DNA in Hollywood Fact, Fiction and Future

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DNA in HollywoodFact, Fiction and Future
by Dr. David Hillis Hot Science - Cool Talks
Volume 49
Produced by and for the Hot Science - Cool Talks
Outreach Lecture Series of the Environmental
Science Institute. We request that the use of
any of these materials include an acknowledgement
of Dr. David Hillis and the Hot Science - Cool
Talks Outreach Lecture Series of the
Environmental Science Institute of the University
of Texas at Austin. We hope you find these
materials educational and enjoyable.
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DNA in HollywoodFact, Fiction, and Future

• David M. Hillis
• Section of Integrative Biology
• Center for Computational Biology
• The University of Texas at Austin

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Phylogenetic analysis can be used to trace viral
infections through a human population

• Origins of HIV, SARS and other viruses
  transmitted between animals and humans
• Global virus diversity for vaccine trials
• Epidemiological studies
• Identification of new diseases
• Forensic uses

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Phylogeny Papers, 1981-2006 (with phylogeny or
phylogenetic in title or abstract)
9000 8000 7000 6000 5000 4000 3000 2000 1000 0
Number of papers per year
1980
1985
1990
1995
2000
2005
Year of publication
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PhylogenyEvolutionary relationships among
lineages, such as genes, individuals,
populations, species, etc.
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PhylogenyEvolutionary relationships among
lineages, such as genes, individuals,
populations, species, etc.
One lineage splits into two
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PhylogenyEvolutionary relationships among
lineages, such as genes, individuals,
populations, species, etc.
There are now two HIV lineages
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PhylogenyEvolutionary relationships among
lineages, such as genes, individuals,
populations, species, etc.
Some lineages become extinct
x
Lineages continue to diversify through time
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PhylogenyEvolutionary relationships among
lineages, such as genes, individuals,
populations, species, etc.
x
The relationships among lineages produce a
phylogenetic tree
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PhylogenyEvolutionary relationships among
lineages, such as genes, individuals,
populations, species, etc.
If samples are taken at this point in time
x
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PhylogenyEvolutionary relationships among
lineages, such as genes, individuals,
populations, species, etc.
then the reconstructed phylogenetic tree will
look like this
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Phylogeny How is evolutionary history
reconstructed?
x
Each of these tick marks represents a new
mutation in the genome of the respective HIV
lineage
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Phylogeny How is evolutionary history
reconstructed?
1 2 3 4 5 6
Lineages 1 and 2 will share these mutations
x
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Phylogeny How is evolutionary history
reconstructed?
1 2 3 4 5 6
x
Lineages 1, 2, 3, and 4 will share these mutations
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Phylogeny How is evolutionary history
reconstructed?
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
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How do we know phylogenetic analysis
works? Experimental evolution to test
phylogenetic methods
ancestral nodes
internode distance -400 generations (40 serial
transfers)
T7 (wild type)
Hillis et al., 1992 (Science 255589-592)3
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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
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At the transmission event, the HIV in the
recipient represents a small subset of the HIV
present in the source
Time 2 The transmission event
To recipient
HIV sequence sampled from source
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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
x
Immune system has eliminated the lineage
Time of transmission
x
x
x
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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
Time of transmission
x
x
x
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• 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

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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 2861921-1925)
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Hillis, 1999 (Science 2861866-1867)
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Chang et al., 2002 MBE 191483-1489
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The Tree of Life
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You are here
(see Science 3001692-1697)
Download wall poster from http//www.zo.utexas.ed
u/faculty/antisense/DownloadfilesToL.html
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The cotton in your shirt came from here
You are here
(see Science 3001692-1697)
Download wall poster from http//www.zo.utexas.ed
u/faculty/antisense/DownloadfilesToL.html
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The cotton in your shirt came from here
You are here
What if, a billion years ago
(see Science 3001692-1697)
Download wall poster from http//www.zo.utexas.ed
u/faculty/antisense/DownloadfilesToL.html
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The cotton in your shirt came from here
You are here
The E.coli in your gut is here
(see Science 3001692-1697)
Download wall poster from http//www.zo.utexas.ed
u/faculty/antisense/DownloadfilesToL.html
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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
(see Science 3001692-1697)
Download wall poster from http//www.zo.utexas.ed
u/faculty/antisense/DownloadfilesToL.html
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To AmphibiaTree and beyond
(see Science 3001692-1697)
Download wall poster from http//www.zo.utexas.ed
u/faculty/antisense/DownloadfilesToL.html
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Described species
Species with sequences in GenBank
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Number of Described Species
20
15
Number of described species (millions)
10
5
1.7 million species described by 2007
163,572 in GenBank on 5 July 2007
0
1750
1800
1850
1900
1950
2000
2025
Year
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Number of Described Species
20
Goal Virtually all species known a public
online database for all species complete
Encyclopedia of Life and Tree of Life
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Number of described species (millions)
10
5
0
1750
1800
1850
1900
1950
2000
2025
Year
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Number of Described Species
20
15
Number of described species (millions)
10
What needs to
happen here?
5
0
1750
1800
1850
1900
1950
2000
2025
Year
40
Number of Described Species
20
Species in GenBank from phylogenomics studies?
15
Number of described species (millions)
10
What needs to
happen here?
5
0
1750
1800
1850
1900
1950
2000
2025
Year
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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
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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
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pterophila
neotenes
latitans
tridentifera
nana
Blepsimolge
sosorum
Notiomolge
Paedomolge
troglodytes
Typhlomolge
rathbuni
New sample
Eurycea
robusta
naufragia
Septentriomolge
tonkawae
chisholmensis
to other Eurycea
to other Hemidactyliini
Hillis et al., 2001 (Herpetologica 57266-280),
and unpublished data
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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