1

SEX DETERMINATION

• The mechanisms for sex determination are genotypic sex determination systems, in which sex is governed by the genotype of the zygote and environmental sex determination systems in which sex is governed by internal and external environmental conditions.

• In genotypic sex determination the sex chromosomes play a decisive role in the inheritance and determination of sex.

2

• In humans and other placental mammals the mode of sex determination is the Y-chromosome mechanism. The Y chromosome of the heterogametic sex is active in determining the sex of an individual.

• Individuals carrying the Y chromosome are genetically male, while individuals lacking the Y chromosome are genetically female.

• Since the Y chromosome determines maleness in placental mammals it must uniquely carry an important gene that encodes a product that sets the switch toward male sexual differentiation.

• This product is called testis-determining factor. The testis-determining factor causes the gonadal primordia to differentiate into testes instead of ovaries.

3

• This is the central event in sex determination of mammals, all other differences are secondary effects resulting from hormone action.

• The male producing effect of the Y chromosome is due to a gene called SRY (sex- determining region of the Y chromosome) in humans and Sry in mice.

• In the absence of SRY, a related gene enables the undifferentiated gonad to develop into ovaries instead of testes.

• In fish the gene for sex determination has been named DMY. It is expressed exclusively in XY embryos but not in XX embryos. DMY plays a pivotal role in testicular differentiation and sex determination in fish.

4

• The sex chromosomes are designated as the X chromosome and the Y chromosome. In humans and many other animals the female has two X chromosome (she is XX) while the male has one X chromosome and one Y chromosome (he is XY).

• The male produces two kinds of gametes (X or Y bearing gametes ) and is called the heterogametic sex. The female produces only one type of gamete (X bearing gametes) and is called the homogametic sex.

5

• Random fusion of these gametes produces an F1 generation with ½XX (females) and ½XY (males) .

• Thus, the X and Y chromosomes carry genes that determine the sex of an individual

`

6

P generation parent 1 x parent 2 Parental phenotype Female Male Parental genotype XX XY Gametes all X ½ X, ½ Y F1 generation F1 genotype ½ XX, ½ XY F1 phynotype ½ females ½ males

Interbreeding F1 generation parent 1 x parent 2 F1 phenotype Female Male F1 genotype XX XY F1 Gametes all X ½ X, ½ Y F2 generation F2 genotype ½ XX, ½ XY F2 phynotype ½ females ½ males

7

• XX – normal female• XY – normal male• XO – female and sterile (turner syndrome)• XXX –mostly normal females, although are

slightly less fertile.• XXY – male with Klinefelter syndrome (have

undeveloped testes, taller than normal and some degree of breast development).

• XXXY- Klinefelter syndrome • XXYY - Klinefelter syndrome • All these defects indicate that two X chromosomes

are needed for normal development in females and one X and one Y chromosome are needed for normal development in males. Mammals can tolerate abnormalities in the complement of sex chromosomes but very rare for autosomes

8

X chromosome-autosome balance system

• In Drosophila and the nematode, Caenorhabditis elegans, the main factor in sex determination is the ratio between the number of X chromosomes and the number of sets of autosomes.

• In Drosophila the homogametic sex is the female (XX) and the heterogametic sex is the male (XY).

• Drosophila melanogaster has four pairs of chromosomes, one pair of sex chromosomes and three pairs of autosomes. Since it is a diploid, there are two sets of autosomes in a wild-type fly.

• In normal female there are two X chromosomes and two sets of autosomes (A), hence the X:A ratio is 1.

•

9

• A normal male has one X chromosome and two sets of autosomes (A), hence the X:A ratio is 0.5.

• If the X:A ratio is greater than or equal to 1.00, the fly will be female. If the X:A ratio is less than or equal to 0.50 the fly will be male. If the ratio is between 0.50 and 1.00 the fly is neither male nor female it is an intersex.

10

Sex linkage

• Sex linkage is the physical association of genes with the sex chromosomes of eukaryotes.

• A particularly important category of genetic linkage has to do with the X and Y sex chromosomes.  These not only carry the genes that determine male and female traits but also those for some other characteristics as well. 

• Genes that are carried by either sex chromosome are said to be sex linked.

11

• Sex linkage was discovered by Thomas Morgan in 1910 when using fruit fly (Drosophila) in genetic experiments.

• Morgan crossed white-eyed male with a red-eyed female. All the F1 were red-eyed. So, the white-eyed trait was recessive to the red-eyed trait.

• He allowed the F1 progeny to interbreed, and in the F2 generation there were 3,470 red-eyed and 782 white-eyed flies. These numbers didn’t fit the Mendelian 3:1 ratio. Also all the white-eyed flies were males.

12

• Morgan did a reciprocal cross by crossing a white-eyed female with a red-eyed male. All the the F1 females were red-eyed and all the F1 males have white eyes.

• Interbreeding of the F1 (white eyed-males and red-eyed females) gave equal number of males and females with red and white eyes in the F2.

• The results were different from those obtained in the first cross in which none of the females and half of the males exhibited the white-eyed phenotype.

• Morgan proposed that the gene for the eye colour is located on the X chromosome. The difference in the phenotypic ratios in the two crosses reflects the transmission pattern of sex chromosomes and the gene they contain.

13

• The females receive one X chromosome from their father and one X chromosome from their mother. The males receive their only X chromosome from their mother.

• The condition of X-linked genes in males is said to be hemizygous since the gene is represented only one time because there is no corresponding allele on the Y chromosome.

• Morgan postulated that the alleles for red or white eye colour are present on the X chromosome but there is no counterpart allele of this gene on the Y chromosome. Thus, females would have two alleles for this gene whereas males would have only one.

14

• The genetic results were consistent with the meiotic behaviour of the X and Y chromosomes.

• The special inheritance of the eye colour genes makes it likely that they are borne on the X chromosome. This strongly supports the notion that genes are located on hromosomes.

• Genes that are located on the X chromosome are referred to as sex-linked or more correctly X-linked because the gene locus is part of the X chromosome.

15

The inheritance of X-linked genes

P generation parent 1 x parent 2 Parental phenotype Female, red -eyes Male, white eyes Parental genotype Xw+ Xw+ Xw Y Gametes all Xw+ ½ Xw , ½ Y F1 generation F1 genotype ½ Xw+

Xw , ½ Xw+ Y

F1 phenotype ½ female, red eyes ½ male, red eyes

Interbreeding F1 generation parent 1 x parent 2 F1 phenotype Female, red eyes Male, red eyes F1 genotype Xw+

Xw Xw+ Y F1 Gametes ½ Xw+

, ½ Xw ½ Xw+ , ½ Y

16

F2 generation Male gametes Female gametes ½ Xw+ ½ Y

½ Xw+ ¼ Xw+Xw+ ¼ Xw+

Y

½ Xw ¼ Xw+ Xw ¼ XwY

F2 genotype ¼ Xw+Xw+, ¼ Xw+

Xw, ¼ Xw+ Y, ¼ XwY

F2 phynotype: all females are red eyes,

½ males are red eyes and ½ males are white eyes

(F1 x F1)

17

Reciprocal cross

P generation parent 1 x parent 2 Parental phenotype Female white- eyed Male red-eyed Parental genotype XwXw Xw+Y Gametes all Xw ½ Xw+, ½ Y F1 generation F1 genotype ½ Xw+

Xw, ½ Xw Y

F1 phenotype ½ female red-eyed ½ male white-eyed

Interbreeding F1 generation parent 1 x parent 2 F1 phenotype Female red-eyed Male white-eyed F1 genotype Xw+

Xw Xw Y F1 Gametes ½ Xw+

, ½ Xw ½ Xw , ½ Y

18

F2 generation Male gametes Female gametes ½ Xw ½ Y

½ Xw+ ¼ Xw+Xw ¼ Xw+

Y

½ Xw ¼ Xw Xw ¼ XwY

F2 genotype ¼ Xw+Xw, ¼ Xw

Xw, ¼ Xw+ Y, ¼ XwY

F2 phynotype: ½ female red-eyed and ½ female white-eyed

½ male red-eyed and ½ male white-eyed

(F1 x F1)

19

Sex determination in birds

• In birds (also in butterflies, moths and some fish) the sex chromosome composition is the opposite of that in mammals: the male is homogametic sex and the female is heterogametic sex.

• Sex chromosomes are designated as Z and W. The males are ZZ and the females are ZW.

• Genes on the Z chromosome behave just like X-linked genes in mammals, except that hemizygosity is found in females (see the example of inheritance of barred plumage in poultry).

20

Sex-linked inheritance in chickens

P generation female parent x male parent Parental phenotype barred plumage nonbarred plumage Parental genotype ZBW ZbZb Gametes ½ ZB, ½ W all Zb F1 generation F1 genotype ½ ZBZb, ½ ZbW F1 phenotype ½ barred males ½ nonbarred females Interbreeding of F1 (F1 x F1) F1 generation female parent x male parent F1 phenotype nonbarred plumage barred plumage F1 genotype ZbW ZBZb F1 Gametes ½ Zb, ½ W ½ ZB, ½ Zb

21

F2 generation

Male gametes Female gametes

½ ZB ½ Zb

½ Zb ¼ ZBZb ¼ ZbZb

½ W ¼ ZBW ¼ ZbW

F2 genotypes ¼ ZBZb, ¼ ZBW, ¼ ZbZb, ¼ ZbW F2 phenotypes ½ barred ½ nonbarred (½ females, ½ males) (½ females, ½ males)

(F1 x F1)

22

Inheritance of X-linked recessive genes

• A trait due to a recessive mutant allele carried on the x chromosome is called an X-linked recessive trait.

• In X-linked recessive traits the female must be homozygous for the recessive allele in order to express the mutant trait. The trait is expressed in the male who possesses one copy of the mutant allele on the X chromosome.

• Affected males normally transmit the mutant gene to all their daughters but to none of their sons.

• All sons of a homozygous mutant mother should show the trait, since males receive their only X chromosome from their mothers.

23

• The sons of heterozygous (carrier) mothers should show an approximately 1:1 ratio of normal individuals to affected individuals.

• From a mating of a carrier female with a normal male all daughters will be normal and half the sons will express the trait.

• A male expressing the trait, when mated with a homozygous normal female will produce all normal children, but all the female progeny will be carriers.

• The X-linked dominant traits follow the same pattern of inheritance as the X-linked recessives, except that heterozygous females express the trait.

24

Nondisjunction of X chromosome

• Morgan’s work showed that from a cross of a white-eyed female (XwXw) with a red-eyed male (Xw+Y), all the F1 males should be white-eyed and all females should be red- eyed.

• Calvin Bridges found that there are rare exceptions to this result, he found about 1 in 2000 of the F1 flies were either white-eyed females or red-eyed males.

• Bridges hypothesized that a problem had occurred with chromosomes segregation in meiosis in the female, the paired X chromosomes failed to separate, so eggs were produced with either two X chromosomes or no X chromosomes .

25

• The failure to separate of the homologous chromosomes is called nondisjunction. Nondisjunction of the X chromosomes can explain the exceptional flies.

• When the eggs were fertilized by the two types of sperm (Xw+-bearing and Y-bearing), the result was four types of zygotes: XXX and YO zygotes which died before development was completed. The surviving were XO zygotes which were red-eyed males and XXY zygotes which were white-eyed females.

• Bridges examined microscopically the chromosomes of the exceptional progeny and indeed they were of the type he had predicted i.e. XXY and XO.

26

Primary nondisjunction

P generation female parent x male parent Parental phenotype white eyes red eyes Parental genotype XwXw Xw+Y Nondisjunction in female Normal meiosis in male Gametes ½ XwXw, ½ O ½ Xw+ , ½ Y F1 generation F1 genotype ¼ Xw+XwXw, ¼ YO, ¼ XwXwY, ¼ Xw+O F1 phenotype ½ die in early ¼ white-eyed ¼ red-eyed

development females males(sterile)

27

Secondary nondisjunction

P generation female parent x male parent Parental phenotype white eyes red eyes Parental genotype XwXwY Xw+Y Secondary nondisjunction in female Normal meiosis in male Gametes ½ XwXw, ½ Y ½ Xw+ , ½ Y F1 generation F1 genotype ¼ Xw+XwXw, ¼ YY, ¼ XwXwY, ¼ Xw+Y F1 phenotype ½ die in early ¼ white-eyed ¼ red-eyed

development females males