Section
11: The last and final section!!!!!
I.
How genes work
II.
How genes control the production of proteins
III.
Transcription: Information flow from DNA to RNA
IV.
The genetic code
V.
Translation: Information flow from mRNA to protein
VI.
The effect of mutations on protein synthesis
VII.
Putting it all together: from gene to phenotype
I. How genes work
v Genes
control the manufacturing of proteins.
Proteins are essential to life.
They can provide structural support, transport materials through the
body, defend against disease-causing organisms, and serve as enzymes.
v How
do genes control phenotype of an organism? History:
o
Archibald Garrod, a British physician,
studied several inherited human metabolic disorders
§ In
1902, he argued that these disorders were caused by an inability of the body to
produce specific enzymes
§ Alkaptonuria
o
Garrod and his collaborator, William
Bateson, suggested that genes work by controlling the production of
enzymes. This was only partially
correct, as genes control the production of all proteins, not just enzymes.
Furthermore, a few genes do not directly specify proteins, but instead
contain instructions for building several kinds of RNA molecules that are used
in the construction of proteins.
v Genes
are DNA sequences that contain information for the building of one of several
types of RNA molecules used to make proteins.
o
RNA: single-stranded, can assume various
nonhelical shapes; each nucleotide in RNA is composed of a sugar, a phosphate
group, and one of four nitrogen-containing bases. However, RNA uses the sugar ribose, and the
base Uracil (U) replaces the base thymine (T). When RNA pairs with DNA or other
RNA, it does so as follows: Adenine pairs with Uracil, and Guanine pairs with
Cytosine.
v Three
types of RNA are involved in the production of proteins
o
mRNA
o
rRNA
o
tRNA
II. How genes control
the production of proteins
v TWO STEPS:
transcription and translation
o
In transcription, mRNA molecules are made
using information in the DNA sequence of a gene. The base sequence of that mRNA molecule
specifies the amino acid sequence of a protein.
o
In translation, the information in the
mRNA molecule is used to build the protein, with the help of several rRNA molecules,
many tRNA molecules, and a number of proteins.
III. Transcription:
Information flow from DNA to RNA
o
Transcription occurs in the nucleus of eukaryotic cells.
o
Transcription is similar to DNA
replication because one strand of DNA is used as a template from which a new
strand (in this case, a strand of mRNA) is formed. However, transcription differs from replication
in 3 important ways:
§ Different
enzyme guides the process: RNA
polymerase
§ Only
the small portion of a DNA molecule that includes a particular gene is
transcribed into mRNA.
§ Produces
a single-stranded mRNA molecule
o
Transcription begins when RNA polymerase
binds to a segment of DNA near the beginning of the gene, called a promoter.
§ A
promoter contains several specific sequences of 6-10 bases that help bind RNA
polymerase.
o
Once bound, the RNA polymerase unwinds
the DNA double helix at the beginning of the gene, thus separating a short
portion of the two strands. Then, the
enzyme begins to construct an mRNA molecule.
The side of the DNA strand with the promoter (template strand) is used
as a template for the building of the mRNA strand.
§ How
do the bases pair up when the mRNA strand is built? Do the example below:
T T A T G G C A C C G
§ How
is this different from the sequence that would have been built during DNA
replication?
o
By complementary base pairing with the
DNA template strand, the mRNA sequence completely duplicates (except that U
substitutes for T) the sequence of the other
DNA strand, the coding strand. This
is how the information in the DNA is directly copied to mRNA.
o
The addition of bases to the mRNA strand
continues until the RNA polymerase reaches a sequence of bases called a terminator, at which point
transcription ends and the newly formed mRNA molecule separates from the DNA
template. The two strands of the gene’s
DNA then bond back together, ready to be used again when needed by the cell.
§ In
eukaryotic cells, some modification must occur to the mRNA strand before it can
leave the nucleus. Introns are removed,
leaving only exons, and some strands receive a guanine cap and a poly A tail.
o
After transcription is complete, the
mRNA molecule is transported out of the nucleus, through a nuclear pore, to a
ribosome in the cytoplasm, where the protein specified by the gene will be
built.
IV. The Genetic Code
o
In the genetic code, each amino acid is
specified by a sequence of three mRNA bases, called a codon, in an mRNA
molecule. Each mRNA base is part of only
one codon. Let’s consider an example:
§ mRNA
sequence: UUCACUCAG
§ codons:
UUC ACU CAG
§ amino
acids: phenylalanine threonine glutamine
o
See the genetic code below:
o
When reading the code, the cell begins
at a fixed starting point on an mRNA molecule, called a start codon (AUG), and
ends up at one of several stop codons (UGA, UAA, UAG). By beginning at a fixed point, the cell
ensures that the message from the gene does not become scrambled.
§ Ex:
What would occur if the first U in our original mRNA sequence was skipped
over?
·
mRNA: UCACUCAG
·
codons:
·
amino acids:
o
The genetic code has several significant
characteristics:
§ Unambiguous
§ Redundant
§ Universal
V. Translation:
information flow from mRNA to protein
o
This is the second major step in the
process by which genes specify proteins.
It occurs at ribosomes, which
are composed of several different sizes of rRNA molecules and more than 50
different proteins. The ribosomes are
molecular “machines” that make the covalent bonds linking amino acids together
in a particular protein.
o
A crucial role in building proteins at
ribosomes is also played by tRNA molecules.
All tRNA has a similar strcture with two binding sites. At one end, each tRNA molecule has a site
that binds to a particular amino acid.
At the other end, each tRNA molecule has a sequence of 3 nitrogen bases,
called an anticodon that binds by
complementary base pairing with a particular mRNA codon.
§ Each
tRNA molecule binds to and carries the amino acid that is specified by the mRNA
codon to which it can bind; for example, the tRNA that binds to the mRNA codon
AGC carriers the amino acid serine.
o
Steps of translation:
§ The
first step of translation is the binding of an mRNA molecule to a
ribosome. Translation begins at the
start codon: the AUG codon nearest to the region where mRNA is bound to the
ribosome. A tRNA molecule carrying the
amino acid methionine binds to the start codon.
§ Next,
another tRNA molecule carrying the appropriate amino acid, binds to the second
codon on the mRNA molecule.
§ The
ribosome then forms a covalent bond between the first amino acid (methionine)
and the second amino acid. At the same
time that the bond between the first two amino acids is formed, the bond
between the first tRNA and the methionine it carries is broken.
§ Next,
the ribosome moves to the third mRNA codon, and the first tRNA is released from
the mRNA.
§ Once
the first tRNA is released, a tRNA molecule binds to the third codon, bringing
with it the third amino acid of the growing amino acid chain. The ribosome links the first two amino acids
to the third one, and then releases the second tRNA.
§ This
process continues until a stop codon is reached, at which point the mRNA
molecule and the completed amino acid chain both separate from the
ribosome. The new protein then folds
into its compact, specific three-dimensional shape.
IV. The effects of
mutations on protein synthesis
v Mutations
can alter one or many bases in a gene’s DNA sequence
o
Substitution mutation:
o
Insertion:
o
Deletion:
v Mutations
can cause a change in protein function
o
Frameshift mutations can alter the
identity of many of the amino acids in the protein and/or stop protein
synthesis before it is complete.
o
Any mutation that alters an enzyme’s
binding site (region of enzyme that binds to substrate) is usually
harmful. This changes the way an enzyme
acts, decreasing or destroying its function.
o
Mutations that insert or delete a series
of bases causes the protein to have extra or missing amino acids, which can
change the protein’s shape and hence its function.
o
Sometimes, changing a few bases in a
gene’s DNA sequence has little or no effect.
§ Silent
substitutions:
o
A few mutations may be beneficial. For example, changes to the binding region of
a protein might improve its efficiency or allow it to take on new and useful
functions, such as reacting with a new substrate.
V. Putting it all
together: from gene to phenotype
v Humans
have approximately 25,000 genes arranged linearly on 23 pairs of chromosomes. More than 99% of these genes code for
proteins; the rest code for RNA molecules such as tRNA and rRNA. One thing to note: transcription is similar
in all genes, including those that specify tRNA and rRNA molecules. However, translation does not occur for those
genes because the tRNA and rRNA molecules are their final product.
v Each
gene is composed of a segment of DNA on a chromosome and consists of a sequence
of the four bases adenine, thymine, guanine, and cytosine. The particular sequence of bases in the DNA
of the gene specifies the amino acid sequence of the gene’s protein product.
v The
two major steps in the synthesis of a protein from the information in its
corresponding gene are transcription and translation. In transcription, the sequence of bases in a
gene is used as a template to produce an mRNA molecule. The cell then transports this mRNA molecule
out of the nucleus to a ribosome in the cytoplasm, where translation occurs. In translation, the sequence of bases in the
mRNA molecule is used as a template to make the gene’s protein product by
stringing together the correct sequence of amino acids.
v Control
of gene expression
o
DNA packing
o
Regulation of transcription
o
Breakdown of mRNA
o
Inhibition of translation
o
Regulation after translation
o
Breakdown of protein
v Development
in eukaryotes relies on gene cascades and homeotic genes
o
Gene cascade: when a series of genes are
turned on one after another; protein products of certain genes interact with one
another and with signals from the environment to turn on different sets of
genes in different cells. Proteins
produced by those newly activated genes then interact with one another and with
the environment to turn on still more genes, and so on.
o
Homeotic genes: play a central role in
the control of gene cascades; control the expression of a series of other genes
whose proteins direct the development of the organism
§ Defective
versions of homeotic genes can have striking phenotypic effects.
§ At
different times during an individual’s development, different homeotic genes
are active in the body’s different cell types.