Y Chromosome

1
Chapter 5

• Part 3

2
Y Chromosome

• Isnt genetically blank as once thought but very
  few genes compared to X
• Genes on Y may or may not have counterparts on X
• Both ends have pseudoautosomal regions (PARs)
  share homology with X and used as synapse area
  during meiosis
• Rest is considered non-recombining region of Y
  (NRY) but now called male-specific region (MSY)
  some is homologous to X and some unique areas
• Euchromatin area is functional genes and
  heterochromatin lacks functional genes

3
Y continued

• Between euchromatin and PAR on short arm is the
  sex-determining region (SRY) male sexual
  development gene product called
  testes-determining factor (TDF)
• gene is similar in all mammals tested
• TDF triggers embryonic gonadal tissue to become
  testis

4
Strange Sexual Devolopment

• Some males have 2X and no Y usually 1 X has an
  SRY from Y attached (broken off during
  disjunction)
• Some females have an X and Y but the Y is missing
  the SRY gene argues that SRY provides the
  primary signal for maleness
• Transgenic mice contain foreign DNA, if put Sry
  (mouse version) into XX eggs, most develop into
  males other autosomal genes help in making
  testicular tissue

5
MSY Region

• Area between the PAR divided into 3 regions
• 1) X-transposed region originally derived from
  X chromosome during human evolution, 99
  identical to Xq-21 of modern human X
• 2) X-degenerative region - 20 of MSY, more
  distantly related to X chromosomes
• 27 single copy genes and pseudogenes
  (non-functional), all share some homology with X
• 1 of the genes is the SRY gene, expressed only in
  testes but other genes are expressed in all
  tissues
• 3) Ampliconic region - 30 MSY region contains
  genes closely associated with testis formation
  no X chromosome counterparts, expression limited
  to testis
• 60 transcription units divided among 9 gene
  families, many in multiple copies
• Amplicon repeat unit, within 7 segments in
  euchromatin regions encode proteins specific to
  development and function of testes, directly
  related to fertility

6
Ratio of Males to Females

• Sex ratio actual proportion of males to females
• 2 ways to access
• primary sex ratio proportion of males to
  females conceived in a population
• secondary sex ration proportion of each sex
  that is born
• easier to determine but disadvantage of not
  accounting for any disproportionate embryonic or
  fetal mortality
• Primary sex ratio is probably close to 1 but is
  altered between conception and birth
• prenatal mortality is higher in males rather than
  females but more males are conceived to keep the
  male ratio higher

7
Suitable Explaination

• Examine assumptions on which theoretical ratio is
  based
• segregation produces equal numbers of X and Y
  bearing sperm
• each type has equivalent viability and motility
  in female genital tract
• egg surface is equally receptive to both X and Y
  sperm
• Y is smaller and speculated to be more motile
  than X sperm, may increase the number of male
  zygotes

8
Dosage Compensation

• Use to prevent over-expression of genes on the X
  chromosomes
• females have 2 X and male only 1 so they may have
  a dosage effect so can produce 2x the gene
  product
• Dosage compensation will help to keep the amount
  of gene product equal to males

9
Barr Bodies

• Dark staining body seen in the interphase in a
  nerve cell that is absent in males
• Stains with Feulgen stain that interacts with DNA
• sex chromatin body or Barr body
• helps with dosage compensation
• see multiples in females with extra X chromosomes

10
Multiple Barr Bodies

• Follow the n-1 rule where n is the number of X
  chromosomes
• If inactivated, why still abnormal inactivation
  does not normally occur in the early
  developmental stages, maybe not all of each X is
  inactivated, 15 of human X actually escape
  inactivation

11
Mom or Dad X Inactivated???

• Lyon Hypothesis inactivation of X chromosome
  occurs randomly in somatic cells at a point early
  in embryonic development and once inactivated all
  cells arising from that cell are also inactivated
• saw this in mice heterozygous for coat color
  allele is on the X chromosome
• color patches are due to the allele on one X and
  the other color because of the allele on the
  other X
• different color in adjacent patches have
  different alleles activated

12
Cat Coat Colors

• Calico and tortoiseshell (no white) cats are all
  female
• Do not see this color pattern in males as they
  have 1 X and are hemizygous for the coat color
  allele

13
Human Studies

• Used fibroblasts in cell culture and looked at
  the gene for glucose-6-PO4-dehydrogenase (G6PD)
  as it is an X-linked gene, tell mutants apart by
  protein electrophoresis
• Each female should have 2 distinct cell types and
  2 protein types
• studied 14 clones 7 had one form and the other
  7 had the other form but none had both
• Barr body formation sometimes called lyonization
  because of discoverer

14
Other Disorders Seen in Mosaic Females

• Red-green color blindness
• males who get X chromosomes are color blind but
  females may have only some cells with poor color
  perception and others with normal color
  perception
• Anhidrotic ectodermal dysplasia
• males absence of teeth, sparse hair growth and
  lack of sweat glands
• skin of heterozygous females reveal random
  patterns of tissue with/without sweat glands

15
Mechanism of Inactivation Imprinting

• Still unsure of mechanism but a memory is created
  so that the same chromosome is inactivated after
  DNA replication and cell division imprinting
• Human X has X-inactivation center (XIC) major
  control unit located on the proximal end of the p
  arm in humans only on the X chromosome that is
  inactivated
• contains 4 genes one being the X-inactive
  specific transcript XIST, critical gene, RNA is
  made but it lacks an extended open reading frame
  (ORF) so doesnt make a protein
• XIST spreads out over the X chromosome causing
  inactivation cis acting
• Xist in mice was found to be expressed from both
  X but as inactivation process continue its
  expression on the inactivated X is enhanced

16
Sex Determination in Drosophila

• Ratio of X chromosomes to sets of autosomes
• Drosophila have same general sex chromosomes as
  humans XY male, XX female but Y is not the
  determinant of maleness
• both Xs and autosomes play a role
• XXY is female and XO is sterile male
• Y lacks male determining factors but does play a
  role in fertility
• Some females have 3N number of chromosomes and
  this extra set of chromosomes wide range of
  chromosome complements is distributed to gametes
• see heavyset bodies, coarse bristles, coarse eyes
  and may be female

17
Sex Determined

• Ratio of X chromosomes to of haploid sets of
  autosomes (A)
• female normal 2X2A triploid 3X3A both
  are 11 and flies are fertile
• 3X2A or XO2A have 1.5 ratio superfemale but
  are inviable and now called metafemales
• males XY2A (normal) or XO2A (sterile) have a
  ratio of 12 or 0.5
• when decreases to 13 or 0.33 in XY3A will be
  infertile metamales
• ratio between 0.5 to 1.0 were larger, variety of
  morphological abnormalities, rudimentary bisexual
  gonads and genitalia sterile and express both
  female and male morphology intersexes
• maleness determined by autosomes and some
  femaleness is caused by genes on X, males become
  males because they lack X chromosomes
• Genic balance theory
• maleness reached at XA ratio of 12 but 2X
  (2X2A) alters balance to female

18
(No Transcript)
19
Other Mutants

• Transformer autosomal gene, tra
• female homozygous for tra become sterile malesbut
  males are inaffected as homozygotes
• Sex-lethal sxl master switch
• activation of sxl relies on ratio of 1.0 is
  essential to female development, in absence of
  activation ratio of 0.5 results in males
• mutations that inactivation sxl results in female
  embryo death but doesnt effect male embryos
• regulatory cascade requires RNA splicing remove
  some RNA and splice rest back together
• Sxl may undergo alternative splicing which means
  can get different transcripts in male and female
• transcript active in female ultimately leading to
  female differentiation
• transcript in inactive in males, leads to
  different gene activity whereby male
  differentiation occurs

20
Temperature Variation

• Sex determination in some reptiles is influenced
  by temperature
• Many species of reptiles, sex is determined at
  conception by chromosome composition
• Many snakes are ZZ (male) or ZW (female), boas
  and pythons cant tell sex chromosomes apart
• Lizards are either XX/XY or ZZ/ZW depending on
  species

21
Crocodiles, Most Turtles and Some Lizards

• Due to incubation temperature of eggs
• 3 distinct patterns
• low temps 100 female high temps 100 male
• opposite of above
• low and high temps 100 female intermediate
  temp 100 male

22
2 Noteworthy Observations

• 1) Under certain temperature in all 3 patterns
  both male and female offspring results
• 2) Pivitol temperature (Tp) is usually lt5?C and
  may only be 1?C
• How does temperature influence sex?
• thought to involve steroids mainly estrogen and
  enzymes involved in synthesis
• aromatase converts androgens to estrogens
• aromatase genes transcription may be
  thermosensitive
• Hormones may play role in birds, fish and
  amphibians as well