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

JennyTech Labs, La Trobe 2001

testicles

Human sex and sex chromosomes

female male

X X X YTDF

testis

hormones

Where is TDF?Female Male

XX X Y

TDF IS ON THE Y CHROMOSOME

Zooming in on TDF

Zooming in on TDF

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

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

• 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

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

MAMMALS

Fish450

TETRAPODS

Amphibians

410

Monotremes

166

AMNIOTES

Birds andReptiles

310

Placentalmammals

Marsupials

148

Beginnings of our XY

Humanmice

milli

on ye

ars

105

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

Sex chromosomes in weird animals

kangaroos are XX female, XY male

1 2 3 4 5 6 7 X Y

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

Y

X

Origin of human XY

Elephant

XX

A

Kangaroo Human

Map orthologues of human X genes

Y

Chicken Platypus Kangaroo Elephant Human

X64

1qA

X

A

X

Origin of human XY

Platypus sex chromosomes

Platypus sex chromosomes?Female: 26 pairsFemale: 26 pairs

Platypus sex chromosomes?

X1 Y1 X2 Y2 X3 Y3 X4 Y4 X5 Y5? ? ? ? ? ? ? ? ? ?

Female: 26 pairsMale: 21 pairs + 10

The New York Times, December 2004

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

Genes on platypus sex chromosomesNo homology to human X

Platypus genome projectVeyrunes, Waters Gen. Res. 2008

Homology to chicken Z DMRT1

AMH

Y

Chicken Platypus Kangaroo Elephant Human

X64

1qA

X

A

X

Origin of human XY

Male FemaleZ Z Z W

Bird sex

W is a degraded ZChicken

Emu

No SRYSex gene is DMRT1

Temperature Sex Determination - TSDe.g. Crocodiles and marine turtles

Bird ZW = a turtle autosome

Chick Z paint

6

6

Epigenetic sex

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

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?

Will males disappear?

New sex determining genes?

Parthenogenic females?XXXXXXXXXXXXXXXX

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

What if XX spiny rat woman man

War of the sex genes

Infertility

–> species divergence

New hominid species?

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

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

Don’t laugh at weird animals

THE FAR SIDE Garry Larsen

MORAL

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