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

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)

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

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

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)

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)

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" :

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)

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. 1921 2007 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

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

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

dominant masculinizer 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

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!)

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 ?

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?

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)

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

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

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

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

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

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

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