1. PŘEDNÁŠKA MOL. BIOL.
2009-10
Nucleic acids
Historical view
Emil Paleček
Institute of Biophysics, Acad. Sci. CR v.v.i., 612 65 Brno
Czech Republic
G.J. Mendel
1866
The Road to DNA started in Brno
Chemická reaktivita a struktura nukleových
kyselin. Lokální struktury DNA stabilizované
superhelikálním vinutím; Interakce DNA a bílkovi
s povrchy; Interakce DNA-protein;
Elektrochemie nukleových kyselin a bílkovin;
Nádorové supresory, zejména protein p53; Agregace
bílkovin v neurodegenerativních chorobách (zejména
agregace -synucleinu v Parkinsonově chorobě)
31.36
52
264
8280
MENDEL
C K MATHEWS , K E van HOLDE, BIOCHEMISTRY, 1990
MIESCHER?
spíše do biochemie
Chemical nature and spatial organization Biological function
STRUCTURE
NUCLEIC ACIDS
F. MIESCHER, TÜBINGEN G. J. MENDEL, BRNO
1871 1866
Timeline of DNA
1865: Gregor Mendel discovers through breeding experiments with peas that traits are inherited based on specific laws
(later to be termed "Mendel's laws"). By mentioning Elements of Heredity he predicts DNA and genes (published 1866)
1866: Ernst Haeckel proposes that the nucleus contains the factors responsible for the transmission of hereditary traits.
1869: Friedrich Miescher isolates DNA/NUCLEIN for the first time.
1871: The first publications describing DNA (nuclein) by F Miescher, Felix Hoppe-Seyler, and P. Plosz are printed.
1882: Walther Flemming describes chromosomes and examines their behavior during cell division.
1884­1885: Oscar Hertwig, Albrecht von Kölliker, Eduard Strasburger, and August Weismann independently provide evidence
that the cell's nucleus contains the basis for inheritance.
1889: Richard Altmann renames nuclein to nucleic acid.
1900: Carl Correns, Hugo de Vries, and Erich von Tschermak rediscover Mendel's Laws.
1902: T Boveri and W Sutton postulate that the heredity units (called genes as of 1909) are located on chromosomes.
1902­1909: A Garrod proposes that genetic defects result in the loss of enzymes and hereditary metabolic diseases.
1909: Wilhelm Johannsen uses the word gene to describe units of heredity.
1910: T H Morgan uses fruit flies (Drosophila) as a model to study heredity and finds the first mutant with white eyes.
1913: Alfred Sturtevant and Thomas Hunt Morgan produce the first genetic linkage map (for the fruit fly Drosophila).
1928: Frederick Griffith postulates that a transforming principle permits properties from one type of bacteria (heatinactivated
virulent Streptococcus pneumoniae) to be transferred to another (live nonvirulent Streptococcus pneumoniae).
1929: P Levene identifies the building blocks of DNA, incl. four bases adenine (A), cytosine (C), guanine (G), thymine (T) .
1941: George Beadle and Edward Tatum demonstrate that every gene is responsible for the production of an enzyme.
1944: Oswald T. Avery, Colin MacLeod, and Maclyn McCarty demonstrate that Griffith's transforming principle is not a
protein, but rather DNA, suggesting that DNA may function as the genetic material
1949: Colette and Roger Vendrely and A Boivin discover that the nuclei of germ cells contain half the amount of DNA
that is found in somatic cells. This parallels the reduction in the number of chromosomes during gametogenesis and
provides further evidence for the fact that DNA is the genetic material.
1949­1950: Erwin Chargaff finds that the DNA base composition varies between species but determines that the bases
in DNA are always present in fixed ratios: the same number of A's as T's and the same number of C's as G's.
1952: Alfred Hershey and Martha Chase use viruses (bacteriophage T2) to confirm DNA as the genetic material by
demonstrating that during infection viral DNA enters the bacteria while the viral proteins do not and that this DNA can
be found in progeny virus particles.
1953: Rosalind Franklin and Maurice Wilkins use X-ray analyses to demonstrate that DNA has a regularly repeating
helical structure.
1953: James Watson and Francis Crick discover the molecular structure of DNA: a double helix in which A always pairs
with T, and C always with G.
1956: Arthur Kornberg discovers DNA polymerase, an enzyme that replicates DNA.
1957: Francis Crick proposes the central dogma (information in the DNA is translated into proteins through RNA) 1958:
Matthew Meselson and Franklin Stahl describe how DNA replicates (semiconservative replication).
1960-63: Julius Marmur and Paul Doty show separation of DNA strands and reformation of DNA double-helical
structure ­ DNA renaturation/hybridization
1961­1966: Robert W. Holley, Har Gobind Khorana, Heinrich Matthaei, Marshall W. Nirenberg, and colleagues crack the
genetic code.
1968­1970: Werner Arber, Hamilton Smith, and Daniel Nathans use restriction enzymes to cut DNA in specific places
for the first time.
1972: Paul Berg uses restriction enzymes to create the first piece of recombinant DNA.
1977: Frederick Sanger, Allan Maxam, and Walter Gilbert develop methods to sequence DNA.
1982: The first drug (human insulin), based on recombinant DNA, on the market.
1983: Kary Mullis invents PCR as a method for amplifying DNA in vitro.
1990: Sequencing of the human genome begins.
1995: First complete sequence of the genome of a free-living organism (the
bacterium Haemophilus influenzae) is published.
1996: The complete genome sequence of the first eukaryotic organism--the yeast
S. cerevisiae--is published.
1998: Complete genome sequence of the first multicellular organism--the
nematode worm Caenorhabditis elegans--is published.
1999: Sequence of the first human chromosome (22) is published.
2000: The complete sequences of the genomes of the fruit fly Drosophila and the
first plant--Arabidopsis--are published.
2001: The complete sequence of the human genome is published.
2002: The complete genome sequence of the first mammalian model organism--the
mouse--is published.
Darwin C. 1859: Book - On the Origin of Species by Means of Natural Selection
Mendel G. 1866
Miescher F. 1871
Charles Darwin - Important claims:
A. Universal Common Descent - Tree of Life - the first one-celled organism,
representing the root or trunk of the Tree, gradually developed and changed over
many generations into new and more complex forms, representing the branches
B. Natural Selection as a mechanism responsible for the branching pattern
Variations in living forms arise at random
Nature selects the adaptive ones
Adaptive organism survive and reproduce
Inherited adaptations may cause population changes
Darwin understand neither how genetic traits were passed to the progeny nor how
the variations arose. He is a founder of Evolution Biology
At present: - Natural Selection as a mechanism for relatively simple processes is
fully confirmed
- Universal Common Descent - Tree of Life and the role of natural selection in the
origin of species are questioned
papers
EVOLUČNÍ BIOLOGIE
- rychle se vyvíjející vědecká disciplina
vedle ní existuje IDEOLOGIE EVOLUCIONISMU
PODLE DARWINISTY M. RUSE NENÍ
BOJ EVOLUCIONISMU S KREACIONISMEM
BOJEM VĚDY S NÁBOŽENSTVÍM ALE
BOJEM NÁBOŽENSTVÍ S NÁBOŽENSTVÍM
M. Ruse, The Evolution-Creation Struggle
HARVARD UNIVERSITY PRESS , 2005
Horizontal gene transfer - cell conglomerate
instead of single cell ancestor
13
Thus we regard as regrettable
the conventional concatenation
of Darwin's name with evolution,
because other modalities must
also be considered
14
Sci. Amer. , Sept. 2009
JOHANN GREGOR MENDEL
* 1822 in Hynčice (Moravia, Austro-Hungarian Empire)
+ 1884 in Brno (buried at Central Cemetery in Brno)
In the 1950´s Mendelism declared to be a reactionary teaching (LYSENKO, LEPESHINSKAYA)
Mendel statue removed and its destruction ordered
Brno geneticist J. Kříženecký jailed
His pupil V. Orel forced to work manually in industry
1964 attempts to rehabilitate Mendel
Academicians B. Němec (biologist) and F. ŠORM (biochemist, President of the Czechoslovak Academy of Sciences)
backed by Soviet Academicians. Dealing between N. Khrushtchov, A. Novotný (President of Czechoslovakia), F. Šorm
and biologist J. Pospíšil (later the Party Secretary) resulted in the decision to organize an international conference
in 1968 (100 anniversary of publication of Mendel´s paper) in Brno (F. Šorm warned by Novotný that his attempts
may result in the end of his career if the action will get out of control). Beginning of Mendel´s Museum in Brno
A milestone not only in the approach of Party and State to Mendel but also a beginning of rehabilitation of
SCIENCE against the COMMUNIST IDEOLOGY
discovered through breeding experiments with peas that traits are inherited based
on specific laws (later to be termed "Mendel's laws"). By mentioning Elements of
Heredity he predicted DNA and genes (published 1866, lecture in Brno 1965)
Brno Augustinians 1860-62 Abbot C. Napp
Abbot G. Mendel
Teachers of Brno gymnasium (High School)
Mendel's Medal,
Moravian Museum, Brno
G J MENDEL, priest,
teacher, scientist and abbot
in BRNO
In 1956 Mendel`s Statue was ordered by the Regional Authorities to be destroyed.
The workers who were supposed to the job decided not to do it because they believed
that the statue was nice. Moreover it would be difficult to destroy it.
Before the Symposium the Director of the Institute of Biophysics prof. F. Hercik was entrusted by the Academy
to help with the organization of the Mendel International Meeting in Brno. To fulfill his duties he turned
to the City Authorities asking to move the Mendel`s Statue to the Abbey garden. As his request was ignored
he asked his graduate students J. Koudelka and B. Janík to move the Statue from the Abbey yard to the garden.
Both fellows were quite strong young men but they found the marble Statue too heavy.
THE STATUE STORY
In 1906 Dr. Hugo Iltis, the gymnasium professor in Brno organized an international
collection to build the Mendel`s Statue in Brno. Created by a French sculpturer
T. Charlemont the Statue was errected at the Mendel Square in 1910
After February 1948 Soviet ,,Lysenkism" (T. D. Lysenko 1896-1974) strongly
affected biology in Czechoslovakia. After Stalin death (1953) attempts were made
by soviet scientists (particularly by physists and chemists) to substitute Lysenko`s
,,materialistic biology" for normal science and by the end of 1950's plans were made to organize in Brno International Mendel
Memorial Symposium. In 1962 Lysenko`s work was criticized by the Soviet Academy but
still in September 1964 N.S. Khrushtchov raised objections against the Mendel Symposium in 1965 in Brno. During his visit
in Prague he dealt with the President A. Novotny who finally agreed with the meeting organization after the President of the
Academy F. Sorm personally guaranteed that the Symposium will not be politically misused. (F. Sorm was well informed about
the activities of the influential Soviet scientist to rehabilitate fully the genetics - Soon after his visit of this country N.S.
Khrushtchov was removed from his position).
Fig. 1. Friedrich Miescher and his mentors. (A) Friedrich Miescher (1844­1895) as a young man. (B) Wilhelm His (1831­1904), Miescher's uncle. His still is
famous for his work on the fate of cells and tissues during embryonic development and for his insights into neuroembryology. He, for example, discovered
neuroblasts and coined the term bdendriteQ (Finger, 1994; Shepherd, 1991). (C) Felix Hoppe-Seyler (1825­1895), one of the pioneers of physiological
chemistry (now biochemistry). Hoppe-Seyler performed seminal work on the properties of proteins, most notably hemoglobin (which he named), introduced
the term bproteidQ (which later became bproteinQ), and worked extensively on fermentation and oxidation processes as well as lipid metabolism (Perutz, 1995).
He was instrumental in founding Germany's first independent institute for physiological chemistry (in 1884) and in 1877 founded and edited the first journal of
biochemistry, the Zeitschrift fur Physiologische Chemie, which still exists today as Biological Chemistry. (D) Adolf Strecker (1822­1871), a leading figure in
chemistry in the mid-19th century and professor at the University of Tubingen from 1860 to 1870. Among other achievements, he was the first to synthesize
aamino acid (alanine from acetaldehyde via its condensation product with ammonia and hydrogen cyanide) in a reaction known today as Strecker synthesis
(Strecker, 1850). (E) Carl Ludwig (1816­1895), a protagonist in the field of physiology in the second half of the 19th century. His focus was the physiology of
the nervous system and its sensory organs. In 1869, he founded Leipzig's Physiological Institute.
F. Miescher W. His F. Hoppe-Seyler A. STRECKER
bmost simple and independent cell type,Q he hoped to
unravel the fundamental principles of the life of cells
(Miescher, 1869a).
the nucleiQ and he decided to examine the cells' nuclei more
closely--a part of the cell about which very little was
known at the time.
Fig. 2. Photograph of Felix Hoppe-Seyler's laboratory around 1879. Prior to becoming the chemical laboratory of Tqbingen University in 1823, this room was
Tqbingen castle's laundry. Here, Hoppe-Seyler had made ground-breaking discoveries regarding the properties of hemoglobin. This achievement was a
significant step for later investigations into the properties and functions of this and other proteins. Photography by Paul Sinner, Tqbingen.
Hoppe-Seyler's laboratory around 1879
ties, but by the presence of nuclein as this more closely
correlates with the nuclei's physiological function
(Miescher, 1870). However, neither Miescher nor his conhad
rested during his stay in Leipzig. However, owing to poor
working conditions, his progress initially was painfully slow
(Miescher, 1872b). In a letter to a friend he complained, bIn
Fig. 4. The laboratory in the former kitchen of the castle in Tqbingen as it was in 1879. It was in this room that Miescher had discovered DNA 10 years earlier.
The equipment and fixtures available to Miescher at the time would have been very similar, with a large distillation apparatus in the far corner of the room to
produce distilled water and several smaller utensils, such as glass alembics and a glass distillation column on the side board. Photography by Paul Sinner,
Tqbingen.
F. Miescher's laboratory
Text
Tübingen castle
A, in Miescher's time
B, at present
Before attempting the isolation of cells from the pus on surgical bandages, Miescher took great care to ensure that his
source material was fresh and not contaminated. He painstakingly examined it and discarded everything that showed signs
of decomposition, either in terms of smell, appearance under the microscope, or by having turned acidic. A great deal of the
material he could obtain did not meet these strict requirements (Miescher, 1871d). Those samples that did were
subsequently used to isolate leucocytes.
In a first step, Miescher separated the leucocytes from the bandaging material and the serum (Miescher, 1869a,
1871d). This separation posed a problem for Miescher. Solutions of NaCl or a variety of alkaline or alkaline earth salt
solutions used to wash the pus resulted in a "slimy swelling" of the cells, which was impossible to process further
(His, 1897b). (This "slimy swelling" of the cells was presumably due to high-molecular-weight DNA, which had been
extracted from cells that had been damaged.) Only when Miescher tried a dilute solution of sodium sulfate [a mixture
of one part cold saturated Glauber's salt (Na2SO4d 10 H2O) solution and nine parts water] to wash the bandages did he
manage to successfully isolate distinct leucocytes, which could be filtered out through a sheet to remove the cotton
fibers of the bandaging. Miescher subsequently let the washing solution stand for 1­2 h to allow the cells to sediment
and inspected the leucocytes microscopically to confirm that they did not show any signs of damage.
Having isolated the cells, Miescher next had to separate the nuclei from the cytoplasm. This had never been
achieved before and Miescher had to develop new protocols. He washed the cells by rinsing them several (6­10) times
with fresh solutions of diluted (1:1000) hydrochloric acid over a period of several weeks at "wintry temperatures"
(which were important to avoid degradation). This procedure removed most of the cells' bprotoplasm,Q leaving behind
the nuclei. The residue from this treatment consisted in part of isolated nuclei and of nuclei with only little fragments of
cytoplasm left attached. Miescher showed that these nuclei could no longer be stained yellow by iodine solutions, a
method commonly used at the time for detecting cytoplasm (Arnold, 1898; Kiernan, 2001).
He then vigorously shook the nuclei for an extended period of time with a mixture of water and ether. This caused
the lipids to dissolve in the ether while those nuclei, still attached to cytoplasm, collected at the water/ether interface.
By contrast, the clean nuclei without contaminating cytoplasm were retained in the water phase. Miescher filtered these
nuclei and examined them under a microscope. He noticed that in this way he could obtain completely pure nuclei
with a smooth contour, homogeneous content, sharply defined nucleolus, somewhat smaller in comparison to their
original volumes (Miescher, 1871d).
Miescher subsequently extracted the isolated nuclei with alkaline solutions. When adding highly diluted (1:100,000)
sodium carbonate to the nuclei, he noticed that they would swell significantly and become translucent. Miescher then
isolated a yellow solution of a substance from these nuclei. By adding acetic acid or hydrochloric acid in excess, he
could obtain an insoluble, flocculent precipitate (DNA). Miescher noted that he could dissolve the precipitate again by
adding alkaline solutions.
Although this protocol allowed Miescher for the first time to isolate nuclein in appreciable purity and quantities, it was
still too little and not pure enough for his subsequent analyses. He consequently improved on this protocol until he
established the protocol detailed in Box 2, which enabled him to purify sufficient amounts of nuclein for his first set of
experiments on its elementary composition.
Box 1
FIRST PROTOCOL
A key concern of Miescher's was to get rid of contaminating proteins, which would have
skewed his analyses of the novel substance. "I therefore turned to an agent that was
already being used in chemistry with albumin molecules on account of its strong proteindissolving
action, namely, pepsin solutions (Miescher, 1871d). Pepsin is a proteolytic
enzyme present in the stomach for digesting proteins. Miescher used it to separate the
DNA from the proteins of the cells' cytoplasm. He extracted the pepsin for his
experiments from pig stomachs by washing the stomachs with a mixture of 10 cc of
fuming hydrochloric acid and one liter of water and filtering the resulting solution until it
was clear. In contrast to his earlier protocol, Miescher first washed the pus cells
(leucocytes) three or four times with warm alcohol to remove lipids. He then let the
residual material digest with the pepsin solution between 18 and 24 h at 37­45 C. After
only a few hours, a fine gray powdery sediment of isolated nuclei separated from a yellow
liquid. Miescher continued the digestion process, changing the pepsin solution twice. After
this procedure, a precipitate of nuclei without any attached cytoplasm formed. He shook
the sediment several times with ether in order to remove the remaining lipids.
Afterwards, he filtered the nuclei and washed them with water until there was no longer
any trace of proteins. He described the nuclei isolated in this way as naked. The contours
were smooth in some cases or slightly eaten away in others (Miescher, 1871d). Miescher
washed the nuclei again several times with warm alcohol and noted that the nuclear mass
cleaned in this way exhibited the same chemical behavior as the nuclei isolated with
hydrochloric acid. Miescher subsequently extracted the isolated nuclei using the same
alkaline extraction protocol he had previously employed on the intact cells (see Box 1) and,
when adding an excess of acetic acid or hydrochloric acid to the solution, again obtained a
precipitate of nuclein.
M. SECOND PROTOCOL TO ISOLATE DNA
Fig. 5. Glass vial containing nuclein isolated from salmon sperm by
Friedrich Miescher while working at the University of Basel. The faded
label reads Nuclein aus Lachssperma, F. Miescher (Nuclein from salmon
sperm, F. Miescher). Possession of the Interfakult-res Institut fqr
Biochemie (Interfacultary Institute for Biochemistry), University of
Tubingen, Germany; photography by Alfons Renz, University of
Tubingen.
Fig. 6. This picture of Friedrich Miescher in his later years is the
frontispiece on the inside cover of the two volume collection of Miescher's
scientific publications, his letters, lecture manuscripts, and papers published
posthumously by Wilhelm His and others (His et al., 1897a,b).
(a) 1944: Oswald T. Avery, Colin MacLeod,
and Maclyn McCarty demonstrate that
Griffith's transforming principle is not a
protein, but rather DNA, suggesting that
DNA may function as the genetic material
(b) 1952: Alfred Hershey and Martha
Chase use viruses (bacteriophage T2) to
confirm DNA as the genetic material by
demonstrating that during infection viral
DNA enters the bacteria while the viral
proteins do not and that this DNA can be
found in progeny virus particles.
A, B and left-handed Z-DNA
as we know them now
How did we arrive to them ?
30
21st Anniversary:
The DNA Double Helix
Comes of Age
31
1953
A paragraph dealing with nucleic acids
from a text book of Organic Chemistry (in Czech) is shown.
Briefly, it says nucleic acids (NA`s) form complexes with
proteins which are the building blocks of plant and animal
viruses and of cell nucleus. Total hydrolysis of NA`s proceeds
according to the following scheme:
alkaline hydrolysis enzym. digestion
Polynucleotide mononucleotide uracil or purine bases
Considering that uracil and adenine were discovered in 1885 and G in 1844
while C in 1894 and T in 1900, our lectures on NA`s were up-todate in 1885
but not in 1894
In courses of Marxism-Leninism (obligatory to all students)
we were tought that G. Mendel was a burgeous reactionary pseudoscientist.
Interestingly there was not a single chemist among us who believed it.
To my surprise there were some biologists who took this nonsenses seriously
Chargaff`s Rules
Tetranucleotide hypothesis originated in 1906: DNA is a "statistical tetranucleotide".
During the 1950´s E. Chargaff showed a number of DNAs, which differ in their base content.
Chargaff´s rules: 1. 6-amino residues = 6-keto-residues; in another expression A+C = G+T;
2. py = pu; C+T = G+A 3. A/T = G/C = 1 (consequence of combining equations 1 and 2)
Watson and Crick (1953) proposed their famous double-helical structure of B-form of DNA on the
ground of Chargaff´s rules
* X-ray diffraction of DNA fibers obtained by Maurice Wilkins and Rosalind Franklin
* Construction of molecular models
This structure consists of two antiparallel helical strands. One turn contains 10 residues in every
strand, the distance between bases is 3.4 A, the bases are almost perpendicular to the axis, the
phosphate group is 9 A from the axis. Bases are specifically paired through hydrogen bonds ­ AT and
GC. The strands are complementary ­ hydrogen bonds between two strands, the bases are inside the
structure. Difference from -helix in polypeptides. Further forms A and C (besides B): dependence
on humidity. The differences are principally in the tilt of bases and in the number of residues per turn,
strands are commonly antiparallel, bases are stacked and base pairs located in one plane. It seems that
the B-form is the prevalent one in solution as well as in cells and viral particles.
Crick, Watson and Wilkins: Nobel Prize 1962
"The structure is produced like a rabbit out of a hat, with no indication as to how we arrived at it"
F. Crick, NATURE 248(1974) 766- on the occasion of the 21st anniversary of the discovery
(commenting their first paper in NATURE). What experimental evidence was available to W+C in 1953?
Text
DNA is a polyanionic biomacromolecule with bases in its interior and sugar-phosphate
backbone on the surface. At neutral pH it carries one negative charge per nucleotide. Below
pH 5 and and above pH 9 ionization of bases become important
36
Parameters of DNA structures
A B Z
DNA structures from X-ray crystal analysis
DNA double helix is polymorphic
depending on the nucleotide sequence
37
LEFT-HANDED Z-DNA
alternating pu-py
CRUCIFORM
inverted repeat
CURVATURE
4-6 A's in phase with
the helix turns
SINGLE-STRANDED region
AT-rich
Text
TRIPLEX structure
homopu.
homopy
HAIRPIN
SUPERCOIL
Negative SUPERCOILING stabilizes
local DNA structures
Physical methods such as NMR and X-ray analysis indispensable in the research of
linear DNA structures are of limited use in studies of local structures stabilized
by supercoiling
Problems of life origin
What was first - DNA, RNA or protein?
Well-known Oxford zoologist Professor Richard Dawkins (who declares himself
to be passionate fighter for the truth) writes in his book River out of Eden:
"At the beginning of Life Explosion there was no mind, no creativity, no intent,
there was only chemistry"
Let us try to summarize what chemistry it was
40
PROBLEMS OF LIFE ORIGINS
The Miller-Urey experiment attempted to recreate the chemical conditions of the
primitive Earth in the laboratory, and synthesized some of the building blocks of life
but geologists showed that prebiotic atmosphere
was not strongly reducing and not oxygen-free,
differring from that expected by Miller and Urey
S. Miller and H. Urey subjected
mixture of methane, ammonia and
hydrogen to an electric discharge
and led the product into water ...
Cytosine synthesis would not be possible
even strongly in reducing
prebiotic atmosphere.
Similar problems arise with the abiotic
synthesis of nucleotides
Abiotic synthesis of a complicated
molecule such as RNA is highly improbable
43
44
NOBEL lareate Christian de Duve has called for "a rejection of improbablities so
incomensurably high that they only can be called miracles, phenomena that fall outside
the scope of scientific inquiry". DNA, RNA and PROTEINS must then be set aside as
participants in the origin of life.
45
46
Peptide Nucleic Acid (PNA)
47
Sci. Amer. Dec. 2008
48
Or did life come from
another world?
The hypothesis of F. Crick is
discussed in November issue of
Scientific American 2005.
It is concluded that microorganism
could have survived a journey from
Mars to Earth
Recent finding of glycine in the
comet tail might be considered as
support for this alternative
RNA First
Metabolism first (2007)
PNA First (2008)
RNA First (again/2009)
Panspermia again and again
Panspermia
The actual nature of
the first organism and
the exact
circumstances of the
origin of life may be
forever lost for
science.
But research can at
least help to
understand what is
possible
Sci.Amer., September 2009
+
+
Native DNA
melting melting
quick cooling quick cooling
melted DNA
slow cooling
renaturation
denatured DNA RENATURED DNA
Temperature
premelting
C
D
A, B C D
A260
A B
DNA DENATURATION and RENATURATION/HYBRIDIZATION
J. Marmur and P. Doty
Microbiologist, biochemist and molecular biologist
Julius Marmur ­ dicovered renaturation of DNA
22 March, 1926 Bialystok (Poland) ­ 20 May, 1996 New York, NY
Oswald Avery 1944 - DNA is a genetic material
(Rockefeller Institute, New York, NY)
Rollin D. Hotchkiss
Julius Marmur
1993
Nature 248(1974) 766
Francis Crick 21 years after invention of
the DNA double helix structure
about the discovery of DNA
renaturation
KEY CONCEPTS
* Scientists long assumed
that any DNA mutation
that does not change
the final protein
encoded by a gene is
effectively "silent".
* Mysterious exceptions
to the rule, in which
silent changes seemed to
be exerting a powerful
effect on proteins, have
revealed that such
mutations can affect
health through a
variety of mechanisms.
* Understanding the
subtler dynamics of how
genes work and evolve
may reveal further
insights into causes and
cures for disease.
MUFFLED MESSAGE
A synonymous mutation was found to affect pain sensitivity by changing the amount of
an important enzyme that cells produced. The difference results from alteration in the
shape of mRNA that can influence how easily ribosomes are able to unpackage and read
the strand. The folded shape is caused by base-pairing of the mRNA´s nucleotides;
therefore, a synonymous mutation can alter the way nucleotides match up.