Sex chromosomes and sex determination Flashcards
Cytogenic
Cytogenetics – is the study of inheritance by visualising the structure
and function of chromosomes
Humans have 46 chromosomes (23 homologous pairs)
44 autosomes (22 pairs)
2 sex chromosomes (1 pair – XY or XX)
Chromosome structure
• Sister chromatids joined to each other at centromere • Genetic material the same between sister chromatids • Chromosomes classified based on centromere position • P = short arm (think “Petite”) • Q = long arm
Metacentric = middle submetacentric= between middle and end telocentric = the end acrocentric = close to the end
• Staining methods – G-banding
• During metaphase chromosome condense (making them visible) • This is driven by chromatin compaction • Light and dark bands on the chromosomes are revealed following Giemsa staining
•G-banding nomenclature
Bands are numbered starting from centromere
working outward
• So 1 is closer to centromere than 2
• Main bands can be divided into smaller bands
• Smaller numbers are always closer to the centromere
e.g. 3p22.1
Sex determination mode
Wide range of reproductive modes found:
- Some organisms entirely asexual
- Some alternate between short periods of sexual reproduction and long periods of
asexual reproduction.
- Most diploid organisms have only sexual reproduction
Sex determination requires
Requires sexual differentiation or phenotypic dimorphism of the two sexes.
Heteromorphic chromosomes (sex chromosomes) distinguish the two sexes.
But, genes (not just those on sex chromosomes) rather than chromosomes are the basis of sex determination.
Basis of sex determination can be genetic or nongenetic what is the difference
Genetic sex determining systems normally have populations of ½ females and ½
males.
- one sex is heterogametic, the other is homogametic (same sex chromosome morphology).
Non-genetic systems can have unequal numbers of the two sexes
Sex chromosome in insects
Many insects
Males have a single X (still called heterogametic)
Females have two X chromosomes
Males produce gametes containing EITHER X or no
sex chromosome (XO)
still heterogametic
Still diploid for all autosomes
Bird and some reptiles
Males are homogametic (ZZ)
Females are heterogametic (ZW)
Honeybees
Males are haploid
Females are diploid
Why isn’t the ratio of males to females 1:1
Secondary sex ratio (ratio at birth) – more males than females:
- Varies in different countries from ~1.06 to 1.15
Sex ratio at conception (primary sex ratio) difficult to measure / data unreliable
Why is it not 1.0?
- Do males produce more Y-bearing than X-bearing sperm?
- Are Y-bearing sperm more viable and motile?
- Is the egg surface more receptive to Y-bearing sperm?
Temperature-dependent sex determination happen in
some reptiles
How Sex determination in mammals was identified
Investigation of abnormal karyotypes led to identification of human sex determination system
Found that:
Female - X / XX / XXX
Male – XY / XYY / XXY
Y chromosome determines
male sex in humans
• In males X & Y chromosomes form a homologous pair (for meiosis)
• But only homologous in pseudoautosomal regions 1 / 2 (towards the end of the chromosmome)
• X chromosome encodes numerous genes, involved in numerous bodily processes
• Y chromosome encodes few genes – mainly associated with sperm production
Where in the Y confers male sex?
• Sex-determining Region on the Y – (SRY)
• Located close to PAR1
• Encodes a protein (testis-determining factor
or TDF)
• At ~6-8 weeks TDF causes undifferentiated
gonadal tissue to develop into testes
How was the SRY discovered?
- Crossing-over occurs within PAR
- Typically within PAR1 (because it’s larger)
- Discovered in abnormal cases where karyotype didn’t match sex phenotype
• Cross-over BELOW SRY (X chromosome containing the SRY gene = male )
• 46 XX – males (X chromosome containing the SRY gene and PAR1)
• 46 XY – females( Y chromosome containing the PAR from the X chromosome no SRY)
• But these individuals are sterile, so cannot
be transmitted
What happens if SRY is inserted into a normal XX female zygotes of mouse
• Transgenic mouse developed male sex
characteristics (remained XX
Is the same system used in Drosophila?
- Drosophila also have X and Y chromosomes
- Typically XX = female; XY = male
- Sex determined by ratio of X chromosomes to autosomes
- 1 X : 3 pairs autosomes = male
- 2 X : 3 pairs autosomes = female
Complex series of transcription factors determined by ratio of X chromosomes to autosomes
Dosage compensation
Dosage compensation refers to the equalization of most X-linked gene products between males, which have one X chromosome and a single dose of X-linked genes
• Many genes on the X chromosome perform other functions not related to sex characteristics
• There is compensation for the different gene dosages between males and females – called Lyonisation-AKA X-inactivation
How Dosage compensation is achived>
- Remember epigenetic marks are mostly deleted at fertilisation
- In females (at about 2 weeks ~ 500 cells) a random X chromosome is inactived in EACH somatic cell
- The inactivation state is maintained in all progeny from that cell
- Tissues composed of ~50% maternally inactivated & 50% paternally inactivated
Barr bodies
- Inactivated X chromosomes called Barr bodies
* But silenced X chromosome is reactivated at oogenesis
Number of Barr bodies
- Number of Barr bodies per nucleus = number of X chromosomes – 1
- XX = 1 Barr body
- XXX = 2 Barr bodies
- XXY = 1 Barr body
Human example: Red-green colour blindness - mosaicism
- X-linked recessive trait
- In males
- If recessive (mutant) allele inherited = individual colourblind
- If dominant (WT) allele inherited = individual have normal colour perception
- In females
- If homozygous dominant for wildtype allele = normal colour perception
- If homozygous recessive for mutant allele = individual colourblind
- If heterozygous = retinas are mosaics (colour perception usually good enough)
X-inactivation
what regions escape the silencing on inactive X chromosome
- Active X chromosome is euchromatic
- Silenced X chromosome is mostly heterochromatic
- Most genes are not expressed
- However some regions escape silencing on inactive X chromosome
- These regions are the PAR and the X Inactivation Centre (XIC)
- Within XIC encodes a lncRNA (Xist)
- X - Inactive specific transcript
Mechanism of X-inactivation
1. Initiation Xist gene is ONLY expressed on the silenced X chromosome (or chromosomes if XXX , etc) Xist is a long non-coding RNA Xist does not encode a protein & is not translated Xist is not transcribed on active (non-silent) X chromosome 2. Spreading Xist RNA spreads out along the silenced X chromosome(s) and coats them Xist coating attracts histone modifying enzymes inactivating the chromosome Note: Xist and PAR escape silencing 3. Maintenance Xist expression is maintained on silenced X chromosome X-inactivation can be reversed (for instance meiosis)
