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Genetics summary chapter 13 VU amsterdam

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This summary covers complete chaper 13 of genetics at the Vrije Universiteit Amsterdam.

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  • October 25, 2023
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Chapter 13 summary


- Translation: the process in which the sequence of codons within mRNA provides the information to
synthesize the sequence of amino acids that forms a polypeptide. One or more polypeptides then fold
and assemble to create a functional protein.

The RNA transcribed from the protein-encoding genes is called messenger RNA. The main function of the
genetic material is to encode for the production of proteins in the correct cell, at the proper time and in
suitable amounts.

Garrod proposed that some genes code for the production of enzymes

Garrod was interested in the disease called alkaptonuria, which is a disease where the patient’s body
accumulates abnormal levels of homogentisic acid (alkapton). This acid is excreted from the urine, causing it to
appear black when it is exposed to air. In addition, the disease is characterized by bluish-black discoloration of
cartilage and skin. Garrod proposed that the accumulation of homogentisic acid in these patients is due to a
defect enzyme, namely homogentisic acid oxidase.

He already knew that alkaptonuria is an inherited trait that follows an autosomal recessive pattern of
inheritance. Garrod proposed that a relationship exists between the inheritance of the trait and the inheritance
of a defective enzyme. Namely, if an individual inherited the mutant gene, she or he would not produce any
normal enzyme and would be unable to metabolize homogentisic acid. Therefore, he described alkaptonuria as
an inborn error of metabolism. This hypothesis was the first suggestion that a connection existed between the
function of genes and the production of enzymes.

Beadle and Tatum’s experiments with neurospora led them to propose the one-gene/one-enzyme
hypothesis

Consistent with Garrod’s hypothesis, the underlying assumption behind their approach was that a relationship
exists between genes and the production of enzymes. However, the quantitative nature of this relationship was
unclear. They focused on neurospora crassa, a common bread mold. Neurospora can be easily grown in the
laboratory and has a few nutritional requirements: a carbon source (sugar), inorganic salts, and the vitamin
biotin. Beadle and Tatum wanted to understand how enzymes are controlled by genes. They reasoned that a
mutation in a gene, causing a defect in an enzyme needed for the synthesis of an essential molecule, would
prevent that mutant strain from growing on minimal media, which contain only a carbon source, inorganic salts
and biotin. They concluded that a single gene controlled the synthesis of a single enzyme. This was referred to
as the one-gene/one-enzyme hypothesis.

1. Enzymes are only one category of proteins. All proteins are encoded by genes, and many of them do
not function as enzymes.
2. Some proteins are composed of two or more different polypeptides. Therefore, it more accurate to
say that a polypeptide-encoding gene encodes a polypeptide. The term polypeptide refers to the
structure; it is a linear structure of amino acids. By comparison, the term protein denotes function.
Some proteins are only composed of one polypeptide. In such cases, a single gene does not encode a
single protein. In other cases however, a functional protein is composed of two or more different
polypeptides. An example is hemoglobin, which is composed of two α-globin and two β-globin
polypeptides. In this case, the expression of two genes (α-globin and β-globin) is needed to create a
functional protein.
3. Many genes do not encode polypeptides.
4. One gene can encode multiple polypeptides due to alternative splicing and RNA editing.

The sequence of a protein-encoding gene provides a template for the synthesis of mRNA. In turn, the mRNA
contains the information to synthesize a polypeptide. During translation, the codons in mRNA provide
information to make a polypeptide with a specific amino acid sequence. The first step is to make mRNA which
happens through transcription. During the second step, translation, the information within mRNA is used to
make a polypeptide. The ability of mRNA to be translated into a specific sequence of amino acids relies on the
genetic code. The sequence of bases within an mRNA molecule provides coded information that is read in
groups of three nucleotides known as codons.

- The sequence of three bases in most codons specifies a particular amino acid. These codons are
termed as sense codons.

, Chapter 13 summary


- The codon AUG, which specifies methionine, functions as a start codon. It is the first codon that begins
the polypeptide sequence. The AUG codon can also be used to specify additional methionine’s within
the coding sequence.
- Three codons: UAA, UAG, UGA, are the stop codons. Stop codons are also known as termination
codon or nonsense codons.
- An mRNA molecule also has regions that precede the start codon and follow up the stop codon.
Because these regions do not encode a polypeptide, they are called 5’-untranslated region and 3’-
untranslated region.

The codons in mRNA are recognized by the anticodons in transfer RNA (tRNA) molecules. Anticodons are 3-
nucleotide sequences that are complementary to the codons in mRNA. The tRNA molecules carry the amino
acids that are specified by the codons of the mRNA. In this way, the order of the codons in mRNA dictates the
order of the amino acids within a polypeptide. The genetic code is composed of 64 different codons. Because
polypeptides are composed of 20 different amino acids, a minimum of 20 codons is needed to specify all of the
amino acids.

- Degeneracy: more than one codon can specify the same amino acid. For example GGU, GGC, GGA, and
GGG specify all for glycine. Such codons are termed synonymous codons.

The start codon (AUG) defines the reading frame of an mRNA – a series of codons determined by reading the
bases in groups of three, beginning with the start codon as a frame of reference (look at page 320). The genetic
code is nearly universal, but there are exceptions. The eukaryotic organelles known as mitochondria have their
own DNA, which includes a few protein-encoding genes. The mitochondrial genetic code differs from the
nuclear genetic code. The start codon for mitochondrial DNA is AUA and their stop codons are AGA and AGG.

Selenocysteine (sec) is found in several enzymes involved in oxidation-reduction reactions in bacteria, archaea
and eukaryotes. Pyrrolysine (Pyl) is found in a few enzymes of methane-producing archaea. Selenocysteine and
pyrrolysine are encoded by the codons UGA and UAG, which usually function as stop codons. Like the standard
20 amino acids, selenocysteine and pyrrolysine are bound to tRNAs that specifically carry them to the
ribosomes for their incorporation into polypeptides. The anticodon of the tRNA that carries selenocysteine is
complementary to the UGA codon and the tRNA that carries the pyrrolysine has an anticodon that is
complementary to UAG.

In the case of the codon that specifies for selenocysteine, UGA codon is followed by a sequence called the
selenocysteine insertion sequence (SECIS), which forms a stem-loop. In bacteria, SECIS may be located
immediately following the UGA codon, whereas in eukaryotes and archaea, the SECIS may be further
downstream in the 3’ -untranslated region of the mRNA. The SECIS is recognized by proteins that favor the
binding of a UGA codon to a tRNA carrying selenocysteine instead of binding of release factors that are needed
for polypeptide termination. Similarly, pyrrolysine incorporation may involve sequences downstream from a
UAG codon that forms a stem-loop.

Polypeptide synthesis has a directionality that parallels the order of codons in the mRNA. As a polypeptide is
made, a peptide bond is formed between the carboxyl group in the last amino acid of the polypeptide and the
amino group in the amino acid is being added. This occurs via condensation reactions that release a water
molecule. The first amino acid is said to be at the amino-terminus/ N-terminus, of the polypeptide. An amino
group (NH3) is found at this site. The first amino acid is specified by a codon that is near the 5’end of the
mRNA. The last amino acid in a completed polypeptide is located at the carboxyl-terminus/C-terminus. This
last amino acid is specified by a codon that is closer to the 3’ end of the mRNA.

Each amino acid, contains a unique side chain, or R group, that has its own particular chemical properties. This
letter R is a general designation for an amino acid side chain. The chemical properties of amino acids and their
sequences in a polypeptide are critical factors that determine the unique structure of that polypeptide.

- Primary structure: after translation, the end result is a polypeptide with a defined amino acid
sequence. This is the primary structure. Most polypeptides quickly adopt a compact 3D structure. The
folding process begins while the polypeptide is being translated. The progression from the primary
structure of a polypeptide to a 3D structure of a protein is dictated by the amino acid sequence of the
polypeptide. The chemical properties of the amino acid side chains (R groups) play a central role in
determining the folding pattern of a protein. In addition, the folding of some polypeptides is aided by
chaperones – proteins that bind to polypeptides and facilitate their proper folding.

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