How we got here
Where we’re going
What is life?
Shiloh Pitt/Jolie
http://www.sawf.org
Allposters.com
• Where do organisms come from?
Pasteur 1865
Darwin 1859
• How do organisms propagate?
Mendel 1866
Watson & Crick 1953
1865
Louis Pasteur refutes the
doctrine of spontaneous generation.
Louis Pasteur
1822 - 1895
Copyright © 1995-2004 Lucid Interactive
http://www.lucidcafe.com/
Copyright,© 1996, 2001 David V. Cohn, Ph.D., University of Louisville
http://www.foundersofscience.net/interest1.htm#Spontaneous%20Generation
• Where do organisms come from?
Pasteur 1865
Darwin 1859
• How do organisms propagate?
Mendel 1866
Watson & Crick 1953
Genesis I
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.
1831 - 1836
Darwin sails on the voyage of
the HMS Beagle.
Darwin’s finches
en.wikipedia.org
© Copyright 2000-2004 AboutDarwin.com
http://www.aboutdarwin.com/
taken from: http://www.rit.edu/~rhrsbi/GalapagosPages/DarwinFinch.html
by Dr. Robert Rothman, Rochester Institute of Technology
Erasmus Darwin
Down House
On the Tendency of Varieties to Depart Indefinitely from the
Original Type
Alfred Russel Wallace
1823 - 1913
© 1998, 2000-2003 by Charles H. Smith
http://www.wku.edu/~smithch/index1.htm
1858
Alfred Russel Wallace sends Darwin a ms. entitled:
1859
Darwin publishes On the Origin of Species.
Charles Darwin
1809 -1882
© Copyright 2000-2004 AboutDarwin.com
http://www.aboutdarwin.com/pictures/Darwin/Darwin.html
• Where do organisms come from?
• How do organisms propagate?
Like begets like
©MMIV, CBS Broadcasting Inc. (Photo: AP)
Reuters
~ 6000 BCE
Domestication of crops and animals
Copyright 1996 by InterCity Oz, Inc.
http://www.touregypt.net/magazine/mag07012001/magf5.htm
~ 400
BCE
The Greeks devise
the theory of pangenesis:
“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).”
1875
http://www.aboutdarwin.com/pictures/Darwin/Darwin.html
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
Darwin proposes the idea of
"gemmules" as a mechanism
of inheritance.
© 2000-2004 AboutDarwin.com
1889
Francis 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/
• Where do organisms come from?
Pasteur 1865
Darwin 1859
• How do organisms propagate?
Mendel 1866
Watson & Crick 1953
1866
Gregor Mendel publishes his findings on heredity
in peas in Versuche über Pflanzen Hybriden.
Gregor Mendel
1822-1884
Mendel Museum of Genetics, Brno, Czech Republic
http://www.mendel-museum.org/eng/1online/garden.htm
1900 Mendel’s work discovered
from: J. Felsenstein, University of Washington
1902
William Bateson coins the term
GENETICS
1915 The Mechanism of Mendelian Heredity
T. H. Mogan
A. H. Sturtevant
C.B. Bridges
H.J. Muller
Chromosomes are the vehicles of heredity
Genes are on chromosomes
Genes can change (mutate)
What are genes made of ???
• Where do organisms come from?
Pasteur 1865
Darwin 1859
• How do organisms propagate?
Mendel 1866
Watson & Crick 1953
1831
Robert Brown reports the widespread occurrence of nuclei in cells.
Ernst Heinrich Haeckel
1834-1919
©Copyright Contexo.info 2002
http://www.contexo.info/DNA_Basics/Nucleus.htm
1864
Ernst Haeckel hypothesizes that the
nucleus of a cell transmits its
hereditary information.
http://www.nceas.ucsb.edu/~alroy/lefa/Haeckel.html
1871
Miescher isolates nucleic acid
from nuclei of white blood cells.
Friedrich Miescher
1844-1895
© 2000 - 2003 The Center for the Advancement of Genomics (TCAG)
http://www.laskerfoundation.org/news/gnn/timeline/1869a.html
1943
• The nucleus transmits genetic information
(Haeckel)
• Chromosomes carry genetic information
AND are in the nucleus (Morgan et al.)
• The nucleus contains nucleic acid (Miescher)
1944
Schrödinger asks “what is life?”
Erwin Schrödinger
1887 - 1961
http://www-groups.dcs.st-and.ac.uk/~history/PictDisplay/Schrodinger.html
http://www.amazon.com
“……living
matter, while not eluding the ‘laws of physics’ as established up to date,
is likely to involve ‘other laws of physics’ hitherto unknown…...”
“…. I
do not expect that any detailed information on this
question is likely to come ……… in the near future.”
1944
Avery, McCarty and MacLeod show that
DNA is the hereditary chemical!
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.
smooth colonies
(kill mice)
rough colonies
(don’t kill mice)
Smooth cell extract
“transforming principle”
Copyright ©2004 John W. Kimball
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/Avery.html
1950
• The nucleus transmits genetic information
• Chromosomes carry genetic information
AND are in the nucleus
• The nucleus contains DNA
• DNA carries genetic information
We have
found the
secret of life!
Feb. 28, 1953
April 25, 1953
1962
Jim Watson
1928 -
Watson, Crick and Wilkins
win the Nobel Prize
Francis Crick
1916 - 2004
Maurice Wilkins
1916 - 2004
© Nature News Service / Macmillan Magazines Ltd 2003
http://www.nature.com/nsu/dna50/index.html#names
Rosalind Franklin
1920 - 1958
1950-~1970 Unravelling of how the cell decodes DNA
The Central
Dogma of Molecular Biology
DNA
RNA
Protein
• Where do organisms come from?
• How do organisms propagate?
What is life?
Shiloh Pitt/Jolie
http://www.sawf.org
DNA Chemistry!
1980 - ~2000 Identify all the parts
DNA
RNA
Protein
1977
Fred Sanger & Wally Gilbert
http://www.nobel.se/chemistry/laureates/1980/
Describe methods for determining
the sequence of nucleotides in DNA
CTGGAAGAGGTATGTGCGCCGTTTCTGTTATCACAGTGTGCAATCCCATTACCGCATATCAGTTATAACAATAGTAATGGTAGCGCCATT
AAAAATATTGTCGGTTCTGCAACTATCGCCCAATACCCTACTCTTCCGGAGGAAAATGTCAACAATATCAGTGTTAAATATGTTTCTCCT
GGCTCAGTAGGGCCTTCACCTGTGCCATTGAAATCAGGAGCAAGTTTCAGTGATCTAGTCAAGCTGTTATCTAACCGTCCACCCTCTCGT
AACTCTCCAGTGACAATACCAAGAAGCACACCTTCGCATCGCTCAGTCACGCCTTTTCTAGGGCAACAGCAACAGCTGCAATCATTAGTG
CCACTGACCCCGTCTGCTTTGTTTGGTGGCGCCAATTTTAATCAAAGTGGGAATATTGCTGATAGCTCATTGTCCTTCACTTTCACTAAC
AGTAGCAACGGTCCGAACCTCATAACAACTCAAACAAATTCTCAAGCGCTTTCACAACCAATTGCCTCCTCTAACGTTCATGATAACTTC
ATGAATAATGAAATCACGGCTAGTAAAATTGATGATGGTAATAATTCAAAACCACTGTCACCTGGTTGGACGGACCAAACTGCGTATAAC
GCGTTTGGAATCACTACAGGGATGTTTAATACCACTACAATGGATGATGTATATAACTATCTATTCGATGATGAAGATACCCCACCAAAC
CCAAAAAAAATATGTGCAAAAAAATGCTTGATGATTTGTAATGAGATTGAGGAGGTTTCGAGACAGGCACCAAAGTTTTTACAAATGGAT
1980
Fred Sanger & Wally Gilbert
awarded the Nobel Prize in Chemistry
Feb. 15, 2001
Not so many genes!
6000 14,000 19,000
20,500
How we got here
How we got here
Where we’re going
2001 - ??? Determine
function!
6000 14,000 19,000
20,500
How many yeast workers?
attendees at yeast meeting:
fraction of yeast workers attending meeting:
~ 850
~1/7
(perhaps a large sampling error…….)
total scientists working on yeast:
~6000
Persons / gene:
~1
first authors, 2003-2007:
9447
Lourdes Peña-Castillo & Tim Hughes
Genetics 176:7
# of
genes “known”
Progress finding yeast protein function
4679 proteins “known”
Oct. 14, 2003
time
Yeast Protein Database www.proteome.com
6000 proteins “known”
April 1, 2007  11.4 days
# of
genes “known”
“Solving” yeast
time
Yeast Protein Database www.proteome.com
• Only 38 genes with no information available
• Only 566 lack any annotations in any of
the three major branches of Gene Ontology
biological process
molecular function
cellular component
As of March 20, 2007
Saccharomyces Genome Database
(Mike Cherry et al., Stanford)
Lourdes Peña-Castillo and Tim Hughes (2007) Genetics 176:7
YPD http://biobase-international.com/
There are still
1253 uncharacterized yeast genes
—21% of all genes—
As of March 20, 2007
Saccharomyces Genome Database
(Mike Cherry et al., Stanford)
Lourdes Peña-Castillo and Tim Hughes (2007) Genetics 176:7
Progress finding yeast protein function
7000
6000
6000
verified genesgenes
“verified”
1253 uncharacterized genes
5000
4000
3000
April 1, 2007
2000
1000
0
Apr-05
Jan-08
Apr
‘05
Oct-10
Jan
‘08
Jul-13
Oct
‘10
Apr-16
Date
Date
Lourdes Peña-Castillo and Tim Hughes (2007) Genetics 176:7
Dec-18
Apr ‘16
Sep-21
Dec
‘18
Jun-24
Sep
‘21
Mar-27
“Solving” yeast
6000 proteins “known”
April 1, 2020  63 days
“verified” genes
6000
April 1, 2007
Apr ‘05
Jan ‘08
Oct ‘10
Lourdes Peña-Castillo and Tim Hughes (2007) Genetics 176:7
Date
Apr ‘16
Dec ‘18
Sep ‘21
X
gene 1
gene 2
gene 3
gene 1
X
gene 2
Each gene
“knocked out”
gene 3
X
gene 5998 gene 5999 gene 6000
promoter
Each gene
overexpressed
gene 1
promoter
gene 2
promoter gene
6000
protein 1
various epitopes
tnx activation domain
fluorescent proteins
protein 2
Each protein
tagged with
many things
various epitopes
tnx activation domain
fluorescent proteins
protein 6000
various epitopes
tnx activation domain
fluorescent proteins
Protein localization images
Nucleus
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
Mike Tyers & Matthias Mann Nature 422: 196 2003
Genomics = Resources
>
Golden Age of
Molecular Biology
The “post-genomic era”
• comprehensive understanding of organisms
• diagnosing and predicting human disease
• repairing human disease
The Encyclopedia of Life
6000 14,000 19,000
20,500