Sex Determination and Sex Linkage

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Sex Determination and Sex Linkage From The
Cartoon Guide to Genetics Gonick and
Wheelis Harper Perennial Ed.
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Fly Lab, Columbia U, 1910s
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Law of Segregation at work
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• A wild type fruit fly heterozygous at the w locus
  is mated to a
• wild type male. What is the ratio of wild type
  (red eye) to white eye flies
• of any sex?
• Answers
• 3 wild type 1 white eye
• 1 wild type 1 white eye
• 3 white eye 1 wild type
• All wild type

a. Is the correct answer
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A wild type fruit fly heterozygous at the w locus
is mated to a wild type male. What is the ratio
of wild type males to white eye males?
Answers a. 3 wild type 1 white eye b. 1 wild
type 1 white eye c. 3 white eye 1 wild type d.
All wild type
b. Is the correct answer
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Homogametic heterogametic
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Only 2 major regulatorygenes TDF and AR
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TDF(testes determining factor) AR (androgen
receptor)
TDF(Sry)
Pseudoautosomal regions
Y
X
AR
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How do this system work?
Males

• The TDF gene is activated in 6-week old XY
  embryos for only 48 hrs
• This activity turns on a set of genes allowing
  testes to develop
• Testosterone is produced and received by receptor
  produced by AR gene.
• This triggers program for male genitals to
  develop

How do we know? TDF-transgenic female embryos in
mice are males
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Females

• In the absence of TDF, a different set of genes
  is turned on resulting in the synthesis of female
  hormones.
• These will program development of female genitals

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Accidents in nature
What happens when TDF is translocated to the X
chromosome
We get a XX-TDF male, but sterile, 2 X
chromosomes in the male germline kill sperm cells
What happens when AR is defective and no receptor
is produced?
We get a XY female with internal testes, but
phenotipically female and sterile (lack of 2 Xs
lethal in female germline). Same result when TDF
is missing in Y chromosome
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Recent Findings on the Y chromosome

• Y chromosome is 1/50 of the total genome
• Y contains approximately 78 protein-coding genes
• (versus gt1200 genes on X-chromosome)
• X-Y chromosomes relatively recent inventions,
  originated in mammals 300 mya from autosomes
• TDF (Sry) might originate from Sox3 on X
• Due to lack of recombination, Y is in constant
  decay, predicted to be gone in 10 million years!

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Males, the weaker sex
During fertilization, there seems to be excess of
male embryos Y sperm swims faster than
X-sperm? After that, everything goes
downhill Before birth males cope less well than
females eg. Less twin boys than girls Boys
suffer more brain damage and birth defects eg.
color blindness, muscular dystrophy By age 80,
only 1/3 of population is male
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Dosage compensation by X chromosome inactivation
Barr body
XX
XXX
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Interesting observations related to X-chromosome
inactivation

• Mammalian females are X chromosome mosaics.
• Most genes inactivated, but not all.
• Identical twin girls are less similar than
  identical twin boys, because of X chromosome
  inactivation (Discordant) twins.
• Autoimmune disease more frequent in females than
  males, because immune system could attack cell
  using a different X chromosome.