how we got here where we’re going. shiloh pitt/jolie what is life? allposters.com
TRANSCRIPT
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How we got here
Where we’re going
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Shiloh Pitt/Jolie http://www.sawf.org
What is life?
Allposters.com
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Mendel 1866Watson & Crick 1953
• Where do organisms come from?
• How do organisms propagate?
Pasteur 1865Darwin 1859
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Louis Pasteur1822 - 1895
Copyright © 1995-2004 Lucid Interactivehttp://www.lucidcafe.com/
Copyright,© 1996, 2001 David V. Cohn, Ph.D., University of Louisvillehttp://www.foundersofscience.net/interest1.htm#Spontaneous%20Generation
Louis Pasteur refutes the doctrine of spontaneous generation.1865
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Pasteur 1865Darwin 1859
Mendel 1866Watson & Crick 1953
• Where do organisms come from?
• How do organisms propagate?
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Then God said, "Let the earth put forth vegetation: plants yielding seed, and fruit trees of every kind on earth that bear fruit with the seed in it.” The earth brought forth vegetation: plants yielding seed of every kind, and trees of every kind bearing fruit. And God saw that it was good.
And God said, "Let the waters bring forth swarms of living creatures…..So God created the great sea monsters and every living creature that moves... And God saw that it was good.
Genesis I
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Darwin sails on the voyage of the HMS Beagle.
© Copyright 2000-2004 AboutDarwin.comhttp://www.aboutdarwin.com/
1831 - 1836Darwin’s finches
taken from: http://www.rit.edu/~rhrsbi/GalapagosPages/DarwinFinch.htmlby Dr. Robert Rothman, Rochester Institute of Technology Erasmus Darwin
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Down House
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Alfred Russel Wallace1823 - 1913
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1858Alfred Russel Wallace sends Darwin a ms. entitled:
On the Tendency of Varieties to Depart Indefinitely from the Original Type
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Charles Darwin1809 -1882
© Copyright 2000-2004 AboutDarwin.comhttp://www.aboutdarwin.com/pictures/Darwin/Darwin.html
Darwin publishes On the Origin of Species.1859
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• Where do organisms come from?
• How do organisms propagate?
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©MMIV, CBS Broadcasting Inc. (Photo: AP)
Like begets like
Reuters
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Copyright 1996 by InterCity Oz, Inc.http://www.touregypt.net/magazine/mag07012001/magf5.htm
~ 6000 BCE Domestication of crops and animals
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Darwin proposes the idea of "gemmules" as a mechanism of inheritance.
1875
© 2000-2004 AboutDarwin.com
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The Greeks devise the theory of pangenesis:
~ 400 BCE
“From every part of the body are produced particles which Mix with the bodily fluids … and are carried by them to the testicles.... The offspring resembles its parent because the particles of the semen come from every part of the body. (Hippocrates, VII, 471-75).”
from: The Dictionary of the History of Ideas© 2003 the Gale Group
http://etext.lib.virginia.edu/cgi-local/DHI/dhi.cgi?id=dv2-69
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1889Francis Galton disproves pangenesis: transfusing blood from black rabbits into white rabbits fails to yield black offspring.Sir Francis Galton
1822-1911
http://www.mugu.com/galton/
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Pasteur 1865Darwin 1859
Mendel 1866Watson & Crick 1953
• Where do organisms come from?
• How do organisms propagate?
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Gregor Mendel publishes his findings on heredity in peas in Versuche über Pflanzen Hybriden. 1866
Mendel Museum of Genetics, Brno, Czech Republichttp://www.mendel-museum.org/eng/1online/garden.htm
Gregor Mendel1822-1884
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Mendel’s work discovered1900
from: J. Felsenstein, University of Washington
William Bateson coins the term
GENETICS1902
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A. H. Sturtevant C.B. Bridges H.J. Muller
1915 The Mechanism of Mendelian Heredity
Chromosomes are the vehicles of heredity
Genes are on chromosomes
Genes can change (mutate)
T. H. Mogan
What are genes made of ???
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Pasteur 1865Darwin 1859
Mendel 1866Watson & Crick 1953
• Where do organisms come from?
• How do organisms propagate?
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Ernst Haeckel hypothesizes that the nucleus of a cell transmits its hereditary information.
Ernst Heinrich Haeckel 1834-1919
http://www.nceas.ucsb.edu/~alroy/lefa/Haeckel.html
1864
Robert Brown reports the widespread occurrence of nuclei in cells. 1831
©Copyright Contexo.info 2002http://www.contexo.info/DNA_Basics/Nucleus.htm
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Miescher isolates nucleic acid from nuclei of white blood cells.
© 2000 - 2003 The Center for the Advancement of Genomics (TCAG)http://www.laskerfoundation.org/news/gnn/timeline/1869a.html
Friedrich Miescher 1844-1895
1871
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• Chromosomes carry genetic information
AND are in the nucleus (Morgan et al.)
• The nucleus contains nucleic acid (Miescher)
1943• The nucleus transmits genetic information
(Haeckel)
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http://www-groups.dcs.st-and.ac.uk/~history/PictDisplay/Schrodinger.html
Erwin Schrödinger1887 - 1961
http://www.amazon.com
1944 Schrödinger asks “what is life?”
“…. I do not expect that any detailed information on this question is likely to come ……… in the near future.”
“……living matter, while not eluding the ‘laws of physics’ as established up to date,
is likely to involve ‘other laws of physics’ hitherto unknown…...”
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Avery, McCarty and MacLeod show that
DNA is the hereditary chemical!1944
Smooth cell extract
“transforming principle”
Copyright ©2004 John W. Kimballhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/Avery.html
smooth colonies(kill mice)
rough colonies(don’t kill mice)
STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING
TRANSFORMATION OF PNEUMOCOCCAL TYPES : INDUCTION OF TRANSFORMATION
BY A DESOXYRIBONUCLEIC ACID FRACTION ISOLATED FROM PNEUMOCOCCUS TYPE III.
Avery OT, Macleod CM, McCarty M.J Exp Med. 1944 79:137-58.
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• The nucleus transmits genetic information
• Chromosomes carry genetic information
AND are in the nucleus
• The nucleus contains DNA
• DNA carries genetic information
1950
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We have found the
secret of life!
Feb. 28, 1953
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April 25, 1953
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1962 Watson, Crick and Wilkins
win the Nobel Prize
Maurice Wilkins1916 - 2004
Rosalind Franklin1920 - 1958
Francis Crick1916 - 2004
Jim Watson1928 -
© Nature News Service / Macmillan Magazines Ltd 2003http://www.nature.com/nsu/dna50/index.html#names
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DNA
RNA
Protein
The Central Dogma of Molecular Biology
1950-~1970 Unravelling of how the cell decodes DNA
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• Where do organisms come from?
• How do organisms propagate?
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Shiloh Pitt/Jolie http://www.sawf.org
What is life?
DNA Chemistry!
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DNA
RNA
Protein
1980 - ~2000 Identify all the parts
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1980 Fred Sanger & Wally Gilbert awarded the Nobel Prize in Chemistry
1977 Fred Sanger & Wally Gilbert
Describe methods for determiningthe sequence of nucleotides in DNA
http://www.nobel.se/chemistry/laureates/1980/
CTGGAAGAGGTATGTGCGCCGTTTCTGTTATCACAGTGTGCAATCCCATTACCGCATATCAGTTATAACAATAGTAATGGTAGCGCCATTAAAAATATTGTCGGTTCTGCAACTATCGCCCAATACCCTACTCTTCCGGAGGAAAATGTCAACAATATCAGTGTTAAATATGTTTCTCCTGGCTCAGTAGGGCCTTCACCTGTGCCATTGAAATCAGGAGCAAGTTTCAGTGATCTAGTCAAGCTGTTATCTAACCGTCCACCCTCTCGTAACTCTCCAGTGACAATACCAAGAAGCACACCTTCGCATCGCTCAGTCACGCCTTTTCTAGGGCAACAGCAACAGCTGCAATCATTAGTGCCACTGACCCCGTCTGCTTTGTTTGGTGGCGCCAATTTTAATCAAAGTGGGAATATTGCTGATAGCTCATTGTCCTTCACTTTCACTAACAGTAGCAACGGTCCGAACCTCATAACAACTCAAACAAATTCTCAAGCGCTTTCACAACCAATTGCCTCCTCTAACGTTCATGATAACTTCATGAATAATGAAATCACGGCTAGTAAAATTGATGATGGTAATAATTCAAAACCACTGTCACCTGGTTGGACGGACCAAACTGCGTATAACGCGTTTGGAATCACTACAGGGATGTTTAATACCACTACAATGGATGATGTATATAACTATCTATTCGATGATGAAGATACCCCACCAAACCCAAAAAAAATATGTGCAAAAAAATGCTTGATGATTTGTAATGAGATTGAGGAGGTTTCGAGACAGGCACCAAAGTTTTTACAAATGGAT
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Feb. 15, 2001
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6000 19,00014,000
Not so many genes!
20,500
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How we got here
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How we got here
Where we’re going
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6000 19,00014,000
Determine function!
20,500
2001 - ???
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total scientists working on yeast: ~6000
How many yeast workers?
~ 1Persons / gene:
~ 1 / 7(perhaps a large sampling error…….)
fraction of yeast workers attending meeting:
~ 850attendees at yeast meeting:
Lourdes Peña-Castillo & Tim HughesGenetics 176:7
first authors, 2003-2007: 9447
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# of
gen
es “k
now
n”
time
Progress finding yeast protein function
Yeast Protein Database www.proteome.com
4679 proteins “known” Oct. 14, 2003
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# of
gen
es “k
now
n”
timeYeast Protein Database www.proteome.com
6000 proteins “known” April 1, 2007
“Solving” yeast 11.4 days
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• Only 38 genes with no information available
• Only 566 lack any annotations in any of the three major branches of Gene Ontology
biological processmolecular functioncellular component
Saccharomyces Genome Database (Mike Cherry et al., Stanford)
As of March 20, 2007
Lourdes Peña-Castillo and Tim Hughes (2007) Genetics 176:7
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YPD http://biobase-international.com/
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There are still 1253 uncharacterized yeast genes
—21% of all genes—
Saccharomyces Genome Database (Mike Cherry et al., Stanford)
As of March 20, 2007
Lourdes Peña-Castillo and Tim Hughes (2007) Genetics 176:7
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April 1, 2007
6000
1253 uncharacterized genes
Date
Progress finding yeast protein function“v
erif
ied”
gen
es
Lourdes Peña-Castillo and Tim Hughes (2007) Genetics 176:7
Jan ‘08Apr ‘05 Oct ‘10 Apr ‘16 Dec ‘18 Sep ‘21
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April 1, 2007
6000
Date
“ver
ifie
d” g
enes
Lourdes Peña-Castillo and Tim Hughes (2007) Genetics 176:7
Jan ‘08Apr ‘05 Oct ‘10 Apr ‘16 Dec ‘18 Sep ‘21
6000 proteins “known” 63 days April 1, 2020
“Solving” yeast
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gene 1 gene 2 gene 3
gene 5998 gene 5999 gene 6000
X
X
Each gene “knocked out”
gene 1 gene 2 gene 3X
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gene 1Each gene
overexpressedpromoter
gene 2promoter
gene 6000promoter
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protein 1various epitopes
tnx activation domainfluorescent proteins
protein 2various epitopes
tnx activation domainfluorescent proteins
protein 6000various epitopes
tnx activation domainfluorescent proteins
Each proteintagged withmany things
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Protein localization imagesNucleus Nuclear periphery Endoplasmic reticulum
Bud neck Mitochondrion Lipid particle
Huh et al. et Weissman et O'Shea (2003) Global analysis of protein localization in budding yeast. Nature 425:686-91
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Mike Tyers & Matthias Mann Nature 422: 196 2003
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Genomics = Resources
Golden Age of Molecular Biology
>
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The “post-genomic era”• comprehensive understanding of organisms
• diagnosing and predicting human disease
• repairing human disease
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6000 19,00014,000
The Encyclopedia of Life
20,500