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Phylogenetics: The “E” word in disguise Keith A. Crandall, Brigham Young University http://biology.byu.edu/Faculty/kac/crandall_lab/
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Phylogeny - What is it? How do you reconstruct them? What are they good for? Is evolution important?
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Molecular Evolution of HIV: A teaching model for evolution Over 22 million people have died from AIDS Over 42 million people are living with HIV/AIDS - 74% in sub-Saharan Africa Over 19 million women are living with HIV/AIDS 14,000 new infections every day (half occurring among people ages 15-24 Over 14 million AIDS orphans
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Where Did HIV Originate? Geographic location? Previous host? Timing of transmission?
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Group O Group M HIV Type 2 Type 1 HIV-1 and HIV-2 HIV-1 group O and M HIV-1 group M Geographic Origins & Distribution of HIV
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Number of Trees?
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HIV-1 Whole Genomes 1993 - 15 HIV-1 Whole Genomes 2003 (JAN) - 397
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Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA
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Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA
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Working Tree sp1 sp4 sp2 sp3 sp5 c2
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Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA
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Working Tree sp1 sp4 sp2 sp3 sp5 c2 c4
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Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA
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Working Tree sp1 sp4 sp2 sp3 sp5 c2 c4 c7
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Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA
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Working Tree sp1 sp4 sp2 sp3 sp5 c2 c4 c7 c9
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Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA
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Working Tree sp1 sp4 sp2 sp3 sp5 c2 c4 c7 c9 c10
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Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA
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Final Tree sp1 sp4 sp2 sp3 sp5 c2 c4 c7 c9 c10 c11
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Previous Host Phylogeny!
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Why Estimating Phylogenetic Relationships? Designating Subtypes - Classification Establishing Transmission Patterns Evolution of Drug Resistance Estimating Population Genetic Parameters - Migration rates, Recombination rates, etc.
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Transmission Patterns Louisiana Murder Trial Expectations? Samples from Victim Samples from patients of the accused Samples from local controls
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V V P P LC V V P P or VS V V P P LC Alternative Hypotheses GUILTY!Not! VS
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Genetic Questions What is this? - DNA Barcoding Where did it come from? When did it get here? What’s its function? Molecular, Ecological, Phenotypic Correlations between form and function Correlations between genotype and phenotype
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River One 122 10 1741405 16 8 3 13 9 0011 River Two Population Subdivision Single Species Phylogeography
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River One 12 2 10 1741405 16 8 3 13 9 0011 Historical Isolation/ Fragmentation Recurrent Restricted Gene Flow 8 3 5 7 4 11 12 9 613 2 10 1000140 Comparative Phylogeography
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Southern Appalachian species Western Escarpment Sequatchie Valley Jackson County Mountains Highland Rim Cambarus hamulatus Cambarus jonesi Cambarus sp. nov. 1 Cambarus sp. nov. 2 Cambarus veitchorum Sampled site
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Phylogeny 86 77 97 85 74 42 68 44 84 38 86 75 82 100 55 100 99 58 48 100 91 65 100 97 100 93 99 Cambarus hamulatus Cambarus jonesi Cambarus sp. nov. 1 Cambarus sp. nov. 2
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Genealogy 1-2, 1-5 CRE 2-1 LDC 2-3 RGF w/ IBD 2-6, 3-1, 3-3 CRE 3-2 LDC Total PF & LDC
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Molecular Evolution
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PHENOTYPE GENOTYPE ENVIRONMENT OPSIN: Model System for Molecular Evolution Wavelength (nm) 400500600700 UVIR CRLAKIAMTTVALWFIAWT PYLLINWVGMFARSYLSPV YTIWGYVFAKANAVYNPIV YAISHPKYRAAMEKKLPCL SCKTESDDVSESASTTTSS
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Is max Correlated with Ecological Differences? microscopic thin beam of spectral light INPUTOUTPUT INPUT – OUTPUT = pigment absorbance Detect light not absorbed by the photopigment 400 – 700 nm at 1nm intervals
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Coil Tendencies, Compressibility, Alpha-Helix
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Summary Evolutionary histories provide great insights into the biology of infectious diseases Indeed, we use these same approaches in conservation genetics, endangered species studies, etc. HIV provides a unique model system for teaching evolution since you can experience evolution in real time Research Experience - GET SOME! NSF RET - Research Experience for Teachers
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Acknowledgements NSF Arkansas Game & Fish BYU Colleagues Students Family
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