Pathogenic fungi genomics, evolution and epidemiology! John W. Taylor University of California Berkeley, USA

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1 Pathogenic fungi genomics, evolution and epidemiology! John W. Taylor University of California Berkeley, USA

2 Adaptation!

3 Divergence

4 Divergence Adaptation

5 Darwin 1859 Mendel

6 Darwin Mendel 1866 Modern Synthesis

7 Modern Synthesis of Evolutionary Theory Ronald A. Fisher and Theodosius Dobzhansky

8 Modern Synthesis of Evolutionary Theory Ronald A. Fisher and Theodosius Dobzhansky Enzyme Electrophoresis 2010

9 Modern Synthesis of Evolutionary Theory Motoo Kimura, Neutral Evolution Enzyme Electrophoresis 2010

10 Modern Synthesis of Evolutionary Theory Motoo Kimura, Neutral Evolution Genomics

11 Koonin s Proposals on Evolution

12 Koonin s Proposals on Evolution

13 Koonin s Proposals on Evolution Trends in Genetics 25:473-5

14 Koonin s Proposals on Evolution Genomics Gene family expansion and contraction Gene duplication Gene loss Horizontal Gene Transfer Positive selection on single nucleotide variation is not dominant

15 Koonin s Proposals on Evolution Genomics Gene family expansion and contraction Gene duplication Gene loss Horizontal Gene Transfer Positive selection on single nucleotide variation is not dominant

16 Koonin s Proposals on Evolution Genomics Gene family expansion and contraction Gene duplication Gene loss Horizontal Gene Transfer Positive selection on single nucleotide variation is not dominant

17 There are hundreds of fungal genomes fungalgenomes.org

18

19 Gene duplication

20 Coccidioides Millions of years Berbee and Taylor 2010 Fungal Biology Reviews

21 Most fungi eat plants. Laetiporous sulphureus

22 Some fungi eat animals. Pocket mouse Perognathus spp. Kangaroo Rat Dipodomys spp.

23 hift of ubstrate rom plants o animals Basidiomycota Ascomycota Arabidopsis rice Puccinia graminis Ustilago maydis Cryptococcus neoformans Phanerochaete chrysosporium Coprinopsis cinerea Laccaria lacata Schizosaccharomyces pombe Saccharomyces cerevisiae Candida glabrata Yarrowia lipolytica Tuber melanosporum Fusarium graminearum Magnaporthe grisea Neurospora crassa Coccidioides immitis Aspergillus nidulans Rhizopus arrhizus sponge fish chicken human fruit fly mosquito nematode collar flagellate Millions of years 250 0

24 Genome Research

25 Gene Family Subtilisin N Peptidase S8 APH Peptidase M35 Expansions A. nidulans A. fumigatus A. terreus H. capsulatum U. reesii C. immitis C. posadasii N. crassa Sharpton et al F. graminearum * *

26 Keratin, hair, skin & connective tissue

27 Species

28 Species

29 Gene

30 Gene duplication

31 Peptidase S8 domain

32 No gene duplication Aspergillus oryzae Aspergillus oryzae Aspergillus flavus Uncinocarpus Coccidioides immitis Coccidioides posadasii Aspergillus nidulans Sclerotinia Botrytis Stagonospora Magnaporthe Trichoderma Peptidase S8 domain One fungus, one gene

33 Peptidase S8 domain

34 Gene family expansion * * * * * * * * * * Just three fungi: Coccidioides immitis Coccidioides posadasii Uncinocarpus reesei

35 Saccharomyces Millions of years Berbee and Taylor 2010 Fungal Biology Reviews

36

37 Saccharomyces has two almost identical ribosomal protein genes, RPL20A and RPL20B.

38 Saccharomyces has two almost identical ribosomal protein genes, RPL20A and RPL20B. ΔRPL20A strains grow slowly

39 Saccharomyces has two almost identical ribosomal protein genes, RPL20A and RPL20B. ΔRPL20A strains grow slowly... until RPL20B duplicates. 36 hrs

40 Saccharomyces has two almost identical ribosomal protein genes, RPL20A and RPL20B. RPL20B Chr XV Koszul et al EMBO J Duplications

41 Horizontal Gene Transfer

42 Gene

43 Gene Flow

44 Pyrenophora/Stagonospora Millions of years Berbee and Taylor 2010 Fungal Biology Reviews

45 Pyrenophora and Stagonospora cause disease of wheat fortheloveofseitan.com

46 Pyrenophora tritici-repentis tan spot of wheat.

47 Stagonospora Pyrenophora

48 Stagonospora Pyrenophora

49 Stagonospora Pyrenophora

50 Stagonospora Pyrenophora

51 Stagonospora Pyrenophora

52 Neurospora Millions of years Berbee and Taylor 2010 Fungal Biology Reviews

53

54

55 One Neurospora crassa population?

56 Caribbean llison et al PNAS Louisiana

57 Caribbean llison et al PNAS Louisiana

58 Two recently diverged populations Temperature: 9 C difference in mean annual minimum temperature (5 C vs 14 C) Latitude: degree difference in latitude llison et al PNAS

59 llison et al PNAS Chromosome 3 Speciation Island

60 llison et al PNAS Chromosome 3 Speciation Island

61 Chromosome 3 Speciation Island MRH4-like! ATP-dependent RNA helicase MRH4, mitochondrial!

62 Chromosome 3 Speciation Island MRH4-like! ATP-dependent RNA helicase MRH4, mitochondrial! Hunger et al J Bacteriol.

63 llison et al PNAS Chromosome 7 Speciation Island

64 Chromosome 7 Speciation Island! Prefoldin, a Chaperone that Delivers Unfolded Proteins to Cytosolic Chaperonin llison et al PNAS

65 Two recently diverged populations Temperature: 9 C difference in mean annual minimum temperature (5 C vs 14 C) Latitude: degree difference in latitude llison et al PNAS

66 llison et al PNAS

67 llison et al PNAS

68

69 Sex and Recombination

70 Saccharomyces Millions of years Berbee and Taylor 2010 Fungal Biology Reviews

71

72 Mild Adaptation Harsh Adaptation Clonal Sexual

73 oddard et al Nature

74 Aspergillus Millions of years Berbee and Taylor 2010 Fungal Biology Reviews

75 A. fumigatus recombines in nature

76

77 Koonin s Proposals on Evolution Genomics Gene family expansion and contraction Gene duplication Gene loss Horizontal Gene Transfer Positive selection on single nucleotide variation is not dominant

78 Koonin s Proposals on Evolution Genomics Gene family expansion and contraction Gene duplication Gene loss Horizontal Gene Transfer Positive selection on single nucleotide variation is not dominant

79 Koonin s Proposals on Evolution Genomics Gene family expansion and contraction Gene duplication Gene loss Horizontal Gene Transfer Positive selection on single nucleotide variation is not dominant

80 Koonin s Proposals on Evolution Positive selection on single nucleotide variation is not dominant

81 Koonin s Proposals on Evolution Positive selection on single nucleotide variation is not dominant

82 Pathogenic fungi genomics, evolution and epidemiology!

83

84

85

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90 Santa Fe Community Convention Center Santa Fe New Mexico USA January 15 20, 2012 Fungal Pathogens: From Basic Biology to Drug Discovery Part of the Keystone Symposia Global Health Series; joint with Drug Discovery for Protozoan Parasites Scientific Organizers: Joseph Heitman, John Taylor and Leah E. Cowen Meeting Session Topics: Mechanisms of Virulence Host Responses to Fungal Pathogens Drug Discovery for Eukaryotic Pathogens and Parasites Evolution and Comparative Genomics of Fungal Pathogens Cell Circuitry and Adaptive Responses Population Genetics and Genomics of Fungal Pathogens Drug Resistance/Antifungal Strategies and Resistance Mechanisms Sex, Cell Identity and Virulence Deadlines: Global Health Travel Award August 16, 2011 Abstract & Scholarship September 19, 2011 Early Registration November 15, 2011 Keystone Symposia is a 501(c)3 nonprofit directed and supported by the scientific community. Conferences provide an opportunity for debate, exchange and learning combined with leisure activities in world-class settings

91 Mycological Society of America Annual Meeting Fairbanks, Alaska, August 2 5,

92 Questions?

93 FGSC Chang-Lin Tien Graduate Fellowship

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