wa/w-) > o wa/Y< (lighter, less “wildtype”) wa/Y; Dp(wa)/+ It must follow that: wa/Y; Dp(wa)/+ > (darker, more “wildtype”) wa/wa Recall that Muller observed X-linked gene dose effect within a sex, but not between the sexes YET: wa/wa= (same color as) wa/Y “leaky” (hypomorphic) mutant alleles twice as leaky in males vs. females Infer: wildtype allelestwice as active in males vs. females to achieve balance

22. XY XX = X-chromosome dosage compensation wildtype (normal) X-linked alleles work twice as hard in males as they do in females 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. Gynandromorph: w+/w- w- (X AA) Male (XXAA) Female w+/w- non-mosaic eye is solid red, not mosaic red and white Muller knew from gynandromorphs: white gene functioning is “cell autonomous”: a cell’s phenotype reflects its genotype with respect to the particular gene …alleles on both X’s must be active

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