Discovery of DNA Structure and Function
DNA was first identified in the late 1860s by Friedrich Miescher.
Other scientists--notably, Phoebus Levene and Erwin Chargaff - found additional details about the
DNA molecule, including its chemical components and the ways in which they joined with one
another.
Miescher Discovers DNA
1869 Miescher found "nuclein" inside the nuclei of human white blood cells.
(The term "nuclein" was later changed to "nucleic acid" and eventually to "deoxyribonucleic acid,"
or "DNA.")
Levene Investigates the Structure of DNA
Levene discovered
the order of the three major components of a single nucleotide (phosphate-sugar-base);
the carbohydrate component of RNA (ribose);
the carbohydrate component of DNA (deoxyribose); and
the way RNA and DNA molecules are put together (polynucleotide).
1919 - nucleic acids were composed of a series of nucleotides, and that each nucleotide was in turn
composed of just one of four nitrogen-containing bases, a sugar molecule [either a ribose (in the
case of RNA) or a deoxyribose (in the case of DNA)], and a phosphate group.
Later Scientists found
The order of nucleotides along a stretch of DNA (or RNA) is, in fact, highly variable. There are two
basic categories of nitrogenous bases: the purines (adenine [A] and guanine [G]), each with two
fused rings, and the pyrimidines (cytosine [C], thymine [T], and uracil [U]), each with a single ring.
RNA contains only A, G, C, and U (no T), whereas DNA contains only A, G, C, and T (no U) .
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Chargaff Formulates His "Rules"
Chargaff had read the about the work of Oswald Avery and his colleagues which showed that
hereditary units, or genes, are composed of DNA.
Developed a new paper chromatography method for separating and identifying small amounts of
organic material
1950 - the nucleotide composition of DNA varies among species, the same nucleotides do not
repeat in the same order.
Almost all DNA maintains certain properties.
The amount of adenine (A) is usually similar to the amount of thymine (T), and the amount of
guanine (G) usually approximates the amount of cytosine (C).
The total amount of purines (A + G) = the total amount of pyrimidines (C + T). (Chargaff's rule.)
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Rosalind Franklin
The X-ray crystallograph pattern of DNA obtained by Rosalind
Franklin and Raymond Gosling in 1952.
It was clearer than the other X-ray patterns because water was
included in the DNA sample.
The distinctive "X" in this X-ray photo is the telltale pattern of a
helix.
Because the X-ray pattern is so regular, the dimensions of the
helix must also be consistent.
For example, the diameter of the helix stays the same.
The closer the spots, the larger
The horizontal bats correspond to
Yje vertical distance between the
measure of one turn, 34
the distance.
helical turns.
bars is a
Angstroms.
The distance
from the
middle of the X-ray patter to the top is measurable
at 3.4 angstroms. This is the distance between two
stacked base pairs.
There is 10 nucleotides per helical repeat.
The helix’s rise angle can be calculated
angle the X makes with the horizontal axis.
Franklin deduced that the phosphates were
outside.
Franklin and Maurice Wilkins calculated the
dimensions of the DNA structure.
Watson and Crick Propose the Double
from the
on the
basic
Helix
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Watson and Crick used the previous information.
Also advances in model building, or the assembly of possible three-dimensional structures based
upon known molecular distances and bond angles, a technique developed by biochemist Linus
Pauling.
They were mistaken for a while by an wrong understanding of how the different elements in
thymine and guanine (specifically, the carbon, nitrogen, hydrogen, and oxygen rings) were shaped.
The suggestion of scientist Jerry Donohue caused them to make new cardboard cutouts of the two
bases.
The different atomic configuration made a difference.
The complementary bases now fit together perfectly (i.e., A with T and C with G), with each pair
held together by hydrogen bonds, and the structure also reflected Chargaff's rule.
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The four major features are:




DNA is a double-stranded helix, with the two strands connected by hydrogen bonds. A bases
are always paired with Ts, and Cs are always paired with Gs.
Most DNA double helices are right-handed. Only one type of DNA, called Z-DNA, is lefthanded.
The DNA double helix is anti-parallel, which means that the 5' end of one strand is paired
with the 3' end of its complementary strand (and vice versa). Nucleotides are linked to each
other by their phosphate groups, which bind the 3' end of one sugar to the 5' end of the
next sugar.
The DNA base pairs are connected via hydrogen bonding, and the outer edges of the
nitrogen-containing bases are exposed and available for potential hydrogen bonding as well.
These hydrogen bonds provide easy access to the DNA for other molecules, including the
proteins that are important in the replication and expression of DNA.
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Figure 4 : Base pairing in DNA is complementary.
More findings
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Three different conformations of the DNA double helix have been found.
The most common conformation in most living cells is known as B-DNA.
A-DNA, a shorter and wider form that has been found in dehydrated samples of DNA and rarely
under normal physiological circumstances.
Z-DNA, a left-handed confirmation, only occasionally exists in response to certain types of biological
activity (discovered in 1979)
Certain proteins bind very strongly to Z-DNA, suggesting that Z-DNA plays an important biological
role in protection against viral disease.
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Figure 5 : DNA can assume several different secondary structures.
These structures depend on the base sequence of the DNA and the conditions under which it is
placed.
Control of Development
Material from http://evolution.berkeley.edu/evolibrary/article/side_0_0/complexity_01
The adult is composed of a lot of very different parts made of different cells.
every cell carries the same genetic instructions.
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How does it "know" what to do?
Certain genes control where and when other genes are expressed
Regulatory genes control when and where other genes get turned on.
Regulatory genes can start a "chain reaction" of effects, turning on and off other genes, whose
products affect other genes, whose products in their turn affect other genes, and so on.
A single regulatory gene can control the construction of a body part as complex as an eye.
Different cells have different genes expressed
Different segments of the developing fly embryo express different genes.
Chemical signals also influence the fate of cells
Chemical signals from the environment and from other cells can affect which genes are
turned on in a particular cell.
Eg. In the developing vertebrate eye, chemical signals from the retina probably cause
adjacent cells to become lens cells instead of some other type of cells.
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