Download Gene7-01

Chapter 1
Genes are DNA
DNA是遗传物质
本
章
主
要
内
容
DNA为双螺旋
DNA的复制是半保留的
通过碱基配对进行核酸杂交
突变改变了DNA的序列
突变集中于热点
顺反子是单个DNA片断
多重等位基因的种类
DNA的物理交换导致重组
遗传密码是三联体
细菌的基因和蛋白是共线性的
顺式作用点和反式作用分子
遗传信息可由DNA或者RNA提供
1.1
Introduction
Figure 1.1 A brief
history of genetics.
Genes are
DNA
1.2 DNA is the genetic material
Avirulent mutants of a virus have lost the capacity to
infect a host cell productively, that is, to make more
virus.
Transfection of eukaryotic cells is the acquisition of
new genetic markers by incorporation of added DNA.
Transforming principle is DNA that is taken up by a
bacterium and whose expression then changes the
properties of the recipient cell.
1.2 DNA is the
genetic material
Figure 1.2 The
transforming principle is
DNA.
1.2 DNA is the
genetic material
Figure 1.3 The genetic
material of phage T2 is
DNA.
1.2 DNA is the
genetic material
Figure 1.4 Eukaryotic cells
can acquire a new
phenotype as the result of
transfection by added
DNA.
1.3 DNA is a double helix
Antiparallel strands of the double helix are organized in
opposite orientation, so that the 5′ end of one strand is
aligned with the 3′ end of the other strand.
Base pairing describes the specific (complementary)
interactions of adenine with thymine or of cytosine with
thymine in a DNA double helix (the former is replaced by
adenine with uracil in double helical RNA).
Complementary base pairs are defined by the pairing
reactions in double helical nucleic acids (A with T in DNA
or with U in RNA, and C with G).
Supercoiling describes the coiling of a closed duplex DNA
in space so that it crosses over its own axis.
1.3 DNA is a
double helix
Figure 1.5
A polynucleotide
chain consists of a
series of 5￠-3￠
sugar-phosphate
links that form a
backbone from
which the bases
protrude
1.3 DNA is a
double helix
Figure 1.6 The
double helix
maintains a constant
width because
purines always face
pyrimidines in the
complementary A-T
and G-C base pairs.
The sequence in the
figure is T-A, C-G, A-
1.3 DNA is a
double helix
Figure 1.7 Flat base
pairs lie
perpendicular to the
sugar-phosphate
backbone.
1.3 DNA is a
double helix
Figure 1.8 The two
strands of DNA form
a double helix.
1.4 DNA replication is semicon-servative
DNA polymerases are enzymes that synthesize a
daughter strand(s) of DNA (under direction from a DNA
template). May be involved in repair or replication.
DNAases are enzymes that attack bonds in DNA.
Endonucleases cleave bonds within a nucleic acid chain;
they may be specific for RNA or for single-stranded or
double-stranded DNA.
Exonucleases cleave nucleotides one at a time from the
end of a polynucleotide chain; they may be specific for
either the 5′ or 3′ end of DNA or RNA.
1.4
DNA
replication
is
semicon-servative
Replication fork is the point at which strands of parental
duplex DNA are separated so that replication can
proceed.
Ribonucleases are enzymes that degrade RNA.
Exo(ribo)nucleases work progressively, typically
degrading one base at a time from the 3′ end toward the
5 ′ end. Endo(ribo)nucleases make single cuts within the
RNA chain.
RNA polymerases are enzymes that synthesize RNA
using a DNA template (formally described as DNAdependent RNA polymerases).
RNAases are enzymes that degrade RNA.
Semiconservative replication is accomplished by
separation of the strands of a parental duplex, each then
acting as a template for synthesis of a complementary
strand.
1.4 DNA
replication is
semiconservative
Figure 1.9 Base
pairing provides the
mechanism for
replicating DNA.
1.4 DNA
replication is
semiconservative
Figure 1.10
Replication of DNA
is semiconservative.
1.4 DNA replication is semiconservative
Figure 1.11 The replication fork is the region of DNA in which there is a transition
from the unwound parental duplex to the newly replicated daughter duplexes.
1.5 Nucleic acids hybridize by base pairing
Denaturation of DNA or RNA describes its conversion
from the double-stranded to the single-stranded state;
separation of the strands is most often accomplished by
heating.
Hybridization is the pairing of complementary RNA and
DNA strands to give an RNA-DNA hybrid.
Melting of DNA means its denaturation.
Melting temperature of DNA is the mid-point of the
transition when duplex DNA to denatured by heating to
separate into single strands.
1.5
Nucleic acids
hybridize by
base pairing
Figure 1.12 Base
pairing occurs in
duplex DNA and also
in intra- and intermolecular
interactions in
single-stranded RNA
(or DNA).
1.5
Nucleic acids
hybridize by
base pairing
Figure 1.13
Denatured single
strands of DNA can
renature to give the
duplex form.
1.5
Nucleic acids
hybridize by
base pairing
Figure 1.14 Filter
hybridization establishes
whether a solution of
denatured DNA (or RNA)
contains sequences
complementary to the
strands immobilized on
the filter.
1.6 Mutations change the sequence of DNA
Background level of mutation describes the rate at which
sequence changes accumulate in the genome of an
organism. It reflects the balance between the occurrence
spontaneous mutations and their remomval by repair
systems, and is characteristic for any species.
Deletions are generated by removal of a sequence of DNA,
the regions on either side being joined together.
result from the action of a mutagen (which may act directly
on the bases in DNA) or indirectly, but in either case the
result is a change in the sequence of DNA.
are identified by the presence of an additional stretch of
base pairs in DNA.
1.6 Mutations change the sequence of DNA
Leaky mutants have some residual function, either
because the mutant protein is partially active (in the
case of a missense mutation), or because a small
amount of wild-type protein is made (in the case of a
nonsense mutation).
Mutagens increase the rate of mutation by inducing
changes in DNA sequence, directly or indirectly.
Point mutations are changes involving single base
pairs.
Revertants are derived by reversion of a mutant cell or
organism.
Spontaneous mutations occur as the result of natural
effects, due either to mistakes in DNA replication or to
environmental damage.
1.6 Mutations change the sequence of DNA
Suppression describes the occurrence of changes that
eliminate the effects of a mutation without reversing the original
change in DNA.
Suppressor (extragenic) is usually a gene coding a mutant
tRNA that reads the mutated codon either in the sense of the
original codon or to give an acceptable substitute for the
original meaning.
Transition is a mutation in which one pyrimidine is substituted
by the other or in which one purine is substituted for the other.
Transversion is a mutation in which a purine is replaced by a
pyrimidine or vice versa.
1.6 Mutations
change the
sequence of
DNA
Figure 1.15
Mutations can be
induced by chemical
modification of a
base.
1.6 Mutations
change the
sequence of
DNA
Figure 1.16
Mutations can be
induced by the
incorporation of base
analogs into DNA.
1.7 Mutations are concentrated at hotspots
Back mutation reverses the effect of a mutation that had
inactivated a gene; thus it restores wild type.
Forward mutations inactivate a wild-type gene.
Hotspot is a site at which the frequency of mutation (or
recombination) is very much increased.
Modified bases are all those except the usual four from which
DNA (T, C, A, G) or RNA (U, C, A, G) are synthesized; they
result from postsynthetic changes in the nucleic acid.
Neutral substitutions in a protein are those changes of amino
acids that do not affect activity.
Silent mutations do not change the product of a gene.
1.7 Mutations
are
concentrated
at hotspots
Figure 1.17
Spontaneous
mutations occur
throughout the lacI
gene of E. coli, but
are concentrated at
a hotspot.
1.7 Mutations
are
concentrated
at hotspots
Figure 1.18 The
deamination of 5methylcytosine produces
thymine (causing C-G to
T-A transitions), while the
deamination of cytosine
produces uracil (which
usually is removed and
then replaced by cytosine).
1.7 Mutations
are
concentrated
at hotspots
Figure 1.15
Mutations can be
induced by chemical
modification of a
base.
1.8 A cistron is a single stretch of DNA
Cistron is the genetic unit defined by the cis/trans test;
equivalent to gene.
Complementation group is a series of mutations unable to
complement when tested in pairwise combinations in trans;
defines a genetic unit (the cistron).
Gene (cistron) is the segment of DNA involved in producing a
polypeptide chain; it includes regions preceding and following
the coding region (leader and trailer) as well as intervening
sequences (introns) between individual coding segments
(exons).
One gene : one enzyme hypothesis is the basis of modern
genetics: that a gene is a stretch of DNA coding for a single
polypeptide chain.
1.8 A cistron is
a single
stretch of
DNA
Figure 1.19 Genes code
for proteins; dominance
is explained by the
properties of mutant
proteins. A recessive
allele does not contribute
to the phenotype
because it produces no
protein (or protein that is
nonfunctional).
1.8 A cistron is
a single
stretch of
DNA
Figure 1.20 The
cistron is defined by
the complementation
test. Genes are
represented by bars;
red stars identify
sites of mutation.
1.9 The nature of multiple alleles
Gain-of-function mutation represents acquisition of a new activity.
It is dominant.
Leaky mutants have some residual function, either because the
mutant protein is partially active (in the case of a missense
mutation), or because a small amount of wild-type protein is
made (in the case of a nonsense mutation).
Loss-of-function mutation inactivates a gene. It is recessive.
Null mutation completely eliminates the function of a gene,
usually because it has been physically deleted.
Polymorphism refers to the simultaneous occurrence in the
population of genomes showing allelic variations (as seen either
in alleles producing different phenotypes or-for example-in
1.9 The nature
of multiple
alleles
Figure 1.19 Genes code
for proteins; dominance is
explained by the
properties of mutant
proteins. A recessive allele
does not contribute to the
phenotype because it
produces no protein (or
protein that is
nonfunctional).
1.9 The nature of multiple alleles
Figure 1.21 The w locus has an extensive series of alleles, whose
phenotypes extend from wild-type (red) color to complete lack of
pigment.
1.9 The nature
of multiple
alleles
Figure 1.22 The ABO
blood group locus codes
for a galactosyltransferase
whose specificity
determines the blood
group.
1.10 Recombination occurs by
physical exchange of DNA
Bivalent is the structure containing all four chromatids (two
representing each homologue) at the start of meiosis.
Breakage and reunion describes the mode of genetic
recombination, in which two DNA duplex molecules are broken
at corresponding points and then rejoined crosswise (involving
formation of a length of heteroduplex DNA around the site of
joining).
Chiasma (pl. chiasmata) is a site at which two homologous
chromosomes appear to have exchanged material during
meiosis.
Crossing-over describes the reciprocal exchange of material
between chromosomes that occurs during meiosis and is
responsible for genetic recombination.
Hybrid DNA is another term for heteroduplex DNA.
1.10
Recombination
occurs by physical
exchange of DNA
Figure 1.23 Chiasma
formation is
responsible for
generating
recombinants.
1.10
Recombination
occurs by physical
exchange of DNA
Figure 1.24
Recombination
involves pairing
between
complementary
strands of the two
parental duplex
DNAs.
1.10
Recombination
occurs by physical
exchange of DNA
Figure 1.13
Denatured single
strands of DNA can
renature to give the
duplex form.
1.11 The genetic code is triplet-- Key terms
Codon is a triplet of nucleotides that represents an amino acid or a
termination signal.
Frameshift mutation results from an insertion or deletion that
changes the phase of triplets, so that all codons are misread after
the site of mutation.
Genetic code is the correspondence between triplets in DNA (or
RNA) and amino acids in protein.
Initiation codon is a special codon (usually AUG) used to start
synthesis of a protein.
ORF is an open reading frame; presumed likely to code for a
protein.>
Reading frame is one of three possible ways of reading a nucleotide
sequence as a series of triplets.
Suppressor (extragenic) is usually a gene coding a mutant tRNA
that reads the mutated codon either in the sense of the original
codon or to give an acceptable substitute for the original meaning.
Termination codon is one of three (UAG, UAA, UGA) that causes
protein synthesis to terminate.
1.11
The genetic code is
triplet
Figure 1.25
Frameshift mutations
show that the
genetic code is read
in triplets from a
fixed starting point.
1.11 The genetic code is triplet
Figure 1.26 An open reading frame starts with AUG and
continues in triplets to a termination codon. Blocked reading
frames may be interrupted frequently by termination codons.
1.12 The relationship between coding sequences and proteins
Coding region is a part of the gene that represents a
protein sequence.
Leader of a protein is a short N-terminal sequence
responsible for passage into or through a membrane.
RNA splicing is the process of excising the sequences in
RNA that correspond to introns, so that the sequences
corresponding to exons are connected into a continuous
mRNA.
Trailer is a nontranslated sequence at the 3´ end of an
mRNA following the termination codon.
Transcription is synthesis of RNA on a DNA template.
Translation is synthesis of protein on the mRNA template.
1.12
The relationship
between coding
sequences and
proteins
Figure 1.27
The recombination
map of the
tryptophan
synthetase gene
corresponds with the
amino acid
sequence of the
protein.
1.12 The relationship between coding sequences and proteins
Figure 1.28
RNA is
synthesized
by using
one strand
of DNA as a
template for
complement
ary base
pairing.
1.12 The relationship between coding sequences and proteins
Figure 1.29
The gene
may be
longer than
the
sequence
coding for
protein.
1.12
The relationship
between coding
sequences and
proteins
Figure 1.30
Gene expression is a
multistage process.
1.12
The relationship
between coding
sequences and
proteins
Figure 2.10
Interrupted genes
are expressed via a
precursor RNA.
Introns are removed
when the exons are
spliced together. The
mRNA has only the
sequences of the
exons.
1.12
The relationship
between coding
sequences and
proteins
Figure 5.16
Eukaryotic mRNA
is modified by
addition of a cap
to the 5￠ end
and poly(A) to
the 3￠ end.
1.13 cis-acting sites and trans-acting molecules
cis- configuration describes two sites
on the same molecule of DNA.
Trans- configuration of two sites
refers to their presence on two
different molecules of DNA
(chromosomes).
1.13 cis-acting
sites and transacting molecules
Figure 1.20
The cistron is
defined by the
complementation test. Genes
are represented
by bars; red stars
identify sites of
mutation.
1.13 cis-acting
sites and transacting molecules
Figure 1.31
Control sites in
DNA provide
binding sites for
proteins; coding
regions are
expressed via the
synthesis of RNA.
1.13 cis-acting
sites and transacting molecules
Figure 1.32
A cis-acting site
controls the
adjacent DNA but
does not
influence the
other allele.
1.13 cis-acting
sites and transacting molecules
Figure 1.33
A trans-acting
mutation in a
protein affects
both alleles of a
gene that it
controls.
1.14 Genetic informationcan be
provided by DNA or RNA
Central dogma describes the basic nature of genetic information:
sequences of nucleic acid can be perpetuated and interconverted by
replication, transcription, and reverse transcription, but translation from
nucleic acid to protein is unidirectional, because nucleic acid sequences
cannot be retrieved from protein sequences.
Prion is a proteinaceous infectious agent, which behaves as an
inheritable trait, although it contains no nucleic acid. Examples are PrPSc,
the agent of scrapie in sheep and bovine spongiform encephalopathy,
and Psi, which confers an inherited state in yeast.
Reverse transcription is synthesis of DNA on a template of RNA;
accomplished by reverse transcriptase enzyme.
Scrapie is a infective agent made of protein.
Virion is the physical virus particle (irrespective of its ability to infect cells
and reproduce).
Viroid is a small infectious nucleic acid that does not have a protein coat.
1.14 Genetic
information can
be provided by
DNA or RNA
Figure 1.34
The central dogma
states that
information in
nucleic acid can be
perpetuated or
transferred, but the
transfer of
information into
protein is irreversible.
1.14 Genetic
information can
be provided by
DNA or RNA
Figure 1.35
Double-stranded
and singlestranded nucleic
acids both
replicate by
synthesis of
complementary
strands governed
by the rules of
base pairing.
1.14 Genetic
information can
be provided by
DNA or RNA
Figure 1.36
The amount of
nucleic acid in the
genome varies
over an enormous
range.
1.14 Genetic information can be provided by DNA or RNA
Figure 1.37 PSTV RNA is a circular molecule that forms an
extensive double-stranded structure, interrupted by many interior
loops. The severe and mild forms differ at three sites.
1.15 Summary
1. Two classic experiments proved that DNA is
the genetic material.
2. DNA is a double helix consisting of
antiparallel strands in which the nucleotide units
are linked by 5 3 phosphodiester bonds.
3. A stretch of DNA may code for protein.
4. A chromosome consists of an uninterrupted
length of duplex DNA that contains many genes.
5. A gene may have multiple alleles. Recessive
alleles are caused by a loss-of-function.
1.15 Summary
6. A mutation consists of a change in the sequence
of A·T and G·C base pairs in DNA.
7. The natural incidence of mutations is increased
by mutagens.
8. Forward mutations occur at a rate of ~106 per
locus per generation; back mutations are rarer.
9. Although all genetic information in cells is carried
by DNA, viruses have genomes of double-stranded
or single-stranded DNA or RNA.