Weird animal genomes and sex chromosome evolution

Transcription

1 Weird animal genomes and sex chromosome evolution Genomes of distantly related mammals, other vertebrates Sex chromosome origins, evolution, fate Evolution of X and Y genes Jenny Graves La Trobe University, Melbourne, Australia (Paper co-edited with the European Cytogeneticists Association) Sequence is not enough!

2

3

4 Kangaroo genome project Model kangaroo -Tammar wallaby Macropus eugenii ~2.9 Gb, 1.5x WGS sequence, 454, BAC ends assembly

5 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

6 Gorgeous kangaroo chromosomes

7

8

9 Kangaroo-human comparative map Human chromosomes

10 Comparing marsupial genomes Isolate chromosomes from tammar wallaby Chromosome-specific DNA ( paints ) Hybridize to swamp wallaby Ferguson-Smith, Rens

11 Marsupial comparative chromosome painting X 2n = 18 opossum 2n = conserved complement - dunnart X 2n = 16 tammar

12

13

14 X chromosome paint Painting and mapping tumour chromosomes Deakin, Bender et al 2011

15

16

17 The platypus genome

18

19 Platypus mapping

20 Genome smallish (2.6 Gb) 6X WGS assembly Mammal, reptile genes milk genes egg yolk genes venom genes Warren et al, Nature 2007

21

22 Sequence all vertebrates (66,000 species) Both sexes!! Map at least one species in group

23 Sex and sex chromosomes

24

25 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

26

27 X Y Sex chromosomes > trouble SRY Problems at meiosis Dosage problems Sex-linked diseases Sex-reversal syndromes Why so weird? so they XXXXXXXXXXXXXXXXX work optimally? evolutionary accident? Dumb design!!

28 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

29

30 Origin of human sex chromosomes Amphibians Fish Reptiles and birds Monotremes Marsupials Placentals 310 Amniotes XY? Human Mouse Mammals Tetrapods

31

32

33

34

35 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

36 Relationship between X and Y 5 4 genes 12 genes 41 genes Y Y X X Kangaroo Human

37 Origin of human sex chromosomes Reptiles and birds? Monotremes Marsupials Placentals XY XY Amphibians Fish 310 Amniotes Mammals Tetrapods

38

39

40

41 1q 5 Y 4 X X Birds Kangaroo Human

42

43

44

45

46 Sex chromosome variation in reptiles Gekko Z= bird Z!! Bird Which ZW is ancestral? Gekko Z Rat snake 2 Turtle 6 Bird Z

47 Origin of human sex chromosomes Reptiles and birds TSD XY ZW? ZW ZW Monotremes Marsupials Placentals XY XY Amphibians Fish ZW 310 Amniotes Mammals Tetrapods

48 Platypus sex chromosomes? X 1 Y 1 X 2 Y 2 X 3 Y 3 X 4 Y 4 X 5 Y 5??????????

49 Identifying X and Y in platypus Paint E3 Paint E4 X Y X female male

50 The New York Times, December 2004

51

52 1q A A Y 4 6 X X Chicken Platypus Marsupial Human

53 Genes on platypus sex chromosomes No homology to human X Homology to chicken Z DMRT1 Veyrunes, Waters Gen. Res. 2008

54

55

56 Evolution of the X X Y lots of genes many different functions conserved in mammals (because of XCI?)

57 Functions of X chromosome genes Immaculate Controlling Smart Sexy X X X X Brains-and-balls genes

58 Evolution of the Y Only 45 genes Male-specific functions Poorly conserved X Y

59 Y chromosome models

60

61

62 Degradation of the Y High variation frequent mutation, deletion, insertion Inefficient selection/drift no recombination

63 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

64 Will males disappear? Parthenogenic XXXXXXXXXXXXXXXX females? New sex determining genes?

65

66

67

68 Conclusions Vertebrate genome is very conserved Different regions may become sex chromosomes Biased gene content, degeneration Need map as well as sequence!

69 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