jenny graves at smbe2014: sex, genes and sequence
DESCRIPTION
Jenny Graves talk at the Society for Molecular Biology and Evolution meeting in San Juan, Puerto Rico on "Sex, Genes and Sequence". June 9th 2014TRANSCRIPT
Sex, Genes and Sequence
Sex chromosomes – most interesting part of genome
Origins, evolution, future of X and Y
Epigenetics and environmental sex
Origins, evolution of sex genes
Jenny GravesLA Trobe University, ANU, U Canberra
Sex 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–> trouble
• the Y self-destructs!
X Y
proto-XY
XY evolutionOnce the X and Y were an ordinary pair
One partner acquires a male-determining gene
Other male-advantage genes accumulate- recombination suppressed
Y degraded by deletion, mutation
And degraded and degraded
And can even disappear
The Y is a degraded XEvidence: XY homology; independent Y dropouts
Self-destruction of the Y
High variation
• frequent mutation, deletion, insertion
in testis
Inefficient selection and drift• no recombination, no repair
Rate of loss is ~10 genes/MYY will self-destruct in 4.6 mY
How the Y chromosome determines sex
female male
X X X Y
TDF
testis
hormones
=SRY
Y genes are degraded X genes
TSPYSpermatogenesis?
RBMYSpermatogenesis
Y
SRYSex determination
RBMXMental retardation?
X
SOX3Mental retardationspermatogenesis
TSPXCell cycle?
Most Y genes have copies on X
Brains-and-balls genes –> sex and fertility genes
X-Y shared dosage-sensitive genes in added region
Mammals
Fish450
Tetrapods
Amphibians
410
Monotremes
166
Amniotes
Birds andReptiles
310
Placentalmammals
Marsupials
148
Vertebrate relationships
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
???
Mammals
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
Male FemaleZ Z Z W
Bird sex
W is a degraded Z
Chicken
Emu
XY and ZW chromosomes follow the same evolutionary rules
X Y W Z
humansmice
kangaroos
ratite birds
carinate birds
male femaleZ Z Z W
What is the bird sex-determining gene?No SRY
Dose-dependent sex determination
DMRT1 on Z but not W
Need two doses to make enough male-determining productKnockdown –> ZZ female
Platypus sex chromosomes
X1 Y1 X2 Y2 X3 Y3 X4 Y4 X5 Y5
Female: 26 pairsMale: 21 pairs + 10
Homology to chick ZWNo homology to human XY
No SRYAMH Sex determining?
Mammals
Amniotes
Tetrapods
Fish
Amphibians
Reptiles and birds Monotremes Marsupials Placentals
450
410
310
166148
XYXYTSD,XY,ZW XY ZW
XYXYXYXYXY
Origin of human sex chromosomes
ZW?
SRY
XY and ZW chromosomes follow the same evolutionary rules
X Y W Z
humansmice
kangaroos
ratite birds
carinate birds
boid snakes
colubrid snakes
vipers
Snake sex chromosomes
Vicoso et al, PLoS Biol 2013
Coverage for male ZZ (blue) and female ZW (red)Assembled against Anolis macrochromosomes 1-6
Conserved ZBoids show no ZW differentiationColubrids and viperids show extreme ZW differentiation
Snakes are ZZ male / ZW female
Snake Z = chicken 2
SOX34
2
5
TSD turtle Birds Platypus Kangaroo HumanSnakes1
DMRT1
SOX34
ZW
2
1
DMRT1
SOX3SRY
X Y
4
3,7,10
SOX3
SRYX Y
5
1
3
SOX3
6
15, 18
DMRT1
X Y X Y X Y X Y X Y
?
DMRT1
SOX34
2
ZW
1
Different genome regions became sex chromosomes in different vertebrates
Sex in frogsYoshimoto & Ito, FEBS J 2011
Conclude DMW inhibits DMRT12 DMRT1 –> male2 DMRT1 + DMW –> femaleDMW defines new W
Xenopus laevis has ZZ / ZW Found DMRT1 homologue on WDMW knockdown –> ZW males
ZW=XY=human XqSOX3 is sex determining
Rana rugosa has ZZ / ZW and XY / XX
Miura et al 2010
Sex in FishLinkage analysis –> chr 1=XYY Positional cloning –>DMRT1 copy
XX female XX+DMY male XY male
Transgenic DMY –> XX male
Matsuda et al, Nature 2002; PNAS 2007
soma testis
Conclude:2 DMRT1 female2 DMRT1 + DMY maleDMY defines a new Y
Medaka Oryzias latipes
MALE FEMALEZ Z
X Y
Z ZZ W
X X
Z W
A A
A A
A A
A A
Neo-Y
Neo-W
Origin of new sex genes?
from copy
from inactive copy
Sex in other medaka species
O. latipes LG1 DMY
O. curvinotos LG1 DMY
=> Change in expression level or timing
O. dancera LG10 ?
Oda (XY=LG10)Sox3 on X, Y –> same protein
Overexpression of Sox3 –>male
Olu ( XY=LG12)Gsdf on X, Y–>same protein Overexpression of GsdfY –>male
O. luzonensis LG12 ?
Ope (XY=LG12)Gsdf on X, Y–>same protein Early expression of GsdfbY –>male
O. pectoralis LG12 ?
A A
A A
X Y
X Y
A A
A A
Z W
Z W Overexpression of one allele
MALE FEMALE
testis ovary
New sex genes from expression change
testis ovary
Change in timing or tissue of expression
Ectopic expression in testis–>XX males
SOX3active in brain, germ-cells
Evolution of SRY
Fusion
expression in gonad
SRYtestis determination
New function
Sato et al Mol Cell Biol 2010; Sutton et al J Clin Invest 2011
Mammals
Amniotes
Tetrapods
Fish
Amphibians
Reptiles and birds Monotremes Marsupials Placentals
450410
310
166148
XYXYTSD,XY,ZW XY ZW
XYXYXYXYXY
Independent recruitment of sex genes
MY
DMYO. latipes
DMWX. laevis
DMRT1birds
SRY
SOX3
SOX3R. rugosa
SOX3O. dancera
AMHsea bass
AMH?
DMRT1tongue sole
Mammals
Temperature Sex Determination - TSDe.g. Crocodiles and marine turtles
No sex chromosomes
Chick Z
6
6
Dragon lizard Pogona vitticeps
%m
ales
Temperature –>
50
0
GSD TSDIdentification of ZW by CGH
W
Quinn et alScience ‘07
A dragon with ZW and TSD
GSD–> TSDZW –> XY
male femaleZ Z Z W
Normaltemperature
female femaleZ Z Z W
Hightemperature
Sex in dragons
Finding dragon sex determining gene….
dose-dependent
and temperature-dependent
Microdissected W, screened for W BACs Sequenced W BAC –> RCC1, OPRD1, syntenic with RSPO1…Sequenced ZZ male, ZW female, ZZ female at BGI
ZZ ZW ZWmale female pseudomale
dmrt1 dmrt1 dmrt1
Epigenetic sex determinationHalf smooth tongue soleChen et al Nature, Shao et al Genome Res
AUTOSOMES SEX CHROMOSOMES
methylation
Conclusions
Vertebrate genome is very conserved
Different genome regions became sex chromosomes
New sex genes evolve, often from same autosomal gene
Sex chromosomes specialize, then self-destruct
Sex can be determined or modified by environment