The Search for DNA

1
The Search for DNA
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Biology in the Late 1800s

• As the 19th century came to a close, tremendous
  leaps were made in the biological sciences.
• What caused the observable phenomenon of life and
  heredity was no longer being explained as the
  secrets of the divine.
• Instead, ideas such as natural selection,
  discrete factors, genotypes, phenotypes,
  chromosomes and DNA were revealed.

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Darwin and Mendel

• Neither Darwin nor Mendel were microbiologists.
• They observed the nature that was visible to
  their eyes and deduced from that what it must all
  mean at the invisible level.
• Incredibly, they never collaborated even though
  each held the piece of the puzzle the other was
  missing.

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Gemmules

• When Darwin published his paper on The Origin of
  Species by Natural Selection in 1859 he still
  held to the Aristotelian idea that heredity was
  passed by seeds from the limbs, organs etc. that
  were carried in the blood to the gametes.
• Darwin held that these seeds were called gemmules

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Discrete Factors

• Mendel, who lived at the same time, recognized
  that the heredity factors were the invisible
  genotypes of organisms that led to the visible
  phenotypes.
• Since discrete factors were in both plants and
  animals, it did not make sense that they were
  passed by blood.

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Mendel

• However, Mendel only studied the phenotypes of
  organisms.
• He used the phenotypes to deduce genotypes but he
  did not actually see them.
• He left the microbiology to others just as Darwin
  had done.
• The question remained If blood did not carry
  heredity, what did?

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Molecular Theory

• Other scientists were exploring a molecular
  theory of heredity.
• The work of Leeuwenhoek, the father of microscopy
  and William Harvey, the father of modern
  medicine, showed that blood probably did not
  carry the genetic factors.
• Instead, a different theorya molecular theory of
  heredity was emerging.

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Chromosomes

• Chromosomes were first observed in the nucleus of
  plant cells by Swiss botanist Karl Wilhelm von
  Nägeli in 1842, and independently Belgian
  scientist Edouard Van Beneden
• Walther Flemming realized the importance of
  chromosomes when he observed mitosis, seeing
  cells divide for the first time.

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Flemming

• Flemming called the material that made up the
  chromosomes chromatin.
• Chromatin was made up of proteins and other
  unidentified nuclear material.
• Could it be that the key to heredity was a
  molecule?

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Miescher

• DNA was first discovered as a major chemical of
  the nucleus by Swiss scientist Friedrich
  Miescher.
• Meischer isolated what he termed "nuclein while
  working at a local hospital in Tübingen, Germany.

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Nuclein (DNA)

• Miescher would study white blood cells by
  collecting pus-soaked bandages.
• He learned that the only source for nuclein was
  chromosomes,
• This supported the "chemical heredity theory,"
  which claims that our basic biological
  information is passed from generation to
  generation and is stored in chemical substances
  in our cells. Animation
• http//www.dnaftb.org/dnaftb/15/concept/index.html
  

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Mendel Rediscovered

• At the turn of the century, scientists
  rediscovered Mendels work which had been ignored
  for 30 years.
• Wilhelm Johansen rediscovered Mendels work.
• He renamed Mendels discrete factors, calling
  them genes.

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Thomas Hunt Morgan

• The work of Thomas Hunt Morgan in the early
  1900s (remember the white eyed fruit flies)
  showed that genes were located on specific
  locations on chromosomes.
• By now it was clear that heredity was passed by a
  molecule that was located on genes in the
  nucleus.
• However, it was originally thought that proteins
  were the molecules that transferred hereditary
  information, not DNA.

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DNA

• Although DNA was known to be a very large
  molecule, scientists knew it only had four
  nitrogen bases
• Adenine
• Thymine
• Guanine
• Cytosine
• DNA seemed to simple to explain the vast
  diversity of life.

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Role of DNA

• DNA did not appear to have a major role in the
  cell.
• Proteins on the other hand were important for
  cell structure and function.
• Proteins seemed to be complicated enough to
  explain the diversity of life.
• Instead of only four bases for DNA, proteins used
  20 different amino acids to form their complex
  structure.
• DNA Problem
• http//www.dnaftb.org/dnaftb/15/concept/index.html
  

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Transformation Chemical

• In the 1920s experiments showed that an alive,
  harmless strain of bacteria can cause an
  infection when mixed with a harmful strain of
  bacteria that had been killed.
• Apparently a chemical in the dead bacteria
  transformed the harmless bacteria into infectious
  bacteria.

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Oswald Avery

• The transforming principle appeared to be a gene.
• A team of scientists led by Oswald Avery came up
  with an ingenious method to identify the
  transforming gene.
• They extracted a pure strain of the transforming
  principle and treated it with different digesting
  enzymes.

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DNA Stopped the Change

• Protein digesting enzymes did not stop the
  transformation but DNA digesting enzymes did stop
  the transformation.
• Problem
• http//www.dnaftb.org/dnaftb/17/concept/index.html
  

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Alfred Hershey and Edward Tatum

• Still, scientists were skeptical about DNA being
  the genetic material.
• The final clue that established DNA as the
  genetic material was the discovery of viruses and
  their relationship with bacteria to form what are
  called bacteriophages.

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Bacteriophages

• Because bacteria have a single cell, the viral
  DNA will transform the entire organism when it
  causes the infection.
• The studies showed that when viruses infected
  bacteria it was not proteins that got transferred
  from the virus to the bacteria but instead DNA.
• It was also found that when bacteria conjugated,
  the virus was passed from one bacteria to
  another.

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The Structure of DNA

• By the 1950s, several facts were already known
  about DNA.
• DNA is composed of nucleotides composed of
• A deoxyribose sugar
• A phosphate group

• 4 Nitrogenous Bases
• Adenine
• Guanine
• Cytosine
• Thymine

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The Structure of DNA

• It was also known that the phosphates and sugars
  of adjacent nucleotides link to form a long
  polymer (a long molecule made up of several
  monomers).
• Also, the ratios of A to T and G to C are
  constant in all living things.
• The question was how did it all fit together?

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The Race Was On

• The race was between three teams.
• Two of the teams were in Britain.
• Team one was Maurice Wilkins and Rosalind
  Franklin from Kings College in England.
• Team two was James Watson and Frances Crick at
  Cambridge University in England.
• The third team was run by the esteemed chemist
  Linus Pauling at UCLA.

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Linus Pauling

• Pauling had discovered a technique called X-ray
  crystallography that allowed scientists to see
  the 3-dimensional shape of proteins.
• He found that many proteins had an alpha helical
  shape.
• Pauling would go on to win two Nobel prizes, one
  in chemistry and also the Nobel Peace Prize.
• However, when Pauling got it wrong when he
  published a paper showing a triple helix, the
  prize went to Watson and Crick in Englandsort
  of.

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Espionage

• Rosalind Franklin and Maurice Wilkins were trying
  to identify the structure by studying X-ray
  diffractions of the DNA molecule.
• Watson and Crick studied the work of everyone
  perhaps cheating along the way.
• Watson has been accused of stealing Franklin's
  X-ray work and using that knowledge to solve the
  pieces of the puzzle they could not quite get on
  their own.

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The Solution

• Watson and Crick found that alternating
  deoxyribose and phosphate molecules form the
  twisted upright legs of the DNA ladder in a
  double alpha helix (right handed).
• The rungs of the ladder are formed by
  complementary pairs of nitrogen bases.
• The reason why A is proportional to T and G is
  proportional to C is because A always pairs with
  T and G always pairs with C.
• Animation and Problem
• http//www.dnaftb.org/dnaftb/19/concept/index.html

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Citations

• http//www.dnaftb.org
• http//www.pbs.org/wgbh/nova/genome/heredity.html
• http//www.pbs.org/wnet/dna/episode1/index.html
• http//www.wjc.ku.dk/wilhelm/