Heredity and Development Second Edition (1972) / Chapter Skim
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8 DNA - Structure and Function
8 DNA - Structure and Function
Pages 167-208
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From page 167... ...
Many chemical studies were made on calf thymus glands, which were obtained from local slaughter houses. When nucleic acid of the thymus gland was hydrolyzed, it was found to consist of only a few components: adenine, guanine, cytosine, thymine, deoxyribose (a sugar)
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From page 168... ...
Here was a problem of clear and obvious importance. It was vigorously investi 8–1 The hydrolysis products of DNA and RNA.
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From page 169... ...
In 1944 it was established that DNA is the transforming substance in Diplococcus; evidence obtained in 1952 suggested strongly that the entire genetic information of the T2 phage is DNA. With leads of this sort, it is not surprising that many
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From page 170... ...
Bridges advanced the hypothesis of non-disjunction on the basis of genetic data and tested his hypothesis by a study of the chromosomes of his experimental material. The hypothesis that pieces of chromosomes may become inverted was suggested by genetic data and confirmed by a study of the salivary gland chromosomes.
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From page 171... ...
3. The available data on the X-ray diffraction patterns suggested to Watson and Crick that the DNA molecule consists of two long fibers twisted around one another to form a double helix (like double spiral staircases, one for ascent and one for descent)
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From page 172... ...
5. Each fiber of the double helix consists of phosphate and deoxyribose units alternating with one another: phosphate-deoxyribose-phosphate deoxyribose, and so on.
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From page 173... ...
These bonds would form if the bases were opposite one another in the positions suggested by the model. Further evidence for this specific pairing came from data on the relative sizes of the bases and of the diameter of the DNA molecule.
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From page 174... ...
, and phosphoric acid (P)
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From page 175... ...
Now our model for deoxyribonucleic acid is, in effect, a pair of templates, each of which is complementary to the other. We imagine that prior to duplication the hydrogen bonds [between the bases opposite to one another in the two strands]
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From page 176... ...
In this diagram the upper portion of the DNA double helix has not started to replicate. In the central section the strands have separated
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From page 177... ...
During the next decade an ever-increasing amount of chemical and genetic data suggested that the hypothesis was indeed correct. In 1962 Watson and Crick shared the Nobel Prize with Maurice Wilkins, the physicist from Cambridge University who had supplied much of the X-ray data indicating that DNA is a double helix with a uniform diameter of 20 Ångstrom units.
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From page 178... ...
The four polypeptides of the molecule are linked together and folded in a compact and specific manner to give the hemoglobin molecule a globular shape. Since the most obvious feature of sickle cell anemia is the abnormality of the red blood cells, it is reasonable to suppose that the hemoglobin of these cells might also be abnormal.
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From page 179... ...
Thus, if the three types of hemoglobin differed in their charges, they could be separated, and thereby shown to be different. This analytical device shows that normal hemoglobin, which we can call hemoglobin A, differs from sickle cell hemoglobin, which we can call hemoglobin S (Fig.
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From page 180... ...
Since these amino acids are always in the same places in the hemoglobin molecule, the hemoglobin will always be broken down in the same way. When the hemoglobin molecule is broken with trypsin, the result is 28 kinds of smaller molecules, averaging about ten amino acids each.
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From page 181... ...
. 8–6 The hydrolysis products of normal hemoglobin and sickle cell hemoglobin.
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From page 182... ...
In individuals with sickle cell anemia, an abnormal hemoglobin, hemoglobin S, is made under the influence of a mutant allele. When formed by the mutant allele, the β chain of the hemoglobin differs from the normal in a single amino acid substitution: valine rather than glutamic acid is the sixth amino acid from the end of the long chain of 146 amino acids.
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From page 183... ...
Since the bases are situated largely in DNA or RNA, a peak absorption at 260 mµ indicates the occurrence of nucleic acids. This method will not distinguish between DNA and RNA; it measures total DNA plus RNA plus any other substances, such as ATP, that contain the bases.
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From page 184... ...
Since the ribosomes are rich in RNA, possibly it is the RNA that is concerned with protein synthesis. If this hypothesis was to be tested, new methods had to be developed.
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From page 185... ...
Of greater interest to us, Paul C.Zamecnik and his associates discovered that protein synthesis could also occur in cell-free fractions of cells. In this case, the layers containing the ribosomes and the supernatant were necessary.
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From page 186... ...
Proteins are not only huge molecules -- recall that hemoglobin is composed of nearly 600 amino acids -- but they are synthesized in an exact manner. Recall again that a difference in one amino acid in β chain of hemoglobin changes that molecule from the normal oxygencarrying substance to the defective molecule associated with sickle cell anemia.
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From page 187... ...
The next step is the union of the activated amino acid, now on the surface of the aminoacyl tRNA synthetase, with a tRNA molecule. Transfer RNA molecules are made on the DNA template by regions that can be called the tRNA genes.
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From page 188... ...
When the mRNA reaches the cytoplasm, it becomes closely associated with ribosomes. The tRNA molecules with their attached amino acids then come in contact with the mRNA.
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From page 189... ...
Theoretical considerations, as well as some data, suggested that the hypothetical substance might be a specific kind of RNA. Therefore the name messenger RNA seemed appropriate.
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From page 190... ...
Furthermore, the base composition of the messenger RNA must be complementary to the base composition of the DNA that makes it.
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From page 191... ...
: almost immediately the bacterial cells stop making their own specific molecules and begin to make phage DNA and phage proteins. If the messenger RNA hypothesis is correct, the events would be as follows: mRNA would be made on the phage DNA instead of on the bacterial DNA; this new and different mRNA would move to the ribosomes where it would give the instructions for making phage proteins.
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From page 192... ...
The serine becomes detached from the transfer RNA and then attaches to the amino acid on the adjacent tRNA molecule on the messenger RNA. This process is continued and other amino acids are added one by one to the growing polypeptide chain.
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From page 193... ...
They were able to obtain a cell-free system, from fractionated E coli cells, that would readily combine amino acids to form proteins.
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From page 194... ...
CAG glutamine UGU cysteine CGU arginine UGC cysteine CGC arginine UGA (none) CGA arginine UGG tryptophan CGG arginine AUU isoleucine GUU valine AUC isoleucine GUC valine AUA isoleucine GUA valine AUG methionine GUG valine ACU threonine GCU alanine ACC threonine GCC alanine ACA threonine GCA alanine ACG threonine GCG alanine AAU asparagine GAU aspartic acid AAC asparagine GAC aspartic acid AAA lysine GAA glutamic acid AAG lysine GAG glutamic acid AGU serine GGU glycine AGC serine GGC glycine AGA arginine GGA glycine AGG arginine GGG glycine be degenerate because usually more than one codon codes for each amino acid.
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From page 195... ...
The data seem to suggest that there are two active sites on the ribosome: the first where a tRNA molecule, with its amino acid, attaches to the mRNA; the second where the amino acid joins the polypeptide chain and is released from its tRNA. The events seem to be about as follows (Fig.
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From page 196... ...
A single ribosome is shown at three different times. At I an alanine tRNA is attaching to a GCA triplet on the mRNA.
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From page 197... ...
A shift now occurs: the glycine tRNA moves to the second position on the ribosome while the alanine tRNA is both ejected from moves to the right and the alanine tRNA is moved to the second site on the ribosome, as shown in II. The alanine molecule becomes attached to the polypeptide chain.
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From page 198... ...
Let us suppose that the single-stranded DNA that first enters the bacterial cell has a DNA sequence shown as the left DNA strand in Table 8–3. If so, then the newly synthesized complementary strand will have the sequence shown as the right strand.
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From page 199... ...
HEREDITY AND DEVELOPMENT: SECOND EDITION 199 Table 8–3 If both strands of DNA were involved in protein synthesis, this is what would happen: materials required for this synthesis are the four ribonucleoside triphosphates. (A ribonucleoside is composed of one of the four RNA bases, guanine, cytosine, uracil, or adenine combined with ribose; this plus three phosphate groups makes a ribonucleoside triphosphate; a nucleotide is a nucleoside plus one phosphate group.)
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From page 200... ...
The two end phosphates are split from the nucleoside triphosphates, thereby producing nucleotides, which are joined to form the DNA molecules. The primer DNA serves as a template and the newly synthesized DNA is identical to it, as one would expect from the Watson-Crick scheme.
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From page 201... ...
The messenger RNA molecule moves to the cytoplasm and becomes associated with ribosomes. Amino acids combine with specific tRNA molecules.
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From page 202... ...
Some kinds are abundant, others are rare. Such cells can divide into two daughter cells in half an hour, so in one hour the descendants of the original cell will have a total of 40 million protein molecules -- an incredible synthetic feat.
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From page 203... ...
Presumably the mechanism is the usual one: the tryptophan synthetase gene transmits through messenger RNA the code for joining amino acids in the specific way that makes tryptophan synthetase. The events beginning with the β-galactosidase gene and ending with the formation of the specific enzyme β-galactosidase are apparently the same.
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From page 204... ...
The regulator protein then binds at the operator site of the lac operon. If the RNA polymerase attaches to the promoter site to begin the transcription of mRNA, its passage along the DNA molecule is blocked by the regulator protein attached to the operator.
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From page 205... ...
When lactose is present, as shown in the lower portion of the diagram, mRNA can be made from genes z, y, and a and their specific proteins will be synthesized. The z gene is responsible for β-galactosidase.
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From page 206... ...
When the ribosomes are reading the mRNA, they add the amino acids called for by each codon until they reach one of the nonsense codons. At this point no amino acid can be added to the polypeptide chain, and the chain is terminated.
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From page 207... ...
PTASHNE, MARK, and WALTER GILBERT. ‘Genetic repressers.' Scientific American.
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From page 208... ...
1962. ‘Messenger RNA.' Scientific American February 1962.
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