Phylogenetics: The “E” word in disguise Keith A. Crandall, Brigham Young University

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Presentation transcript:

Phylogenetics: The “E” word in disguise Keith A. Crandall, Brigham Young University

Phylogeny - What is it? How do you reconstruct them? What are they good for? Is evolution important?

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 Over 14 million AIDS orphans

Where Did HIV Originate? Geographic location? Previous host? Timing of transmission?

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

Number of Trees?

HIV-1 Whole Genomes HIV-1 Whole Genomes 2003 (JAN) - 397

Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA

Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA

Working Tree sp1 sp4 sp2 sp3 sp5 c2

Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA

Working Tree sp1 sp4 sp2 sp3 sp5 c2 c4

Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA

Working Tree sp1 sp4 sp2 sp3 sp5 c2 c4 c7

Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA

Working Tree sp1 sp4 sp2 sp3 sp5 c2 c4 c7 c9

Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA

Working Tree sp1 sp4 sp2 sp3 sp5 c2 c4 c7 c9 c10

Estimate a Phylogeny Sp1ACCGTCTTGTTA Sp2AGCGTCATCAAA Sp3AGCGTCATCAAA Sp4ACCGTCTTGATA Sp5AGCCTCTTCATA

Final Tree sp1 sp4 sp2 sp3 sp5 c2 c4 c7 c9 c10 c11

Previous Host Phylogeny!

Why Estimating Phylogenetic Relationships? Designating Subtypes - Classification Establishing Transmission Patterns Evolution of Drug Resistance Estimating Population Genetic Parameters - Migration rates, Recombination rates, etc.

Transmission Patterns Louisiana Murder Trial Expectations? Samples from Victim Samples from patients of the accused Samples from local controls

V V P P LC V V P P or VS V V P P LC Alternative Hypotheses GUILTY!Not! VS

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

River One River Two Population Subdivision Single Species Phylogeography

River One Historical Isolation/ Fragmentation Recurrent Restricted Gene Flow Comparative Phylogeography

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

Phylogeny Cambarus hamulatus Cambarus jonesi Cambarus sp. nov. 1 Cambarus sp. nov. 2

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

Molecular Evolution

PHENOTYPE GENOTYPE ENVIRONMENT OPSIN: Model System for Molecular Evolution Wavelength (nm) UVIR CRLAKIAMTTVALWFIAWT PYLLINWVGMFARSYLSPV YTIWGYVFAKANAVYNPIV YAISHPKYRAAMEKKLPCL SCKTESDDVSESASTTTSS

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

Coil Tendencies, Compressibility, Alpha-Helix

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

Acknowledgements NSF Arkansas Game & Fish BYU Colleagues Students Family