DNA in Hollywood: Fact, Fiction And

Hot Science - Cool Talk # 49 DNA in Hollywood: Fact, Fiction, and Future

Dr. David Hillis September 14, 2007

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David M. Hillis Section of Integrative Biology & Center for Computational Biology The University of Texas at Austin CSI clip Phylogenetic analysis can be used to trace viral infections through a human population

• Origins of HIV, SARSand other viruses transmitted between animals and humans • Global virus diversity for vaccine trials • Epidemiological studies • Identification of new diseases • Forensic uses Phylogeny Papers, 1981-2006 (with “phylogeny” or “phylogenetic” in title or abstract)

9000

8000

7000

6000

5000

4000

3000

2000 Number of papers per year

1000

0 1980 1985 1990 1995 2000 2005 Year of publication Phylogeny Evolutionary relationships among lineages, such as genes, individuals, populations, species, etc. Time

Consider an ancestral lineage (e.g., descendants from one HIV virus) Phylogeny Evolutionary relationships among lineages, such as genes, individuals, populations, species, etc. Time

One lineage splits into two by mutation Phylogeny Evolutionary relationships among lineages, such as genes, individuals, populations, species, etc. Time There are now two HIV lineages Phylogeny Evolutionary relationships among lineages, such as genes, individuals, populations, species, etc.

Some lineages become extinct

x Time

Lineages continue to diversify through time Phylogeny Evolutionary relationships among lineages, such as genes, individuals, populations, species, etc.

x Time

The relationships among lineages produce a phylogenetic tree Phylogeny Evolutionary relationships among lineages, such as genes, individuals, populations, species, etc.

If samples are taken at this point in time…

x …then the reconstructed phylogenetic tree will Time look like this Phylogeny How is evolutionary history reconstructed?

Time Each of these tick marks represents a new mutation in the genome of the respective HIV lineage Phylogeny How is evolutionary history reconstructed?

1 2 3 4 5 6

Lineages x 1 and 2 will share these mutations Time Phylogeny How is evolutionary history reconstructed?

1 2 3 4 5 6

Time Lineages 1, 2, 3, and 4 will share these mutations Phylogeny How is evolutionary history reconstructed?

A model of HIV evolution is used to account for multiple changes to Time the same sites on a genome, different rates of changes among sites, and other details of HIV evolution How do we know phylogenetic analysis works? Experimental evolution to test phylogenetic methods

9 1 2 3 4 5 6 7 8

ancestral nodes

internode distance = -400 generations T7 (wild type) (40 serial transfers)

Hillis et al., 1992 (Science 255:589-592)3 HIV transmission

Viral transmission events may be traced back through time among individuals in a population.

To imagine how this is possible, start by considering the diversity of HIV within one infected individual:

Time 1: Prior to Transmission event

HIV sequence sampled from source At the transmission event, the HIV in the recipient represents a small subset of the HIV in the source:

Time 2: The transmission event

To recipient HIV sequence sampled from source As time passes, HIV lineages in the source and recipient diversify, and other lineages become extinct.

Time 3: Shortly after transmission event

HIV from recipient HIV sequence sampled from source x x x Immune system has x x x x terminated the lineage Time of transmission After enough time has passed, immunoselection will result in an apparent sister-group relationship among the HIV lineages in the source and recipient:

Time 4: Further after transmission event

HIV sequence sampled HIV from from source recipient

x x x x x x x x x x x x x x x Time of transmission patient.a P3.BCM P4.MIC patient.b P5.BCM victim.a P6.MIC V1.BCM victim.b V2.BCM patient.c V1.MIC V2.MIC patient.d Transmission from P6.BCM patient.e P4.BCM patient to victim P1.BCM patient.f P7.BCM patient.g P5.MIC P2.BCM LA08.RT P2.MIC LA02.RT P3.MIC P1.MIC LA05.RT LA32.RT New sequences added LA06.RT LA12.RT LA18.RT LA30.RT LA27.RT LA23.RT LA07.RT LA28.RT LA25.RT LA04.RT LA21.RT LA24.RT Phylogenetic evidence: LA22.RT LA13.RT pol sequences LA31.RT LA14.RT LA17.RT LA29.RT LA26.RT LA10.RT Metzker et al., 2002 LA16.RT (PNAS 99:14292-14297) • Schmidt was convicted of attempted murder; currently serving term of 50 years of hard labor

• First use of phylogenetic analysis in U.S. criminal case

• Phylogenetics can be used to trace infections of human pathogens among individuals Outbreak clip? Prediction of future evolution of virus Phylogenetic prediction of the future of influenza:

Which current strains will lead to the epidemics of tomorrow?

years samples were taken

Bush et al., 1999 (Science 286:1921-1925) Hillis, 1999 (Science 286:1866-1867) Jurassic Park clip, cloning dinosaurs

American alligator domestic pigeon chicken archosaur zebra finch ancestor green anole human crab-eating macaque dog European rabbit cow house mouse Norway rat Chinese hamster Northern leopard frog common frog European toad giant toad African clawed frog tiger salamander goldfish common carp zebrafish Mexican characin sand goby soldierfish European eel conger eel little skate Japanese lamprey sea lamprey Chang et al., 2002 MBE 19:1483-1489

Star Trek clip, showing Tricorder

The Tree of Life You are here

Download wall poster from: http://www.zo.utexas.edu/faculty/antisense/DownloadfilesToL.html (see Science 300:1692-1697) The cotton in your You are here shirt came from here

What if, a billion years ago…

Download wall poster from: http://www.zo.utexas.edu/faculty/antisense/DownloadfilesToL.html (see Science 300:1692-1697) The cotton in your You are here shirt came from here

The E.coli in your gut is here

Download wall poster from: http://www.zo.utexas.edu/faculty/antisense/DownloadfilesToL.html (see Science 300:1692-1697) The cotton in your You are here shirt came from here

The E.coli The fungus in your gut on your foot is here is here Download wall poster from: http://www.zo.utexas.edu/faculty/antisense/DownloadfilesToL.html (see Science 300:1692-1697) To AmphibiaTree and beyond…

Download wall poster from: http://www.zo.utexas.edu/faculty/antisense/DownloadfilesToL.html (see Science 300:1692-1697) Described species

Species with sequences in GenBank Number of Described Species

10 (millions)

5 1.7 million species Number of described species described of Number described by 2007 163,572 in GenBank 0 on 5 July 2007 1750 1800 1850 1900 1950 2000 2025

Year Number of Described Species

20 Goal: Virtually all species known; a public online database for all species; 15 “complete” Encyclopedia of Life and Tree of Life

10 (millions)

5 Number of described species described of Number

0 1750 1800 1850 1900 1950 2000 2025

Year Number of Described Species

(millions) What needs to happen here? 5 Number of described species described of Number

0 1750 1800 1850 1900 1950 2000 2025

Year Number of Described Species

Species in 15 GenBank from phylogenomics studies?

(millions) What needs to happen here? 5 Number of described species described of Number

0 1750 1800 1850 1900 1950 2000 2025

Year Is a “Biocorder of Life” Possible?

Step one: Step two: Step three: DNA isolation and Rapid sequencing Placement of amplification of of amplified unknown within a series of genes the Tree of Life target genes

rRNA and other nuclear Information added to genes identify the global database unknown species of Life as a fungus

Go to Fungal Tree

Data, locality, life history, etc. Sample of target connected to the genes identify unknown fungus as Encyclopedia of Life; a chytrid: Batrachochytrium dendrobatidis connection to declines

pterophila neotenes latitans tridentifera

Blepsimolge nana

Notiomolge sosorum New sample

Paedomolge troglodytes Typhlomolge rathbuni

Eurycea robusta Septentriomolge naufragia tonkawae chisholmensis to other Eurycea to other Hemidactyliini Hillis et al., 2001 (Herpetologica 57:266-280), and unpublished data pterophila neotenes latitans tridentifera New sample Blepsimolge nana

Notiomolge sosorum

Paedomolge troglodytes Typhlomolge rathbuni

Blepsimolge nana

Notiomolge sosorum

Paedomolge troglodytes Typhlomolge rathbuni

Eurycea New sample robusta Septentriomolge naufragia tonkawae chisholmensis to other Eurycea to other Hemidactyliini Hillis et al., 2001 (Herpetologica 57:266-280), and unpublished data

Tree of Life (Phylogenomics) Approach

Advantages: • Can be automated; rapid rate increase • Cost per identification of each new species less than current methods, especially assuming development of automated and portable sequencing technology • Puts taxonomic knowledge in public databases, rather than just ephemeral human minds • Better uses the talents of taxonomic experts, who benefit from all the new data • Universal databases make taxonomy much more valuable and available to all biologists Dr. David Hillis David Hillis was born in Copenhagen, Denmark, but spent his formative years in tropical Africa and India. In this environment, Hillis learned a love of biology, entertaining himself by making collections of butterflies, amphibians, and reptiles. Hillis received his B.S. degree (with honors) from Baylor University in 1980, and M.A., M.Ph. and Ph.D. (all with honors) from The University of Kansas in 1983, 1984, and1985, respectively. After two years on the faculty at the University of Miami, he joined the Department of Zoology at UT Austin in 1987 and was awarded a prestigious National Science Foundation Presidential Young Investigator Award the same year. In1992, he was appointed to the Alfred W. Roark Centennial Professorship in Natural Sciences, and in 1998 became the first Director of the School of Biological Sciences at the University of Texas-Austin. In 1999, Hillis was one of 32 people chosen to receive a prestigious MacArthur Foundation fellowship, known informally as the "genius award”.

David Hillis’ research interests span much of biology, from development of statistical and computational methods for analyzing DNA sequences, to molecular studies of viral epidemiology, to studies of the diversity and phylogeny of life (particularly vertebrates), to the origin and behavior of unisexual organisms. He has published over 130 scholarly articles and two technical books, and has served as Editor or Associate Editor of a dozen scientific journals. He is an active member of many scholarly societies and national research panels, and has served as the President of the Society of Systematic Biologists. In the past decade, the 23 graduate students and 12 postdocs in his laboratory have produced an additional 120 independent scholarly articles.