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

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Transcription:

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

Adaptation!

Divergence

Divergence Adaptation

Darwin 1859 Mendel 1866 1830 1850 1870 1890 1910 1930 1950 1970 1990 2010

Darwin 1859 + Mendel 1866 Modern Synthesis 1830 1850 1870 1890 1910 1930 1950 1970 1990 2010

Modern Synthesis of Evolutionary Theory Ronald A. Fisher and Theodosius Dobzhansky 1830 1850 1870 1890 1910 1930 1950 1970 1990 2010

Modern Synthesis of Evolutionary Theory Ronald A. Fisher and Theodosius Dobzhansky 1830 1850 1870 1890 1910 1930 1950 1970 1990 Enzyme Electrophoresis 2010

Modern Synthesis of Evolutionary Theory Motoo Kimura, Neutral Evolution 1830 1850 1870 1890 1910 1930 1950 1970 1990 Enzyme Electrophoresis 2010

Modern Synthesis of Evolutionary Theory Motoo Kimura, Neutral Evolution 1830 1850 1870 1890 1910 1930 1950 1970 1990 2010 Genomics

Koonin s Proposals on Evolution

Koonin s Proposals on Evolution

Koonin s Proposals on Evolution 2009. Trends in Genetics 25:473-5

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

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

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

There are hundreds of fungal genomes fungalgenomes.org

Gene duplication

Coccidioides Millions of years Berbee and Taylor 2010 Fungal Biology Reviews

Most fungi eat plants. Laetiporous sulphureus

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

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 1250 1000 750 500 Millions of years 250 0

Genome Research. 2009. 19 1722-1731.

Gene Family Subtilisin N Peptidase S8 APH Peptidase M35 Expansions A. nidulans 2 3 3 9 A. fumigatus 2 5 2 9 A. terreus 2 6 2 29 H. capsulatum 2 6 1 20 U. reesii 15 19 4 33 C. immitis 13 16 7 38 C. posadasii 14 16 7 32 N. crassa 3 6 2 6 Sharpton et al. 2009 F. graminearum 11 24 1 15 * *

Keratin, hair, skin & connective tissue www.privemillenia.com

Species

Species

Gene

Gene duplication

Peptidase S8 domain

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

Peptidase S8 domain

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

Saccharomyces Millions of years Berbee and Taylor 2010 Fungal Biology Reviews

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

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

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

Saccharomyces has two almost identical ribosomal protein genes, RPL20A and RPL20B. RPL20B Chr XV Koszul et al. 2004. EMBO J Duplications

Horizontal Gene Transfer

Gene

Gene Flow

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

Pyrenophora and Stagonospora cause disease of wheat fortheloveofseitan.com

Pyrenophora tritici-repentis tan spot of wheat.

Stagonospora Pyrenophora

Stagonospora Pyrenophora

Stagonospora Pyrenophora

Stagonospora Pyrenophora

Stagonospora Pyrenophora

Neurospora Millions of years Berbee and Taylor 2010 Fungal Biology Reviews

One Neurospora crassa population?

Caribbean llison et al. 2011. PNAS Louisiana

Caribbean llison et al. 2011. PNAS Louisiana

Two recently diverged populations Temperature: 9 C difference in mean annual minimum temperature (5 C vs 14 C) Latitude: 2.4-10.6 degree difference in latitude llison et al. 2011. PNAS

llison et al. 2011. PNAS Chromosome 3 Speciation Island

llison et al. 2011. PNAS Chromosome 3 Speciation Island

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

Chromosome 3 Speciation Island MRH4-like! ATP-dependent RNA helicase MRH4, mitochondrial! Hunger et al. 2006. J Bacteriol.

llison et al. 2011. PNAS Chromosome 7 Speciation Island

Chromosome 7 Speciation Island! Prefoldin, a Chaperone that Delivers Unfolded Proteins to Cytosolic Chaperonin llison et al. 2011. PNAS

Two recently diverged populations Temperature: 9 C difference in mean annual minimum temperature (5 C vs 14 C) Latitude: 2.4-10.6 degree difference in latitude llison et al. 2011. PNAS

llison et al. 2011. PNAS

llison et al. 2011. PNAS

Sex and Recombination

Saccharomyces Millions of years Berbee and Taylor 2010 Fungal Biology Reviews

Mild Adaptation Harsh Adaptation Clonal Sexual

oddard et al. 2005 Nature

Aspergillus Millions of years Berbee and Taylor 2010 Fungal Biology Reviews

A. fumigatus recombines in nature

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

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

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

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

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

Pathogenic fungi genomics, evolution and epidemiology!

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. www.keystonesymposia.org/12j2 1-800-253-0685 1-970-262-1230

Mycological Society of America Annual Meeting Fairbanks, Alaska, August 2 5, 2011 WWW.MSAFUNGI.ORG

Questions?

FGSC Chang-Lin Tien Graduate Fellowship