Autosomes versus Sex Chromosomes

Autosomes versus Sex Chromosomes • In some organisms, there are 1 or 2 specialized chromosomes • sex chromosomes • involved in sex determination • X and Y or Z and W • Autosomes - all the others!

Sex Linkage • In organisms with X and Y chromosomes, the Y carries no genes absolutely necessary for survival • The X chromosome is necessary for survival • Analogous for ZZ, ZW

Sex Linkage • Females and males differ in possible genotypes for X - linked loci • Females may be heterozygous or homozygous • AA, Aa, aa • Males are hemizygous • A , a

Sex Linkage • For sex-linked (or X-linked) traits, a male’s genotype is known by his phenotype! • Males have the trait or don’t • No chance for heterozygous males

Sex Linkage and Reciprocal Crosses • Sex linkage is often identified by the results of reciprocal crosses • Reciprocal crosses yield identical results with autosomal loci • AA x aa --> Aa • Reciprocal crosses give very different results w/ sex-linkage! • AA x a versus aa x A

aa x A Sex Linkage and Reciprocal Crosses a AA x a A A a

Aa x A Aa x a Sex Linkage and Reciprocal Crosses F2 results: A A a a A a

red female x white male RR r White eyes in Drosophila white female x red male rr R r R R r

Rr x R Rr x r White eyes in Drosophila F2 results: R R r r R r

Sex Linkage in Humans • Hemophilia • lack of blood clotting factor • blood does not clot properly • simple cut or bruise can lead to uncontrollable bleeding • fatal until recently

Hemophilia • Females • HH normal, non-carrier • Hh normal, carrier • hh hemophiliac • Males • H normal • h hemophiliac

Hh X H H H h HH H Hh h Hemophilia The disease is usually passed from a carrier mother to a son

Hh x h Hemophilia For a female to have hemophilia, she must have a carrier mother and a hemophiliac father h H h

Patterns of sex linked inheritance • traits appear to “skip” generations • passed from carrier mother to 1/2 sons • 1/2 daughters expected to be carriers also • trait cannot be passed from father to son • all daughters of a father with the trait will be carriers

Patterns of sex linked inheritance • Crosses producing males of one phenotype and females of another are a strong indication of sex linkage • The NUMBERS of each sex are not affected! The sex ratio remains the same.

Humans, mammals, many others: XX = female XY = male Lepidopterans, most birds, some others: ZZ = male ZW = female Heterogamy • Homogametic sex: 2 like chromosomes Heterogametic sex: 2 unlike chromosomes

Sex Determination in Drosophila Gender is determined by the ratio of X’s to the sets of autosomes - “Genic Balance” Normal female: 2 X’s, 2 sets of autosomes; X : A = 1.0 Normal male: 1 X, 2 sets of autosomes: X : A = 0.5 X : A > 1.00 ----> “metafemale,” sterile, reduced viability X : A ~ 0.67 ----> intersex X : A < 0.50 ----> “metamale,” sterile, reduced viability

Sex Determination in Drosophila • Sex determination also affected by heat and cold shock • Several genes impact on sex determination • Doublesex; produces intersexes • Transformer; females converted to sterile males • Sex ratio genes; alter 1:1 sex ratio

Sex Determination in Humans • Simplest terms: presence of Y = male absence of Y = female • ONE GENE on the Y needed for development of testes from rudimentary embryonic gonadal tissue • testosterone from testes causes “cascade” in development of genitalia, etc. • many minor genes involved

Just what is the “male” gene? SRY = sex-determining region of the Y (Tdf) Master regulatory gene for sex determination SRY ZFY ZFY needed for sperm production

Dosage Compensation and X Inactivation • Dosage Compensation • Females do not have twice the number of active X linked genes as males • Mechanism exists so that only one X functions in females • Barr bodies

Dosage Compensation and X Inactivation • In any individual w/ more than 1 X, the extra(s) condense into a Barr body • dark spot on nuclear envelope • inactivated X chromosome • When does inactivation occur? Is the Barr body completely inactive? • active at some time, at least partially

Dosage Compensation and X Inactivation • XO - Turner Syndrome • female • no Barr body • XXX - female • two Barr bodies • XXY - Klinefelter Syndrome • male • one Barr body

Dosage Compensation and X Inactivation • Lyon Hypothesis • Which X inactivates is initially a random event • Early in embryonic development, one X shuts down; cannot reactivate • All descendents of that cell have same X inactivated

Dosage Compensation and X Inactivation • Considering one locus; homozygotes have identical cells: AA AA AA AA AA AA

Dosage Compensation and X Inactivation • Heterozygotes are mosaics of phenotypes Aa Aa Aa Aa Aa Aa Aa Aa Aa Aa Aa Aa Aa

Dosage Compensation and X Inactivation • Some mosaics are visible • Ectodermal dysplasia • Absence of sweat glands (absence of some teeth, early baldness) • Heterozygotes show patches of skin w/ sweat glands, patches w/o sweat glands

Mosaicism • Hemophilia • Heterozygous females have half the amount of clotting factor as homozygous dominants • Lesch-Nyhan Syndrome • Carrier females show some symptoms from not having a full complement of gene product

Mosaicism • Tortoiseshell/Calico cats • sex linked gene • B = black; b = yellow • Possible genotypes:males: B7b7females: BB Bbbb

Heterozygous females: Bb Bb Bb Bb Bb Bb Bb Bb Bb Bb Bb Bb Bb Bb Bb Bb

Meow.

Autosomes versus Sex Chromosomes