Atlas de Genética

Atlas de Genética


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A chain. The A and the B chains are
connected by two disulfide bridges joining the
cysteines in position 7 and position 20 of the A
chain to those of positions 7 and 19, respec-
tively, of the B chain. The A chain contains a di-
sulfide bridge between positions 6 and 11. The
positions of the cysteines reflect the spatial ar-
rangements of the amino acids, called the sec-
ondary structure.
C. Secondary structural units,
the \u3b1 helix and the " sheet
Two basic units of global proteins are \u3b1 helix
formation (\u3b1 helix) and a flat sheet (" pleated
sheet). Panel C shows a schematic drawing of a
unit of one\u3b1 helix between two "-sheets, called
a "\u3b1" unit (Figure redrawn from Stryer, 1995).
D. Tertiary structure of insulin
All functional proteins assume a well-defined
three-dimensional structure. This structure is
defined by the sequence of amino acids and
their physicochemical properties. Tertiary
structure is defined by the spatial arrangement
of amino acid residues that are far apart in the
linear sequence. The quaternary structure is the
folding of the protein resulting in a specific
three-dimensional spatial arrangement of the
subunits and the nature of their contacts. The
correct quaternary structure ensures proper
function. (Figure from Koolman & Röhm, 1996).
References
Koolman, J., Röhm, K.-H.: Color Atlas of Bio-
chemistry. Thieme, Stuttgart\u2013New York,
1996.
Stryer, L.: Biochemistry, 4th ed. W.H. Freeman &
Co., New York, 1995.
Fundamentals
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All rights reserved. Usage subject to terms and conditions of license.
33Proteins
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All rights reserved. Usage subject to terms and conditions of license.
34
DNA as Carrier of Genetic
Information
Although DNA was discovered in 1869 by Frie-
drich Miescher as a new, acidic, phosphorus-
containing substance made up of very large
molecules that he named \u201cnuclein\u201d, its biologi-
cal rolewas not recognized. In 1889 Richard Alt-
mann introduced the term \u201cnucleic acid\u201d. By
1900 the purine and pyrimidine bases were
known. Twenty years later, the two kinds of nu-
cleic acids, RNA and DNA, were distinguished.
An incidental but precise observation (1928)
and relevant investigations (1944) indicated
that DNA could be the carrier of genetic infor-
mation.
A. The observation of Griffith
In 1928 the English microbiologist Fred Griffith
made a remarkable observation. While investi-
gating various strains of Pneumococcus, he de-
termined that mice injected with strain S
(smooth) died (1). On the other hand, animals
injected with strain R (rough) lived (2). When
he inactivated the lethal S strain by heat, there
were no sequelae, and the animal survived (3).
Surprisingly, a mixture of the nonlethal R strain
and the heat-inactivated S strain had a lethal ef-
fect like the S strain (4). And he found normal
living pneumococci of the S strain in the ani-
mal\u2019s blood. Apparently, cells of the R strain
were changed into cells of the S strain (trans-
formed). For a time, this surprising result could
not be explained and was met with skepticism.
Its relevance for genetics was not apparent.
B. The transforming principle is DNA
Griffith\u2019s findings formed the basis for inves-
tigations by Avery, MacLeod, and McCarty
(1944). Avery and co-workers at the Rockefeller
Institute in New York elucidated the chemical
basis of the transforming principle. From cul-
tures of an S strain (1) they produced an extract
of lysed cells (cell-free extract) (2). After all its
proteins, lipids, and polysaccharides had been
removed, the extract still retained the ability to
transform pneumococci of the R strain to
pneumococci of the S strain (transforming prin-
ciple) (3).
With further studies, Avery and co-workers de-
termined that this was attributed to the DNA
alone. Thus, the DNA must contain the corre-
sponding genetic information. This explained
Griffith\u2019s observation. Heat inactivation had left
the DNA of the bacterial chromosomes intact.
The section of the chromosome with the gene
responsible for capsule formation (S gene)
could be released from the destroyed S cells and
be taken up by some R cells in subsequent cul-
tures. After the S gene was incorporated into its
DNA, an R cellwas transformed into an S cell (4).
Page 90 shows how bacteria can take up foreign
DNA so that some of their genetic attributeswill
be altered correspondingly.
C. Genetic information is transmitted
by DNA alone
The final evidence that DNA, and no other
molecule, transmits genetic information was
provided by Hershey and Chase in 1952. They
labeled the capsular protein of bacteriophages
(see p. 88) with radioactive sulfur (35S) and the
DNA with radioactive phosphorus (32P). When
bacteria were infected with the labeled bacte-
riophage, only 32P (DNA) entered the cells, and
not the 35S (capsular protein). The subsequent
formation of new, complete phage particles in
the cell proved that DNA was the exclusive car-
rier of the genetic information needed to form
new phage particles, including their capsular
protein. Next, the structure and function of DNA
needed to be clarified. The genes of all cells and
some viruses consist of DNA, a long-chained
threadlike molecule.
References
Avery, O.T., MacLeod, C.M., McCarty, M.: Studies
on the chemical nature of the substance in-
ducing transformation of pneumococcal
types. J. Exp. Med. 79:137\u2013158, 1944.
Griffith, F., The significance of pneumoccocal
types. J. Hyg. 27:113\u2013159, 1928.
Hershey, A.D., Chase, M.: Independent func-
tions of viral protein and nucleic acid in
growth of bacteriophage. J. Gen. Physiol.
36:39\u201356, 1952.
Judson, M.F.: The Eighth Day of Creation.
Makers of the Revolution in Biology. Ex-
panded Edition. Cold Spring Harbor Labora-
tory Press, New York, 1996.
McCarty, M.: The Transforming Principle. Dis-
covering that Genes are made of DNA. W.W.
Norton & Co., New York\u2013London, 1985.
Fundamentals
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All rights reserved. Usage subject to terms and conditions of license.
35DNA as Carrier of Genetic Information
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36
DNA and Its Components
The information for the development and
specific functions of cells and tissues is stored in
the genes. A gene is a portion of the genetic in-
formation, definable according to structure and
function. Genes lie on chromosomes in the nu-
clei of cells. They consist of a complex long-
chained molecule, deoxyribonucleic acid
(DNA). In the following, the constituents of the
DNA molecule will be presented. DNA is a nu-
cleic acid. Its chemical components are nu-
cleotide bases, a sugar (deoxyribose), and
phosphate groups. They determine the three-
dimensional structure of DNA, from which it
derives its functional consequence.
A. Nucleotide bases
The nucleotide bases in DNA are heterocyclic
molecules derived from either pyrimidine or
purine. Five bases occur in the two types of nu-
cleic acids, DNA and RNA. The purine bases are
adenine (A) and guanine (G). The pyrimidine
bases are thymine (T) and cytosine (C) in DNA.
In RNA, uracil (U) is present instead of thymine.
The nucleotide bases are part of a subunit of
DNA, the nucleotide. This consists of one of the
four nucleotide bases, a sugar (deoxyribose),
and a phosphate group. The nitrogen atom in
position 9 of a purine or in position 1 of a py-
rimidine is bound to the carbon in position 1 of
the sugar (N-glycosidic bond).
Ribonucleic acid (RNA) differs from DNA in two
respects: it contains ribose instead of deoxyri-
bose (unlike the latter, ribose has a hydroxyl
group on the position 2 carbon atom) and uracil
(U) instead of thymine. Uracil does not have a
methyl group at position C5.
B. Nucleotide