sexy x wimpy y jenny graves la trobe, ucanberra, anu beginnings of our xy sex chromosomes are weird...
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Sexy X
Wimpy Y
Jenny GravesLa Trobe, UCanberra, ANU
Beginnings of our XY
Sex chromosomes are weird
The disappearing Y
Weird animal genomes, sex and
the future of men
Human XY and sex
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JennyTech Labs, La Trobe 2001
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testicles
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Human sex and sex chromosomes
female male
X X X YTDF
testis
hormones
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Where is TDF?Female Male
XX X Y
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TDF IS ON THE Y CHROMOSOME
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Zooming in on TDF
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Zooming in on TDF
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SRY is the right geneSOX3 ancestor of SRY
Discovery of the testis determining gene
ZFY is the wrong gene!
Jamie Foster, Andrew Sinclair
SOX9 target of SRY
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X and Y chromosomes are weird
X1669 genes
Many different functionsMany sex, intelligence genes
Brains-and-balls genes
YOnly 27 genes specific to YMany copies, pseudogenesMale-specific functions Sex and spermatogenesis
PARShared by X and YContains 24 genes
Smart,Sexy X
Wimpy Y
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• Problems at meiosis• Dosage problems• Sex-linked diseases• Sex-reversal syndromes
Why so weird? • so they work optimally?• evolutionary accident?
XXXXXXXXXXXXXXXXX
X Y
Dumb design!
Sex chromosomes are trouble
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X Y
proto-XY
XY evolutionOnce the X and Y were an autosome pair
One partner acquires a male-determining gene
Nearby genes acquire male-advantage functions- recombination suppressed
Y degraded by deletion, mutation
And degraded and degraded
And could even disappear
The Y is a degraded X
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MAMMALS
Fish450
TETRAPODS
Amphibians
410
Monotremes
166
AMNIOTES
Birds andReptiles
310
Placentalmammals
Marsupials
148
Beginnings of our XY
Humanmice
milli
on ye
ars
105
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Mammals
Amniotes
Tetrapods
Fish
Amphibians
Reptiles and birds Monotremes Marsupials Placentals
450
410
310
166148
XY
Origin of human sex chromosomes
HumanMouse
105
X
Elephant
Map human X genes/DNA in other species
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Sex chromosomes in weird animals
kangaroos are XX female, XY male
1 2 3 4 5 6 7 X Y
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Map kangaroo homologuesof human X genes
e.g. XPCT PGK
X
X
Is it the same XY?Paint kangaroo X DNA
onto human chromosomes
Human Xq = kangaroo X
..
ZFX
..5
5
Human Xp = kangaroo 5
Mostly
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Y
X
Origin of human XY
Elephant
XX
A
Kangaroo Human
Map orthologues of human X genes
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Y
Chicken Platypus Kangaroo Elephant Human
X64
1qA
X
A
X
Origin of human XY
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Platypus sex chromosomes
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Platypus sex chromosomes?Female: 26 pairsFemale: 26 pairs
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Platypus sex chromosomes?
X1 Y1 X2 Y2 X3 Y3 X4 Y4 X5 Y5? ? ? ? ? ? ? ? ? ?
Female: 26 pairsMale: 21 pairs + 10
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The New York Times, December 2004
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X1
X2
X3
X4
X5
Y5
Y4Y3
Y2
Y1
Platypus sex chromosomes at meiosis
5X+5Y
Telomere sequences mark chromosome ends Grutzner et al, Nature 2004
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Genes on platypus sex chromosomesNo homology to human X
Platypus genome projectVeyrunes, Waters Gen. Res. 2008
Homology to chicken Z DMRT1
AMH
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Y
Chicken Platypus Kangaroo Elephant Human
X64
1qA
X
A
X
Origin of human XY
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Male FemaleZ Z Z W
Bird sex
W is a degraded ZChicken
Emu
No SRYSex gene is DMRT1
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Temperature Sex Determination - TSDe.g. Crocodiles and marine turtles
Bird ZW = a turtle autosome
Chick Z paint
6
6
Epigenetic sex
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MAMMALS
AMNIOTES
TETRAPODS
Fish
Amphibians
Reptiles and birds Monotremes Marsupials Placentals
450
410
310
166148
XYXYA
Age of human sex chromosomes
MY
SRY
SRY is 148-166 million years old
AASOX3 SOX3 SOX3 SOX3 SOX3 SRYSRY
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166 million years ago – the Y had 1669 genes
Today – the Y has 45 genes
Genes lost per MY = ~1624/166 = ~9.8
At this rate Y will disappear in 4.6 MY
END OF THE Y
WHEN?
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Will males disappear?
New sex determining genes?
Parthenogenic females?XXXXXXXXXXXXXXXX
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Hope for men !
Amami-Osima Island
Tokunoshima Island
Okinawa-jima Island
Tokunoshima spiny rat (T. tokunoshimensis)
Amami spiny rat (T. osimensis)
Okinawa spiny rat (T. muenninki )
female male XO XO
no SRY
Koroiwa et al, 2010
SRY
female male XX XY
no SRY
female male XO XO
Japanese spiny rats have survived loss of Y
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What if XX spiny rat woman man
War of the sex genes
Infertility
–> species divergence
New hominid species?
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Team Platypus: Frank Grutzner, Pat Miethke, Paul Waters, Daniel Macmillan Janine Deakin, Ke Jun Wei
SnakesDenis O’MeallyYoichi MatsudaTeam Dragon Arthur Georges,
Alex Qinn,Tariq Ezaz, Janine Deakin, Kazumi Matsubara, Claire Hollely Frogs Ikuo Miura
Nis El-Moghabel
EmuSwathi Shetty
ARC
ARC
ARC
ARC
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Genes on the human sex chromosomes
p22
p21
p11
q11q12q13
q21
q22
q23q24q25
q26
Q27
q28
SNF addiction to sentimental moviesNAG repetitive requests to tidy upBTT I8U mate choice locusU2
TTTT playful but irritating mating behaviourICU X-ray vision to detect clandestine
mating behaviourYAX tendency to long phone conversations
MT inability to fill gas tank of carITS9 inability to set electronic alarm clock
EH? response to smutty jokes
BOT husband’s credit card control locusRT pretensions to cultural activities
MAC8 susceptibility to eating disorders
PMT cyclical mood variationBCH-EZZZ response to exciting televised cricket
necessity to reorient directionswhen driving south
PNPSNS Jane Austen appreciation locusMR
MAP
X Y
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Don’t laugh at weird animals
THE FAR SIDE Garry Larsen
MORAL
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Graves lab Sex and Y teamAndrew SinclairJamie FosterFrancine BrennanPatrick WesternRob GlasSwathi ShettyAndrew PaskRoland ToderRachael O’NeillMargaret DelbridgePaul WatersJanine DeakinFrank GrütznerFred VeyrunesMary WallisTariq EzazVeronica MurtaghDenis O’MeallyClaudia Rodriguez Delgano
CollaboratorsMarilyn Renfree Univ. MelbourneFujiyama, Matsuda, Miura NIG, Nagoya, HiroshimaMalcolm Ferguson-Smith CambridgeArthur Georges, Steve Sarre Univ. Canberra
Friendly Genome CentresWash U `Wes WarrenJGI Jeff Boore, Gerry RubinSanger Mark RossUConn Rachel O’Neill, Andy Pask