Topic 8- Mutations and gene expression
Mutations:
Any change to the base sequence and these are caused by errors during DNA
replication and the rate of mutations can be increased by mutagenic agents.
- Substitution: bases are swapped for another
• Could form a stop codon so the nal protein can’t perform its normal function
• Different amino acid could form so the structure of the polypeptide would
change - affect function
• Same amino acid could be formed (degenerate code)
- Deletion: bases are removed which will cause a frame shift
- Addition: bases are added and could cause a frame shift
- Inversion: sequence of bases are reversed
- Duplication: Bases are repeated
- Translocation: a sequence of bases is moved from one location in the
genome to another → this could be a movement within the same
chromosome or movement to a different chromosome
The order of DNA bases in a gene determines the sequence of amino acids in a
particular polypeptide → mutation could lead to the sequence of the
polypeptide to change.
This means that the tertiary structure may change and so the protein will
not work properly.
If a gamete contains a mutation for a genetic disorder or a type of cancer is
fertilised the mutation will be present in the new foetus formed : these are
called hereditary mutations as they are passed on to the offspring.
Not all mutations affect the order of the amino acids due to the degenerate
nature of the genetic code
Additions, duplications and deletions will almost always change the amino acid
sequence of a polypeptide. This is because the mutations all change the number
fi
,of bases in the DNA code as they cause a frame shift or change the number of
bases in the DNA code.
Mutagenic agents include high energy ionising radiation and chemicals like
nitrogen dioxide
Mutagenic agents increase the rate of mutation by:
- Acting as a base: chemicals called base analogs can substitute for a base
during DNA replication, changing the base sequence in the new DNA. e.g. 5-
bromouracil can substitute for thymine to pair with guanine not adenine and
hence causes a substitution mutation in the new DNA
- Altering bases: Some chemicals can delete or alter bases e.g. alkylating
agents can add an alkyl group to guanine which changes the structure so that
it pairs with thymine not cytosine.
- Changing the structure of DNA: Radiation can cause problems during DNA
replication like UV causing 2 thymine bases to pair up
Cancer:
- Mutations in genes can cause uncontrolled cell growth
- Mutations that occur in cells after fertilisation are called acquired mutations.
If they occur in the genes that control the rate of cell division then it can
cause uncontrolled cell division
- If a cell divides uncontrollably, a tumour is produced: a mass of abnormal
cells. If they invade and destroy surrounding tissue they are called cancers.
Tumour suppressor genes:
They can be inactivated if a mutation occurs in the DNA sequence. When
functioning normally, they slow cell division by producing proteins that stop
cells dividing or cause them to self-destruct (apoptosis).
If a mutation occurs, then the protein isn't produced so the cells divide
uncontrollably resulting in a tumour
Proto-oncogenes:
Their effect can be increased if a mutation occurs in the DNA sequence. A
mutated proto-oncogene is called an oncogene.
, When functioning normally, they stimulate cell division by producing
proteins that stimulate cell division. If a mutation occurs in a proto-oncogene
then the gene can become overactive to stimulate cells to divide uncontrollably
so the rate of division increases, resulting in a tumour.
Malignant : cancerous tumours that grow rapidly, invade and destroy
surrounding tissues. Cells can break off the tumours and spread to other parts of
the body in the bloodstream or lymphatic system.
Benign : non cancerous tumours that grow slower than malignant tumours and
are often covered in brous tissue that stops cells invading other tissues. They
are usually harmless but can cause blockages and put pressure on organs. Some
can become malignant.
Tumour cells are different to normal cells:
- They have an irregular shape
- Larger and darker nucleus
- Don't produce all the proteins needed to function correctly
- Have different antigens on their surface
- Don’t respond to growth regulating processes and divide by mitosis more
frequently than normal cells.
Abnormal methylation of cancer related genes can cause tumour growth:
- Methylation is adding a methyl group onto something
- Methylation of DNA is an important method of regulating gene expression
as it can control whether or not a gene is transcribed and translated
- It plays a key role in many processes in the body. When it happens too much
or too little, it causes a problem (hypermethylation & hypomethylation)
Abnormal methylation:
- When tumour suppressor genes are hypermethylated, the genes are not
transcribed so proteins that slow cell division are not made. The cells can
divide uncontrollably by mitosis and tumours can develop.
- Hypomethylation of proto-oncogenes causes them to act as oncogenes so
increase the production of the proteins that cause cell division. This
fi
Mutations:
Any change to the base sequence and these are caused by errors during DNA
replication and the rate of mutations can be increased by mutagenic agents.
- Substitution: bases are swapped for another
• Could form a stop codon so the nal protein can’t perform its normal function
• Different amino acid could form so the structure of the polypeptide would
change - affect function
• Same amino acid could be formed (degenerate code)
- Deletion: bases are removed which will cause a frame shift
- Addition: bases are added and could cause a frame shift
- Inversion: sequence of bases are reversed
- Duplication: Bases are repeated
- Translocation: a sequence of bases is moved from one location in the
genome to another → this could be a movement within the same
chromosome or movement to a different chromosome
The order of DNA bases in a gene determines the sequence of amino acids in a
particular polypeptide → mutation could lead to the sequence of the
polypeptide to change.
This means that the tertiary structure may change and so the protein will
not work properly.
If a gamete contains a mutation for a genetic disorder or a type of cancer is
fertilised the mutation will be present in the new foetus formed : these are
called hereditary mutations as they are passed on to the offspring.
Not all mutations affect the order of the amino acids due to the degenerate
nature of the genetic code
Additions, duplications and deletions will almost always change the amino acid
sequence of a polypeptide. This is because the mutations all change the number
fi
,of bases in the DNA code as they cause a frame shift or change the number of
bases in the DNA code.
Mutagenic agents include high energy ionising radiation and chemicals like
nitrogen dioxide
Mutagenic agents increase the rate of mutation by:
- Acting as a base: chemicals called base analogs can substitute for a base
during DNA replication, changing the base sequence in the new DNA. e.g. 5-
bromouracil can substitute for thymine to pair with guanine not adenine and
hence causes a substitution mutation in the new DNA
- Altering bases: Some chemicals can delete or alter bases e.g. alkylating
agents can add an alkyl group to guanine which changes the structure so that
it pairs with thymine not cytosine.
- Changing the structure of DNA: Radiation can cause problems during DNA
replication like UV causing 2 thymine bases to pair up
Cancer:
- Mutations in genes can cause uncontrolled cell growth
- Mutations that occur in cells after fertilisation are called acquired mutations.
If they occur in the genes that control the rate of cell division then it can
cause uncontrolled cell division
- If a cell divides uncontrollably, a tumour is produced: a mass of abnormal
cells. If they invade and destroy surrounding tissue they are called cancers.
Tumour suppressor genes:
They can be inactivated if a mutation occurs in the DNA sequence. When
functioning normally, they slow cell division by producing proteins that stop
cells dividing or cause them to self-destruct (apoptosis).
If a mutation occurs, then the protein isn't produced so the cells divide
uncontrollably resulting in a tumour
Proto-oncogenes:
Their effect can be increased if a mutation occurs in the DNA sequence. A
mutated proto-oncogene is called an oncogene.
, When functioning normally, they stimulate cell division by producing
proteins that stimulate cell division. If a mutation occurs in a proto-oncogene
then the gene can become overactive to stimulate cells to divide uncontrollably
so the rate of division increases, resulting in a tumour.
Malignant : cancerous tumours that grow rapidly, invade and destroy
surrounding tissues. Cells can break off the tumours and spread to other parts of
the body in the bloodstream or lymphatic system.
Benign : non cancerous tumours that grow slower than malignant tumours and
are often covered in brous tissue that stops cells invading other tissues. They
are usually harmless but can cause blockages and put pressure on organs. Some
can become malignant.
Tumour cells are different to normal cells:
- They have an irregular shape
- Larger and darker nucleus
- Don't produce all the proteins needed to function correctly
- Have different antigens on their surface
- Don’t respond to growth regulating processes and divide by mitosis more
frequently than normal cells.
Abnormal methylation of cancer related genes can cause tumour growth:
- Methylation is adding a methyl group onto something
- Methylation of DNA is an important method of regulating gene expression
as it can control whether or not a gene is transcribed and translated
- It plays a key role in many processes in the body. When it happens too much
or too little, it causes a problem (hypermethylation & hypomethylation)
Abnormal methylation:
- When tumour suppressor genes are hypermethylated, the genes are not
transcribed so proteins that slow cell division are not made. The cells can
divide uncontrollably by mitosis and tumours can develop.
- Hypomethylation of proto-oncogenes causes them to act as oncogenes so
increase the production of the proteins that cause cell division. This
fi
