Mary Lyon hypothesis: Inactivation of all but one X chromosome (dosage compensation). This allows the dosage relationship between # X and # autosomes to be the same in males and females. Females (XX) do not express a sex-linked trait more markedly than hemizygous males X Y).

Only one X chromosome required for cell to function -other X chromosomes (1 in normal individuals) are inactivated (more dense and stain darker).

Because X chromosome inactivation does not normally occur in the very early developmental stages of germ cells, each ovum still receives an X chromosome from the female parent.

Because approximately 15 % of X chromosome genes may escape inactivation, sex chromosome aneuploid individuals (ex. XXYand XXX ) can be affected by the over-expression of X chromosomegenes.

Homozygous: Ex. XAXA XaXa

Heterozygous: Ex. XAXa

Hemizygous: Having only one allele of a given gene.Ex. XAY XaY

Mosaic phenotypes in three generations of females, all heterozygous for the X-linked gene for ectodermal dysplasia. Stippling indicates areas in which sweat glands are missing. The affected areas differ in each woman because the controlling gene is inactivated randomly, even in the identical twins in generation III.

I II III

The inactivation of X chromosomes during development apparently occurs at random. Early in development, the maternally-derived X is inactivated in some cells, while thepaternally-derived X is inactivated in others. Thereafter, descendants of a particular cellhave the same X inactivated. If a female is heterozygous for an X-linked gene, she is mosaic for that trait. One of her X chromosomes is active in roughly half of her cells, while the second X is active in her other cells.

EuploidHaving a chromosome number that is an exact multiple

of the haploid number.

AneuploidHaving an abnormal number of chromosomes-usually the addition or loss of

one or two chromosomes. Not having a number that is a multiple of the haploid. Autosomal-ex. Trisomy 21 (Down’s Syndrome).

Sex Chromosomal-ex. Turner’s and Klinefelter’s Syndromes.

PolyploidHaving more that two homologous sets of chromosomes

(more that 2N; ex. 3N, 4N, etc.)

Human sex chromosome aneuploids

• 47, XXY – Klinefelter’s syndrome – One Barr body.

• 45, XO – Turner’s syndrome – No Barr bodies.

• 47, XXX – Super female – Two Barr bodies.

• 47, XYY – Super male – No Barr bodies.

Model for sex determination in mammals

• In the article “Zeroing in on the Sex Switch” that reports the work of David Page, the gene detected on the X chromosome that appeared similar to that of the SRY gene on the Y chromosome, may have been the NR0B1 gene.

• In association with the Lyon hypothesis, in which all but one X chromosome is inactivated to a Barr or chromatin body, an interplay between SRY and NR0B1 genes determines sex.

Sex-determining region Y (SRY) gene

• This has been positively identified as the gene encoding the testis-determining factor (TDF). When injected into normal (XX) female mice, it caused them to develop as males. The gene acts via two established mechanisms:

• 1) The SRY protein (TDF) binds the p450 aromatase gene and inhibits its activity. The p450 aromatase gene has a protein product that converts the male hormone testosterone to the female hormone estradiol.

• 2) The SRY protein (TDF) enhances the activity of the gene for MÜLLERIAN-INHIBITING SUBSTANCE (MIS). MIS induces testicular development and the digression of female reproductive ducts.

• Thus, the SRY protein (TDF) points an indifferent embryo toward maleness and the maintenance of testosterone production. This major sex switch initiates a developmental sequence that ultimately involves numerous genes.

PGC’S (Primordial Germ Cells; bipotential)

6 weeks (humans)

1 SRY gene (TDF) on Y chromosome and 1NR0B1 gene

(DAX1) on X chromosome.

1 NR0B1 gene (DAX1) on 1active X chromosome (XX ind.), or 1 SRY gene (TDF) on Y chromosome and 2 NR0B1genes (DAX1) on X chromosome (XY ind.)

6-16 weeks (sexualdifferentiation)

Mullerian Duct System(inc. ovaries)

Lack of male sex hormone and presence of female sex hormone from ovary stimulates development of 2º sexual organs and characteristics ( ).

Wolffian Duct System(inc. testes)

Presence of male sex hormone fromtestis stimulates development of 2º sexual organs and characteristics ( ).

Problems in sex hormone secretion in accordance with genetic sexmay cause genotypic and phenotypic sex contrast.

XX = homogametic sexXY = heterogametic sex

In some organisms [birds (chickens), moths, and some fish], the relationship between X and Y is reversed in comparison to that in mammals.

♂ (male) rather than ♀ (female) is the homogametic sex [XX (ZZ)] in these organisms.

♀ (female) rather than ♂ (male) is the heterogametic sex [XY (ZW)] in these organisms.

Gyandromorphs and Chimeras

• Gyandromorph: An individual that developed from a single fertilized egg (embryo) and which is composed of both male and female genotype cells (sexual mosaic).

• Chimera: An individual formed from two different cell lines or the fusion of two non-identical fertilized eggs (embryos), but which is composed of cells that all have the genotype of one sex (male or female).

Hermaphrodite

An individual that possesses both male and female gonads, with the social

environment usually controlling whether the individual takes on a male or female

reproductive role.

Drosophila melanogasterBilateral Gyandromorph

“Sexual Mosaic”2A2X

XW XW

Mitotic non-disjunction

Xw Xw

1 1

1 1

1 1

1 1

1 1

1) 2A 3X- metafemale

2) Red eye- XWXWXw

3) No sex comb4) Light abdomen

1) 2AX0- sterile male

2) white eye- Xw0

3) Sex comb4) Dark abdomen

1 1