1. DNA in Hollywood: Fact, Fiction, and Future
Hot Science - Cool Talk # 49
DNA in Hollywood: Fact, Fiction, and Future
Dr. David Hillis
September 14, 2007
Produced by and for Hot Science - Cool Talks by the Environmental Science Institute. We request that the use of these materials include an acknowledgement of the presenter and Hot Science - Cool Talks by the Environmental Science Institute at UT Austin. We hope you find these materials educational and enjoyable.

2. DNA in Hollywood Fact, Fiction, and Future
David M. Hillis
Section of Integrative Biology &
Center for Computational Biology
The University of Texas at Austin

3. CSI clip

4. 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

5. (with “phylogeny” or “phylogenetic” in title or abstract)
Phylogeny Papers,
(with “phylogeny” or “phylogenetic” in title or abstract)
9000
8000
7000
6000
5000
4000
3000
2000
1000
Number of papers per year
1980
1985
1990
1995
2000
2005
Year of publication

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

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

8. There are now two HIV lineages
Phylogeny Evolutionary relationships among lineages, such as genes, individuals, populations, species, etc.
Time
There are now two HIV lineages

9. Phylogeny Evolutionary relationships among lineages, such as genes, individuals, populations, species, etc.
Time
Some lineages
become extinct x
Lineages continue
to diversify
through time

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

11. Phylogeny Evolutionary relationships among lineages, such as genes, individuals, populations, species, etc.
If samples are
taken at this
point in time…
Time x
…then the reconstructed
phylogenetic tree will look like this

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

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

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

15. Phylogeny How is evolutionary history reconstructed?
Time
A model of HIV evolution
is used to account for multiple changes to the same sites on a genome, different rates of changes among sites, and other details of HIV evolution

16. How do we know phylogenetic
analysis works?
Experimental evolution to test phylogenetic methods 1 2 3 4 5 6 7 8 9
ancestral
nodes
internode distance =
-400 generations
(40 serial transfers)
T7 (wild type)
Hillis et al., 1992 (Science 255: )3

17. 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

18. 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

19. 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
Immune system has terminated the lineage x x x x x
Time of
transmission

20. Time 4: Further after transmission event
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 from recipient
HIV sequence sampled from source x x x x x x x x x x x x x x x
Time of
transmission

21. Phylogenetic evidence:a t i e n t . a
New sequences added p a t i e n t . b v i c t i m . a v i c t i m . b p a t i e n t . c p a t i e n t . d
Transmission from
patient to victim p a t i e n t . e p a t i e n t . f p a t i e n t . g L A 8 . R T L A 2 . R T L A 5 . R T L A 3 2 . R T L A 6 . R T L A 1 2 . R T L A 1 8 . R T L A 3 . R T L A 2 7 . R T L A 2 3 . R T L A 7 . R T L A 2 8 . R T L A 2 5 . R T L A 4 . R T L A 2 1 . R T
Phylogenetic evidence:
pol sequences L A 2 4 . R T L A 2 2 . R T L A 1 3 . R T L A 3 1 . R T L A 1 4 . R T L A 1 7 . R T L A 2 9 . R T L A 2 6 . R T L A 1 . R T
Metzker et al., 2002
(PNAS 99: ) L A 1 6 . R T

22. 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

23. Outbreak clip? Prediction of future evolution of virus

24. 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: )

25. Hillis, 1999
(Science 286: )

26. Jurassic Park clip, cloning dinosaurs

28. archosaur ancestor American alligator domestic pigeon chicken
zebra finch
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:

30. Star Trek clip, showing Tricorder

32. The Tree of Life
This tree of life has 3,000 species. That’s less than 0.2% of the species currently on the planet, which in turn are less than 1% of the species that have lived on this planet over the last 540 million years.

33. You are here
Download wall poster from:
(see Science 300: )

34. The cotton in your shirt came from here You are here
Download wall poster from:
(see Science 300: )

35. What if, a billion years ago…
The cotton in your
shirt came from here
You are here
What if, a billion years ago…
Download wall poster from:
(see Science 300: )

36. The cotton in your shirt came from here You are here The E.coli
in your gut
is here
Download wall poster from:
(see Science 300: )

37. The cotton in your shirt came from here You are here The E.coli
in your gut
is here
The fungus
on your foot
is here
Download wall poster from:
(see Science 300: )

38. To AmphibiaTree and beyond…
Download wall poster from:
(see Science 300: )

39. Species with sequences
Described species
Species with sequences
in GenBank

40. Number of Described Species Number of described species20 15
Number of described species
(millions) 10 5
1.7 million species
described by 2007
163,572 in GenBank
on 5 July 2007
1750
1800
1850
1900
1950
2000
2025
Year

41. Number of Described Species Number of described species20
Goal: Virtually all species known; a public online database for all species; “complete” Encyclopedia of Life and Tree of Life 15
Number of described species
(millions) 10 5
1750
1800
1850
1900
1950
2000
2025
Year

42. Number of Described Species Number of described species20 15
Number of described species
(millions) 10
What needs to
happen here? 5
1750
1800
1850
1900
1950
2000
2025
Year

43. Number of Described Species Number of described species20
Species in
GenBank from
phylogenomics
studies? 15
Number of described species
(millions) 10
What needs to
happen here? 5
1750
1800
1850
1900
1950
2000
2025
Year

44. Is a “Biocorder of Life” Possible?
Step one:
DNA isolation and
amplification of
a series of
target genes
Step two:
Rapid sequencing
of amplified
genes
Step three:
Placement of
unknown within
the Tree of Life

46. Information added to
the global database
of Life
rRNA and other nuclear
genes identify
unknown species
as a fungus
Go to
Fungal Tree
Data, locality,
life history, etc.
connected to the
Encyclopedia of Life;
connection to declines
Sample of target
genes identify unknown fungus as
a chytrid: Batrachochytrium dendrobatidis

50. to other Hemidactyliini
pterophila
neotenes
latitans
tridentifera
nana
Blepsimolge
Notiomolge
sosorum
New sample
Paedomolge
troglodytes
Typhlomolge
rathbuni
Eurycea
robusta
naufragia
Septentriomolge
tonkawae
chisholmensis
to other Eurycea
to other Hemidactyliini
Hillis et al., 2001 (Herpetologica 57: ), and unpublished data

51. to other Hemidactyliini
pterophila
neotenes
latitans
tridentifera
New sample
nana
Blepsimolge
Notiomolge
sosorum
Paedomolge
troglodytes
Typhlomolge
rathbuni
Eurycea
robusta
naufragia
Septentriomolge
tonkawae
chisholmensis
to other Eurycea
to other Hemidactyliini
Hillis et al., 2001 (Herpetologica 57: ), and unpublished data

52. to other Hemidactyliini
pterophila
neotenes
latitans
tridentifera
nana
Blepsimolge
Notiomolge
sosorum
Paedomolge
troglodytes
Typhlomolge
rathbuni
New sample
Eurycea
robusta
naufragia
Septentriomolge
tonkawae
chisholmensis
to other Eurycea
to other Hemidactyliini
Hillis et al., 2001 (Herpetologica 57: ), and unpublished data

54. 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

55. 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.