Weird animal genomes and sex chromosome evolution

Weird animal genomes and sex chromosome evolution

Weird animal genomes and
sex chromosome evolution
Jenny Graves
La Trobe University, Melbourne, Australia
(Paper co-edited with the European Cytogeneticists Association)
Genomes of distantly related mammals, other vertebrates
Sex chromosome origins, evolution, fate
Evolution of X and Y genes
Sequence is not enough!
Kangaroo genome project
• Model kangaroo -Tammar wallaby Macropus eugenii
• ~2.9 Gb, 1.5x WGS sequence, 454, BAC ends
• assembly
Kangaroo linkage map
• island populations
many genetic differences
• hybrids, backcrosses
• map construction
microsatellites (random, targeted genes)
• phenotypes
e.g. pest resistance
toxin resistance (1080)
milk characters
Gorgeous kangaroo chromosomes…
Kangaroo-human comparative map
Human chromosomes
Comparing marsupial genomes
Isolate chromosomes
from tammar wallaby
Chromosome-specific
DNA (“paints”)
Hybridize to
swamp wallaby
Ferguson-Smith, Rens
Marsupial comparative chromosome painting
1
2
3
4
5
6
7
8
7
X
2n = 18 opossum
2n ==14
2n
14 conserved complement - dunnart
1
2
2n = 16 tammar
3
4
5
6
X
X chromosome paint
Painting and mapping
tumour chromosomes
Deakin, Bender et al 2011
The platypus genome
Platypus mapping
Genome
• smallish (2.6 Gb)
• 6X WGS assembly
Mammal, reptile genes
•  milk genes
•  egg yolk genes
•  venom genes
Warren et al, Nature 2007
• Sequence all vertebrates (66,000 species)
• Both sexes!!
• Map at least one species in group
Sex and sex chromosomes
Identity of the testis determining gene?
Jamie Foster, Andrew Sinclair
ZFY is in the wrong place
ZFY is the wrong gene!
SRY is the right gene
SOX3 ancestor of SRY
Sex chromosomes –> trouble
SRY
X Y
• Problems at meiosis
• Dosage problems
• Sex-linked diseases
• Sex-reversal syndromes
Why so weird?
• so they
work optimally?
XXXXXXXXXXXXXXXXX
• evolutionary accident?
Dumb design!!
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
X
Y
The Y is a degraded X
Origin of human sex chromosomes
Reptiles and birds
Monotremes Marsupials Placentals
?
XY
Human
Mouse
105
148
166
Mammals
Amphibians
Fish
310
Amniotes
410
450
Tetrapods
Genes on kangaroo Y
• Microdissect Y, make DNA
• Use to screen BACs
• Map
• Sequence
• 12 new genes
• All on tiny Yp
• 11 have copies on X
Different Y genes, same rules
Relationship between X and Y
5
4 genes
41 genes
12 genes
Y
Y
X
Kangaroo
X
Human
Origin of human sex chromosomes
Reptiles and birds
?
Monotremes Marsupials Placentals
XY
XY
148
166
Mammals
Amphibians
Fish
310
Amniotes
410
450
Tetrapods
1q
5
Y
4
Birds
X
Kangaroo
X
Human
Sex chromosome variation in reptiles
Gekko Z= bird Z!!
Gekko
Z
Bird
Which
ZW is ancestral?
Rat snake
2
Turtle
6
Bird
Z
Origin of human sex chromosomes
Reptiles and birds
TSD XY ZW
ZW ZW
Amphibians
Monotremes Marsupials Placentals
?
XY
148
166
Mammals
ZW
Fish
310
Amniotes
410
450
XY
Tetrapods
Platypus sex chromosomes?
?
X1
?
Y1
? ?
X2
Y2
?
X3
? ? ? ? ?
Y3
X4
Y4
X5 Y5
Identifying X and Y in platypus
Paint E3
Paint E4
X Y X
female
male
The New York Times, December 2004
1q
A
A
Y
4
Chicken
6
Platypus
X
Marsupial
X
Human
Genes on platypus sex chromosomes
No homology to human X
Homology to chicken Z
DMRT1
Veyrunes, Waters Gen. Res. 2008
Evolution of the X
• lots of genes
• many different functions
• conserved in mammals
X
Y
(because of XCI?)
Functions of X chromosome genes
Immaculate
X
Controlling
X
Smart
X
Sexy
X
Brains-and-balls genes
Evolution of the Y
Only 45 genes
Male-specific functions
Poorly conserved
X
Y
Y chromosome models
Degradation of the Y
High variation
• frequent mutation, deletion, insertion
Inefficient selection/Drift
• no recombination
The future of sex
When will our Y disappear?
166 MYA – the Y had 1669 genes
Today – the Y has 45
Genes lost per MY = ~1624/166 = ~9.8
At this rate Y will disappear in 4.6 MY
Will males disappear?
Parthenogenic females?
XXXXXXXXXXXXXXXX
New sex determining genes?
Conclusions
Vertebrate genome is very conserved
Different regions may become sex chromosomes
Biased gene content, degeneration
Need map as well as sequence!
Graves lab
Sex and Y team
Andrew Sinclair
Jamie Foster
Francine Brennan
Patrick Western
Rob Glas
Swathi Shetty
Andrew Pask
Roland Toder
Rachael O’Neill
Margaret Delbridge
Paul Waters
Janine Deakin
Frank Grützner
Mary Wallis
Tariq Ezaz
Veronica Murtagh
Denis O’Meally
Liz Murchison
Claudia Delgano
Collaborators
Georges, Sarre
U. Canberra
Fujiyama, Kuroki
NIG, RIKEN
Marilyn Renfree
Univ. Melbourne
Malcolm Ferguson-Smith Cambridge
Friendly Genome Centres
Wash U `
Wes Warren
JGI
Jeff Boore, Gerry Rubin
Sanger
Mark Ross