The Kangaroo Genome Project

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Selfish genes and sex Jenny Graves, ANU, Canberra
Battle of the sexes
Genes on X and Y
Origin of X and Y
Fate of the Y
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JennyTech Labs, 2001
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Human sex chromosomes Female Male
XX X
Y
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Genome wars Female Male
XX X
Y
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Battle of the sexes different strategies
Few gametes Parental care
Many gametes No parental care
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Human sex chromosomes
X X X Y
SRY
1340 widely expressed
45 most testis-specific
female male
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Which is the testis determining gene?
Jamie Foster, Andrew Sinclair
ZFY is the wrong gene
SRY is the right gene
SOX3 ancestor of SRY
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Human sex chromosomes
Problems at meiosis Dosage problems
Sex-linked diseases Sex-reversal syndromes
SRY
X Y
Why so weird? so they work optimally?
evolutionary accident?
XXXXXXXXXXXXXXXXX
Dumb design!
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XY evolution

Once the X and Y were an ordinary pair
proto-XY
One partner acquires a male-determining gene
Other male-advantage genes accumulate -
recombination suppressed
Y degraded by deletion, mutation
And degraded and degraded
And could even disappear
The Y is a degraded X
X Y
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The conservative X
shared by all placental mammals lots of
genes many different functions
X Y
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X chromosome genes
Immaculate Controlling Smart Sexy
X X X X
brains-and-balls genes
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Why do X genes acquire male roles?
Recessive super-sperm mutant on autosome on
X
F M
F M
S
S
S
S
A A A A
X X X Y
Sexually antagonistic genes
Big brain mutant??
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Brains and balls hypothesiswhy so many X-linked
syndromes with mental retardation and gonad
abnormalities?
Sexual selection for intelligence
Multifunctional protein
Selection for male reproduction
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The weird Y
Mostly junk Few genes, most shared with X
Genes have male-specific functions Different
animals have different sets of Y genes
X Y
Why? so it works better? evolutionary
accident?
XXXXXXXXXXXXXXX
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Genes on Y are relics of genes on X
Most Y genes have copies on X
SRY Sex determination
RBMY Spermatogenesis
TSPY Spermatogenesis?
Y
Widely expressed Testis
expressed
Brains-and-balls genes
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How did Y genes evolve from X genes?
HMG box
SOX3
CNS, testis
Testis determination Human SRY Mouse SRY Kangaroo
SRY
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Why did Y genes acquire male roles?
Recessive super-sperm mutant on autosome
on Y
F M
F M
S
S
S
S
A A A A
X X X Y
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Progressive loss of sex genes from Y

• X Y

SOX3 ZFX UBE1X SMCX ATRX RBMX RPS4X
SRY ZFY UBE1Y SMCY ATRY RBMY RPS4Y
SRY ZFY UBE1Y SMCY ATRY RBMY RPS4Y
SRY ZFY SMCY RBMY
Is the Y doomed to disappear?
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Y chromosome models
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Why does the Y degrade?
High variation frequent mutation, deletion,
insertion
Inefficient selection/Drift no recombination
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Origin of mammal XY pair
Placental mammals
Mammals
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Vertebrate sex chromosomes
Monotremes Marsupials Placentals
?
XY
Reptiles and birds
Amphibians
148
166
Mammals
Fish
310
Amniotes
410
Tetrapods
450
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Marsupial sex chromosomes XX female XY male
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Kangaroo male 7 chromosome pairs small X,
tiny Y
1 2 3 4
5 6 7 X Y
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Building blocks of the human X and Y
human X genes in kangaroo
chr 5
Added Ancient
chr X
Human X
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A
4 genes
41 genes
7 genes
Y
Y
X
X
Marsupial Human
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Vertebrate sex chromosomes
Monotremes Marsupials Placentals
Reptiles and birds
XY
?
XY
Amphibians
148
166
Mammals
Fish
310
Amniotes
410
Tetrapods
450
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Bird sex chromosomes
Male ZZ
Female ZW
Chicken ZW parts of human 9,5 Mammal XY parts
of bird 4,1
Dosage of Z-linked DMRT1 determines sex
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Is the bird ZW conserved?
Emu ratite bird, 80MY
Sex chromosomes ZW
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1q
A
A
Y
X
X
4
Chicken Marsupial Human
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Marine turtles TSD
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Evolution of sex chromosomes

dragons turtles alligators
frogs many fish
humans mice
kangaroos
X Y W Z
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Vertebrate sex chromosomes
Reptiles and birds
Monotremes Marsupials Placentals
?
TSD XY ZW
XY
XY
Amphibians
148
ZW
166
Mammals
Fish
310
Amniotes
410
Tetrapods
450
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Platypus sex chromosomes?
? ? ? ? ? ? ? ? ? ?
X1 Y1 X2 Y2 X3 Y3
X4 Y4 X5 Y5
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The New York Times, December 2004
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Platypus sex chromosomes at meiosis
Y5
Telomeric marker
5X 5Y
X5
Y4
X4
Y3
X3
Y2
X2
Y1
X1
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Famous scientists explain examples of apparently
dumb design in nature
Famous scientists explain examples of apparently
dumb design in nature
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1q
A
A
Warren et al et al et al Nature 2008
Y
6
X
X
4
Chicken Platypus Marsupial Human
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Genes on platypus sex chromosomes
No homology to human X
Homology to chicken Z
Veyrunes, Waters Gen. Res. 2008
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Vertebrate sex chromosomes
Reptiles and birds
Monotremes Marsupials Placentals
TSD,XY,ZW XY ZW
XY
XY
XYXYXYXYXY
Amphibians
SRY
148
ZW
166
ZW
Mammals
Fish
310
ZW
Amniotes
410
Tetrapods
450
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Evolution of vertebrate sex determination
TSD reptile
Birds
Platypus
Kangaroo
Human
9
ZW
X Y X Y X Y X Y X Y
5
DMRT1
DMRT1
DMRT1
DMRT1
DMRT1
1
1
5
X Y
X Y
6
4
4
SRY
SOX3
SOX3
SRY
SOX3
SOX3
SOX3
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The future of sex

• When will our Y disappear?
• 166 MYA the Y had 1340 genes
• Today the Y has 45
• Genes lost per MY 1300/166 7.8

At this rate Y will disappear in 5.8 MY
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Will males disappear?
Parthenogenic females?
XXXXXXXXXXXXXXXX
New sex determining genes?
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Hope for the future of men .
Mole voles - males have no Y, no SRY
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New hominid species?

• What if
• mole vole XX
• man woman

1 male 1 female 2 intersexes Infertility gt
species divergence??
Graves 2006, Cell
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Graves lab Sex and Y team Andrew Sinclair Jamie
Foster Francine Brennan Patrick Western Rob
Glas Swathi Shetty Andrew Pask Roland
Toder Rachael ONeill Margaret Delbridge Paul
Waters Frank Grützner Mary Wallis Tariq
Ezaz Veronica Murtagh Denis OMeally
Collaborators Steve Sarre, Arthur Georges Univ.
Canberra Ikuo Miura Univ. Hiroshima Marilyn
Renfree Univ. Melbourne Malcolm Ferguson-Smith
Cambridge Scott Edwards Harvard
Friendly Genome Centres Wash U Wes
Warren JGI Jeff Boore, Gerry Rubin Sanger Mark
Ross RIKEN/NIG Asao Fujiyama
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Gene loci on the human X and Y
SNF addiction to sentimental movies NAG
repetitive requests to tidy up BTT I8U
mate choice locus U2 TTTT playful but
irritating mating behaviour ICU X-ray vision to
detect clandestine mating behaviour YAX
tendency to long phone conversations MT
inability to fill gas tank of car ITS9 inability
to set electronic alarm clock EH? response to
smutty jokes BOT husbands credit card control
locus RT pretensions to cultural
activities MAC8 susceptibility to eating
disorders PMT cyclical mood
variation BCH-E ZZZ response to exciting
televised cricket necessity to reorient
directions when driving south PNP SNS Jane
Austen appreciation locus MR
p22 p21 p11 q11 q12 q13 q21 q22 q23 q24
q25 q26 Q27 q28
MAP