Jenny Graves at SMBE2014: Sex, Genes and Sequence
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Jenny Graves talk at the Society for Molecular Biology and Evolution meeting in San Juan, Puerto Rico on "Sex, Genes and Sequence". June 9th 2014
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Jenny Graves at SMBE2014: Sex, Genes and Sequence
- 1. 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 Graves LA Trobe University, ANU, U Canberra
- 2. Sex chromosomes are weird X 1669 genes Many different functions Many sex, intelligence genes Brains-and-balls genes Y Only 27 genes specific to Y Many copies, pseudogenes Male-specific functions Sex and spermatogenesis PAR Shared by X and Y Contains 24 genes Smart, Sexy X Wimpy Y
- 3. • Problems at meiosis • Dosage problems • Sex-linked diseases • Sex-reversal syndromes Why so weird? • so they work optimally? • evolutionary accident? XXXXXXXXXXXXXXXXX X Y Dumb Sex chromosomes –> trouble • the Y self-destructs!
- 4. X Y proto-XY XY evolution Once 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 X Evidence: XY homology; independent Y dropouts
- 5. 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/MY Y will self-destruct in 4.6 mY
- 6. How the Y chromosome determines sex female male X X X Y TDF testis hormones =SRY
- 7. Y genes are degraded X genes TSPY Spermatogenesis? RBMY Spermatogenesis Y SRY Sex determination RBMX Mental retardation? X SOX3 Mental retardation spermatogenesis TSPX Cell 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
- 9. Mammals Amniotes Tetrapods Fish Amphibians Reptiles and birds Monotremes Marsupials Placentals 450 410 310 166 148 XY Origin of human sex chromosomes Human Mouse 105 X ? Elephant ??? Mammals
- 10. Y X Origin of human XY Elephant XX A Kangaroo Human Map orthologues of human X genes
- 11. Y Chicken Platypus Kangaroo Elephant Human X64 1q A X A X Origin of human XY
- 12. Male Female Z Z Z W Bird sex W is a degraded Z Chicken Emu
- 13. XY and ZW chromosomes follow the same evolutionary rules X Y W Z humans mice kangaroos ratite birds carinate birds
- 14. male female Z 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 product Knockdown –> ZZ female
- 15. Platypus sex chromosomes X1 Y1 X2 Y2 X3 Y3 X4 Y4 X5 Y5 Female: 26 pairsMale: 21 pairs + 10 Homology to chick ZW No homology to human XY No SRY AMH Sex determining?
- 16. Mammals Amniotes Tetrapods Fish Amphibians Reptiles and birds Monotremes Marsupials Placentals 450 410 310 166 148 XYXYTSD,XY,ZW XY ZW XYXYXYXYXY Origin of human sex chromosomes ZW? SRY
- 17. XY and ZW chromosomes follow the same evolutionary rules X Y W Z humans mice kangaroos ratite birds carinate birds boid snakes colubrid snakes vipers
- 18. 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 Z Boids show no ZW differentiation Colubrids and viperids show extreme ZW differentiation Snakes are ZZ male / ZW female Snake Z = chicken 2
- 19. SOX3 4 2 5 TSD turtle Birds Platypus Kangaroo HumanSnakes 1 DMRT1 SOX3 4 ZW 2 1 DMRT1 SOX3 SRY X Y 4 3,7,10 SOX3 SRY X Y 5 1 3 SOX3 6 15, 18 DMRT1 X Y X Y X Y X Y X Y ? DMRT1 SOX3 4 2 ZW 1 Different genome regions became sex chromosomes in different vertebrates
- 20. Sex in frogs Yoshimoto & Ito, FEBS J 2011 Conclude DMW inhibits DMRT1 2 DMRT1 –> male 2 DMRT1 + DMW –> female DMW defines new W Xenopus laevis has ZZ / ZW Found DMRT1 homologue on W DMW knockdown –> ZW males ZW=XY=human Xq SOX3 is sex determining Rana rugosa has ZZ / ZW and XY / XX Miura et al 2010
- 21. Sex in Fish Linkage analysis –> chr 1=XY Y 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 female 2 DMRT1 + DMY male DMY defines a new Y Medaka Oryzias latipes
- 22. MALE FEMALE Z Z X Y Z Z Z 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
- 23. 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 ?
- 24. 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
- 25. Ectopic expression in testis –>XX males SOX3 active in brain, germ-cells Evolution of SRY Fusion expression in gonad SRY testis determination New function Sato et al Mol Cell Biol 2010; Sutton et al J Clin Invest 2011
- 26. Mammals Amniotes Tetrapods Fish Amphibians Reptiles and birds Monotremes Marsupials Placentals 450 410 310 166 148 XYXYTSD,XY,ZW XY ZW XYXYXYXYXY Independent recruitment of sex genes M Y DMY O. latipes DMW X. laevis DMRT1 birds SRY SOX3 SOX3 R. rugosa SOX3 O. dancera AMH sea bass AMH? DMRT1 tongue sole Mammals
- 27. Temperature Sex Determination - TSD e.g. Crocodiles and marine turtles No sex chromosomes Chick Z 6 6
- 28. Dragon lizard Pogona vitticeps %males Temperature –> 50 0 GSD TSD Identification of ZW by CGH W Quinn et al Science ‘07 A dragon with ZW and TSD GSD–> TSD ZW –> XY
- 29. male female Z Z Z W Normal temperature female female Z Z Z W High temperature 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
- 30. ZZ ZW ZW male female pseudomale dmrt1 dmrt1 dmrt1 Epigenetic sex determination Half smooth tongue sole Chen et al Nature, Shao et al Genome Res AUTOSOMES SEX CHROMOSOMES methylation
- 31. 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