3.8 The control of gene expression Flashcards
substitution of bases
A nucleotide in a section of DNA molecule is replaced by another nucleotide that has a different base.
Depending on what new base is substituted, there are 3 possible outcomes:
Formation of 1 of the 3 stop codons. Stop the polypeptide production prematurely.
Final protein will be significantly different and couldn’t perform its normal function
Formation of a codon for a different amino acid, meaning the structure of the polypeptide produced would differ in a single amino acid.
The protein may differ in shape and not function properly
Formation of a different codon but 1 that produces a codon for the same amino acid before.
This is because genetic code is degenerate and so most amino acids have more than 1 codon.
deletion of base
A loss of a nucleotide base from a DNA sequence.
Minor though the loss of a single base might seem, the impact on the phenotype may be large.
The 1 deleted base will cause what is known as a frame shift because the reading frame that contains each 3 letters of the code has been shifted left by 1 base.
The gene is now read in the wrong 3-base groups and the coded information is altered.
1 deleted base at the very start could alter every triplet in the sequence
1 deleted base towards the end could have a smaller impact but can still have consequences.
other types of gene mutation
Addition of bases- an extra base is inserted in the sequence. Usually has a similar effect to base deletion in that there is usually a frame shift and the whole sequence of triplets is altered. Frame shift is to the right.
Duplication of bases- 1 or more bases are repeated. Causes a frame shift to the right.
Inversion of bases- a group of bases are separated from the DNA sequence and re-join at the same position but in the reverse order.
Translocation of bases- group of bases become separated from the DNA sequence on 1 chromosome and become inserted in the DNA sequence of a different chromosome. Translocations often have significant effect on gene expression leading to an abnormal phonotype. Effects include developing cancer and infertility
mutation causes
Can occur spontaneously during DNA replication.
Spontaneous mutations are permanent changes in DNA that occur without any outside influence.
Occur with a predictable frequency
This basic mutation rate can be increased by outside factors known as mutagenic agents or mutagens. These include:
High energy ionising radiation- for example alpha and beta particles as well as short wavelength radiation such as X-rays and ultra violet light. These can disrupt the structure of DNA as it ionises DNA.
Chemicals such as nitrogen dioxide may directly alter the structure of DNA or interfere with transcription. Benzopyrene, a constituent of tobacco is a powerful mutagen that inactivates a tumour-suppressor gene TP53 leading to cancer
cost and benefits of mutations
They produce the genetic diversity necessary for the natural selection and speciation. On the other hand they are almost always harmful and produce an organism that is less well suited to its environment. Mutations that occur in body cells rather than in gametes leading to disruption of normal cellular activities such as cell division
stem cells
an organism develops from a single fertilised egg. Cells such as fertilised specialisation is irreversible in most animal cells.
In mature mammals, only a few cells retain the ability to differentiate into other cells.
Stem cells are undifferentiated dividing cells that occur in adult animal tissues and need to be constantly replaced. They therefore have the ability to divide to form an identical copy of themselves in the process of self-renewal.
where stem cells come from
Embryonic stem cells- come from embryos in the early stage of development. Can differentiate into any type of cell in the initial stages of development
Umbilical chord blood stem cells- derived from the umbilical chord blood and are similar to adult stem cells
Placental stem cells- found in the placenta and develop into specific types of cell
Adult stem cells- found in body tissue of foetus through to adult. Are specific to a particular tissue or organ within which they produce the cells to maintain and repair tissues throughout an organisms life.
totipotency
an organism develops from a single fertilised egg. Cells such as fertilised eggs, which can mature into any type of cell, are known as totipotent cells.
The early cells that are derived from the fertilised egg are totipotent. These later differentiate and become specialised for a particular function. This is because during the process of cell specialisation, only some of genes are expressed, meaning only part of DNA is translated into proteins. The cell therefore only makes those proteins that it requires to carry out its specialised function. These proteins include those required to carry out specialised processes like respiration and membrane synthesis. Although it is still capable of making all the other proteins, these are not needed and so it would be wasteful to produce them. In order to conserve energy and resources, a variety of stimuli ensure the genes for these other proteins aren’t expressed.
The ways in which genes are prevented from expressing themselves include:
Preventing transcription and so preventing the production of mRNA
Preventing translation
totipotent stem cells
found in early embryo and can differentiate into any type of cell.
the zygote is totipotent and as it divides, it cells develop into slightly more specialised cells called pluripotent stem cells
pluripotent stem cells
found in embryos and can differentiate into almost any type of cell
multipotent stem cell
found in adults and can differentiate into a limited number of specialised cells. usually develop into cells of a particular type
unipotent stem cells
can only differentiate into a single type of cell. are derived from multipotent cells and are made into adult tissue
induced pluripotent stem cells
iPS cells
produced from unipotent stem cells
body cells are genetically altered in the lab to make them acquire the characteristics of embryonic stem cells. involves inducing genes and transcriptional factors within the cell to express themselves
are not exact replicates of embryonic stem cells
are capable of self-renewal, so could divide indefinitely to provide a limitless supply
pluripotent in treating human disorders
can be used to regrow tissues that have been damaged in some way i.e. accident ( skin grafts for serious burn damage) or a result of disease (neuro-degenerative disease such as Parkinson’s)
effects of oestrogen on gene transcription
is lipid-soluble and so diffuses easily through the phospholipid portion of membrane
once inside the cytoplasm, oestrogen binds to a site on the receptor molecule of the transcriptional factor. (complementary shape)
by binding, oestrogen changes the shape of DNA binding site on the transcriptional factor, which can now bind to DNA
transcriptional factor can enter the nucleus through a nuclear pore and bind to a specific base sequence on DNA
combination of transcriptional factors with DNA stimulates transcription of the gene that makes up the portion of DNA
general principles in controlling expression of a gene by controlling transcription
for transcription to occur the gene is switched on by specific molecules that move from the cytoplasm into the nucleus. the molecule is called a transcriptional factor
each factor has a site that binds to a specific base sequence of DNA in the nucleus.
when binding, it causes the region of DNA to begin transcription
mRNA is produced and the information it carries is translated into a polypeptide
when gene isn’t expressed, the site on the factor that binds to DNA isnt active
as it is inactive, it cannot cause transcription
epigenetics
now believe environmental factors can cause heritable changes in gene function without chagning the base sequence of DNA
provides explanation as to how environmental influenences such as diet, stress, toxins ect can subtly alter the genetic inheritance of an organisms offspring
epigenome
DNA is wrapped around proteins called histones. both the DNA and histones are covered in chemicals called tags.
determines the shape of the DNA-histone complex
e.g. it keeps genes that are inactive in a tightly-packed arrangement and therefore ensures that it cant be read (epigenetic silencing). it unwraps active genes so DNA is exposed
is flexible as chemical tags respond to environmental changes
the accumulation of the signals it has received during its lifetime and so acts as a cellular memory
DNA- histone complex
association of histones with DNA is weak and so the DNA-histone complex is considerably less condensed. the DNA is accessible by transcriptional factors which can initiate production of mRNA
where assiation is stronger, DNA-histone complex is more condensed and so DNA is not accessible by transcriptional factors which cannot initiate production of mRNA
condensation of the complex therefore inhibits transcription.
can be brought about by decreased acetylation of histones or methylation of DNA
decreased acetylation of associated histones
acetylation is the process where an acetyl group is transferred to a molecule. the group donating the acetyl group is acetylcoenzyme A.
decreased acetylation increases the positive charges on histones and therefore increases their attraction to phosphate groups on DNA. the association between histones is therefore greater and the DNA is not accessible to transcriptional factors , which cannot initiate mRNA production from DNA
increased methylation of DNA
methylation is the addition of a methyl group
methyl group is added to cytosine and methylation normally inhibits the transcription of genes in 2 ways:
1. preventing the binding of transcriptional factors
2. attracting proteins that condense the DNA-histone complex making DNA inaccessible to transcriptional factors
epigenetics and inheritance
experiments on rats has shown female offspring who received good care when young, respond better to stress in later life and themselves nurture their offspring better
female offspring receiving low-quality care, nurture their offspring less well
good maternal behaviour in rats transmit epigenetic information into their offspring DNA without passing through gametes
epigenetics and disease
epigenetic changes are part of a normal development and health but is also responsible for certain diseases
can cause abnormal activation/silencing of genes
tissues that have less methylated DNA had higher than normal gene activity
sections of DNA near promoter regions that have high methylated DNA will cause typically active cells to turn off
don’t alter the sequence of bases but increases the likelihood of a mutation
increased methylation in active cells shut them off
epigenetics and treating diseases
therapy counteracts epigenetic changes
drugs inhibit enzymes involved (specifically targeted)
diagnostic tests help detect the early onset
effect of RNA interference on gene expression
double-stranded RNA is broken via an enzyme into siRNA
1/2 strands of siRNA combines with an enzyme
siRNA pairs with complementary base on mRNA
enzyme cuts mRNA into smaller section
siRNA guides the enzyme to mRNA by pairing up bases with complementary ones on a section of mRNA
once in position, enzyme cuts mRNA into smaller sections and is no longer capable of being translated into a polypeptide.
means the gene hasn’t been expressed
cancer
a group of diseases caused by damage to the genes that regulate mitosis and the cell cycle.
leads to unrestrained growth of cell and as a consequence, a group of abnormal cells (a tumour) develops and constantly expands in size
what are the characteristics of malignant tumours
grow to large size and rapidly
cell nucleus is often larger and appears darker due to DNA abundance
cells become de-differentiated
how can malignant tumours spread?
don’t produce adhesion molecules so tend to spread to other regions in a process called metastasis
not surrounded by a capsule and can grow finger-like projections into surrounding tissue
what is the effect like of malignant tumours?
more likely to be life-threatening as abnormal tumour tissues replace normal tissues
often have systematic effects such as weight loss and fatigue
how do you remove malignant tumours?
usually involves radiotherapy and/or chemotherapy as well as surgery
more frequently occur after surgery `
what are the characteristics of benign tumours
can grow to a large size but very slowly
the nucleus has a relatively normal appearance
cells are often well differentiated
why do benign tumours not spread?
has adhesion molecules that make them stick together so they remain within the tissue from which they are formed (primary tumours)
are surrounded by a capsule of dense tissue so remains a compact structure
what are the effects of benign tumours
less likely to be life-threatening but can still disrupt the functioning of vital organs
tend to have a localised effect on the body
how do you remove benign tumours
can usually be removed via surgery alone
rarely reoccur after surgery
what are oncogenes
are mutations of proto-oncogenes
what are proto-oncogenes?
stimulate a cell to divide when growth factors attach to a protein receptor on its cell-surface membrane
this activates genes that cause DNA to replicate.
if it mutates, it can become permanently activated
why can proto-oncogenes become permanently activated when mutated to an ocogene?
- the receptor protein on the cell-surface membrane can be permanently activated so cell division is always on
- oncogene may code for a growth factor that is then produced in excessive amounts
what is the difference between oncogenes and tumour suppressor genes
oncogenes cause cancer as a result of the activation of proto-oncogenes, tumour suppressor genes cause cancer when they are inactivated
how does hypermethylation cause cancer
- occurs in a specific region (promoter region) of tumour suppressor genes
- leads to the tumour suppressor gene being inactivated
- so, transcription of the promoter regions is inhibited
- so the tumour suppressor gene is silenced
- as it normally slows the rate of cell division, its inactivation leads to increased cell division
what is the link between breast cancer and oestrogen concentrations
oestrogen concentrations in fat cells in the breast is high post menopause. seems to trigger breast cancer
oestrogen activates a gene by releasing an inhibitor molecule that prevents transcription
if the gene it acts on is one that controls cell division and growth, it will be activated and its continued division can form a tumour
what is genome
all the genetic material in a cell
How do you determine the DNA base sequence of an organism
by using whole-genome shotgun (WGS) sequencing which involves researchers cutting the DNA into many small, easily sequenced sections and use a computer algorithms to align overlapping sections to assemble entire genomes
what is the proteome?
the proteins that genes code for
or
all the proteins produced in a single cell (cellular proteome) or organisms (complete proteome) at a given time under specified conditions
how do you determine the shape and proteome of simpler organisms?
how do you determine the shape and proteome of complex organisms?
what techniques have been developed to produce large quantities of pure proteins
to isolate genes, clone them and transfer them to into microorganisms, which are then grown to provide a factory for the continuous production of the desired protein
what is recombinant DNA
the DNA of 2 different organisms that has been combined in the way of isolation, cloning and transferring
the resulting organism is known as a transgenic or genetically modified organism (GMO)
why does the DNA function normally in another organism ?
the genetic code is the same in all organisms. it is universal and can be used by all living organisms.
the making of proteins is also universal as the mechanisms of translation and transcription are essentially the same in all living organisms
what are the stages of making a protein using gene transfer and cloning?
- isolation
- insertion
- transformation
- identification
- growth/cloning
