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Control of Gene Expression

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Control of Gene Expression

All living cells within an organism contain the same genome, but why does each cell function differently from others? It is because the level of gene expression in different cells is controlled. Your skin cells are different from your hair cells, and your muscle cells are different from your cardiac cells because of the control of gene expression.

By controlling what genes are expressed, we can regulate the metabolic activities of different cells. This is because genes encode for proteins which, in turn, determine the function of a cell. As a result, cells become specialized to perform specific functions. This is why regulating gene expression is highly important because, without it, we wouldn't have specialized cells.

But first off, we need to have cells that have the ability to specialize into a large range of cells. These are called stem cells.

Stem cells

Stem cells are defined as unspecialised cells that divide indefinitely by mitosis and differentiate into many cell types. There are three classes:

Totipotent stem cells are present during the zygote stage and have the ability to differentiate into all cell types, including extra-embryonic cells (like the placenta). As you make your way down the list above, the range of differentiation decreases. When these cells become specialized, they can no longer become any other type of cell.

The fact that specialised cells no longer divide continuously is a good thing! It means they can efficiently perform their metabolic activities.

Control of Gene Expression

The regulation of gene expression begins before transcription, the first stage of protein synthesis. Regulatory proteins called transcription factors dictate which genes are expressed (turned 'on') and which genes are not expressed (turned 'off'). The diagram below illustrates the binding of a transcription factor to DNA. This process is tightly controlled so that specific messenger RNA (mRNA) molecules are produced, and therefore only specific proteins are produced.

Another type of gene expression regulation that occurs at the transcriptional level includes the alteration of the DNA-histone complex. This type is especially fascinating because the base sequence of DNA is not changed, and yet it still has the ability to direct which genes are expressed. This is called epigenetics.

Epigenetics

Epigenetics is the study of DNA and histone modifications to control gene expression. These modifications are heritable and are not caused by any changes to the base sequence of DNA. Modifications include DNA methylation and histone acetylation, illustrated in the diagram below. This has the effect of either condensing or loosening the DNA-histone complex. The pattern of modifications is called the epigenome.

Gene expression is tightly regulated, and for good reason. If the wrong genes are expressed or silenced, genetic diseases can arise. Cancer is a disease that is characterized by the uncontrollable proliferation of cells, and in some cases, the cause has an epigenetic origin.

Translational control of Gene Expression

Before translation occurs, additional changes to the mRNA molecule can occur. This can include mRNA splicing which is the removal of introns (non-coding DNA) from the molecule.

Even after translation, the polypeptide can be modified even further, such as the addition of chemical groups. A great example of this is the addition of a phosphate group to a polypeptide, catalysed by protein kinases. This addition can alter the folding of a protein and therefore change the protein function.

mRNA splicing occurs only in eukaryotic cells as their genome includes both introns and exons. Prokaryotic genomes contain only introns so mRNA splicing is unnecessary.

Genome projects and technology

The sequencing of a genome maps out of the complete set of genetic information contained within an organism. For example, the Human Genome Project (1990-2003) was a collaborative effort to determine all the genes in our cells. But this was no easy endeavour. The project used technologies like whole-genome shotgun (WGS) sequencing, and from this came other advances. These include DNA hybridization, which is used to locate specific alleles of a gene and genetic fingerprinting. These technological advances have wide applications in disease treatment and forensic science.

Control of Gene Expression - Key takeaways

  • All living cells contain the same genome, but specialized cells express specific genes.
  • Transcriptional control of gene expression includes transcription factors and epigenetic modifications.
  • Epigenetics is the study of DNA and histone modifications to control gene expression. This does not include changes to the base sequence of DNA.
  • Translational control of gene expression includes the addition of chemical groups to polypeptides, such as phosphate groups.
  • DNA technologies, such as DNA hybridization, emerged from genetic studies and are now widely used in medical and forensic applications.

Frequently Asked Questions about Control of Gene Expression

The control of gene expression is important as it leads to the creation of specialised cells. Also, it determines what proteins are being produced in a cell.

Epigenetic control describes modifications to DNA and histones to regulate gene expression. These modifications are heritable and are therefore passed down generations and do not include changes to the base sequence of DNA.

Controlling the genes expressed in a cell means controlling what proteins are being synthesised. Proteins dictate the function of a cell, and therefore the expression of particular genes will result in a cell performing a particular function. This leads to a specialised cell.

The timing of gene expression is controlled by proteins called transcription factors. These are regulatory proteins that bind to genes to activate their expression or silence their expression. They bind to genes to produce the required proteins when it is needed.

The control of gene expression can happen at a transcriptional and translational level. At a transcriptional level, transcription factors can activate or silence specific genes. DNA and histones can be modified to result in a tightly packed or loosely packed DNA-histone complex. At a translational level, chemical groups can be added to the polypeptide to affect the folding and function of a protein.

Final Control of Gene Expression Quiz

Question

What are stem cells?

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Stem cells are unspecialised cells that indefinitely divide by mitosis and can differentiate into many cell types.

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What are the different stem cell types?


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Totipotent, pluripotent and multipotent stem cells.

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Proteins called _______ _________ determine which genes are switched on or off. 


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Transcription factors.

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Describe the epigenetic control of genes.


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Answer

The heritable modification of DNA and histones to control gene expression. There is no change to the base sequence of DNA.

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What structure is modified in epigenetics?


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The DNA-histone complex.

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Question

State a type of gene expression regulation that occurs before translation.


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mRNA splicing (in eukaryotic cells).

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Identify a type of gene expression regulation that occurs after translation. 


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The addition of a chemical group, like a phosphate group.

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What protein type catalyses the addition of a phosphate group to a polypeptide?


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Protein kinases.

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Question

State two examples of DNA technologies that have applications to medical and forensic science. 


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Answer

DNA hybridization. 

Genetic fingerprinting.

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Identify one DNA technology that was used in the Human Genome Project. 


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Answer

Whole-genome shotgun (WGS) sequencing.

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 How would increased methylation of DNA affect gene transcription?

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Answer

Addition of a CH3 group to cytosine bases prevents transcription factors from binding. Therefore gene transcription is inhibited.

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What is the correlation coefficient used for?


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Answer

To determine whether two variables correlate

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Question

What is the general appearance of a tumour cell?

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  • They have a larger and darker nucleus compared to other cells. 

  • They may have more than one nucleus.

  • They have an irregular shape.

  • They don't produce all proteins needed to function correctly

  • They have different antigens on their surface compared to normal cells.

  • They don't respond to the body's regulating processes.

  • They divide by mitosis more frequently than normal cells.

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Metastasis definition

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When a piece of tumour cell breaks off and spreads to another part of the body.

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What are cohort studies?

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Cohort studies follow a group over time to see who develops diseases and who doesn't. Exposures to risk factors are recorded over time.

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What factors affect the risk of developing cancer?

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Answer

  • Diet - There is strong evidence that suggests that a good diet rich in fruit, veg and fibre reduces the risk of getting cancer.
  • Obesity - Linked to diet, being overweight also increases the risk of cancer. 
  • Exercise - People who are more physically active are at a lower risk than those who do little or no exercise.
  • Sunlight - The more ultraviolet light someone is exposed to, the more at risk they are.
  • Smoking - Both smokers and those who breathe in tobacco passively are at increased risk of cancer.

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Correlation definition

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A correlation is the statistical measure of the relationship between two variables. It is best demonstrated in variables with a linear relationship between each other.

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What are cohort studies?


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Cohort studies follow a group over time to see who develops diseases and who doesn't. Exposures to risk factors are recorded over time.

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Benign definition

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A mass of cells that doesn’t invade neighbouring tissue or metastasise

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How does a malignant tumour form?

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  • Malignant cells develop, divide and invade normal tissues.

  • Some of the cells detach and spread through the blood and lymph vessels.

  • The malignant cells can squeeze through the capillary wall.

  • They then divide, producing a secondary tumour in a different location to the original tumour.

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What is a disadvantage of cohort studies?


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Cohort studies are very time consuming and expensive in comparison to case studies. This is because it takes people a long time to develop diseases.

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Malignant definition


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Tumours that spread through the body and cause cancer.

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What causes cancers to arise?


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Uncontrolled cell division

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How are mutations kept under control?


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  1. Picked up by various regulatory functions in the cell cycle
  2. Early cell death (apoptosis)
  3. Being destroyed by the bodies immune system

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What are cohort studies?


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Answer

Cohort studies follow a group over time to see who develops diseases and who doesn't. Exposures to risk factors are recorded over time.

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Question

Compare and contrast benign and malignant tumours.


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Answer

Both benign and malignant tumours can grow large however benign tumours grow slowly, and have more localised effects whereas malignant tumours grow rapidly and have systemic effects. Benign tumours can usually be removed by surgery alone whereas malignant tumours often require radiotherapy or chemotherapy as well. They are also more likely to be life-threatening than benign tumours and have a high rate of recurrence. Benign tumours are often surrounded by a capsule and don't metastasise whereas malignant tumours don't have a capsule and do metastasise.

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Question

What is the correlation coefficient used for?


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Answer

To determine whether too variables correlate. 

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What are case studies?

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Answer

A group of people who have the disease to be studied are compared with a group of individuals who do not have the disease.

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What is the aim of preventative medicine?

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Answer

To stop an illness before it starts and takes a holistic approach by focusing on the many factors that play a role in health. This includes maintaining a healthy lifestyle.

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What is a genome?

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Answer

The complete set of genetic material in an organism.

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What is proteome?

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The complete set of proteins an organism/cell can make at given conditions.

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What is HPG?


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HPG is the human genome project and involved sequencing the whole human genome.

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What is genome sequencing?

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Identifying the DNA base sequence of an organism genome. It allows determining the amino acid sequence of the polypeptides encoded by that DNA.

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How is PCR used in genome sequencing?


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Answer

Automated DNA sequencing methods require large quantities of DNA. PCR allows amplifying the DNA samples taken from the organism.

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Question

What is dideoxyribonucleotide?


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Answer

Dideoxyribonucleotide is a special type of nucleotide that differs from normal deoxyribonucleotides in that it contains an additional hydrogen instead of a hydroxyl group on carbon number.

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What is the role of dideoxyribonucleotide in DNA sequencing?


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Dideoxyribonucleotide acts as an inhibitor of chain elongation and once incorporated, terminates further nucleotide addition to the DNA strands.

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Why are dideoxyribonucleotides fluorescently labelled in DNA sequencing?


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The 4 different dideoxyribonucleotides (A, G, T, and C) are tagged with different fluorescent labels giving each a distinct colour. Since dideoxyribonucleotides will be incorporated into the growing DNA strands randomly, the result would be new DNA fragments of various lengths and sizes that have the same point of origin (all starting from the primer) but end with a fluorescently labelled dideoxyribonucleotides. The colour of the terminal dideoxyribonucleotide help identifies the nature of the terminal DNA base.

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Question

What is the role of gel electrophoresis in DNA sequencing?


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Answer

The obtained fragments from the previous step on then run on gel electrophoresis which separates the strands according to their length. Due to the random nature of the last step, there will be strands present that are 1 nucleotide in size, 2 nucleotides in size, 3 nucleotides in size …… n nucleotide in size and they all end with a fluorescently labelled DdNTP. Therefore, the pattern of colour created by the fluorescent tags would tell us the DNA sequence.

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Question

Name some of the medical applications of identifying simple organisms’ proteome:


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Identifying antigenic proteins that are located on the surface of a pathogenic bacteria can be used in vaccines against diseases that are caused by those pathogens.

After knowing the sequence of these antigens, they can be manufactured in large quantities and then administered to people in appropriate doses. The body’s immune system would then respond against the antigen and create antibodies and memory cells. When encountered with the pathogen carrying this antigen, the memory cells would then mount a secondary immune response protecting the body from the infection.

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Name some of the non-medical applications of identifying simple organisms’ proteome:

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Answer

The proteome of simple organisms gives us an insight into the biochemistry of the reactions that occur within them. Some of these organisms are used for manufacturing biofuels. Furthermore, organisms with the ability to withstand extreme and toxic conditions can be used for removing pollutants from the environment.

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Why is determining the genome and proteome of simple organisms relatively easy?


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Answer

Prokaryotic DNA is much smaller than eukaryotic DNA. Prokaryotic DNA is not associated with histone proteins. There are no non-coding DNA sequences within the genome of prokaryotes. Eukaryotic DNA however contains vast portions of non-coding sequences.

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When was HPG completed?


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Answer

In 2003

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What is the main challenge in sequencing the genome of complex organisms?


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Answer

The main challenge with complex organisms is determining the proteome. This is because the eukaryotic DNA contains large portions of non-coding DNA. In humans, for example, 98.5% of the genome is thought to be non-coding and so do not contribute towards the proteome.

Another obstacle is whose genome to be used for sequencing since all individuals except identical twins have different genomes.

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Question

What was the main aim behind HPG?


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Answer

The Human Genome Project (HGP) was an international scientific research project aimed at defining the base pairs sequences within the human DNA, as well as identifying and mapping all of the human genome's genes with respect to their position as well as their function.

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How could epigenetic changes affect humans?

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Answer

They could cause disease, either by inhibiting or activating a gene.

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What effect do different genes in a cell being expressed have?


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Answer

Different proteins are made and these proteins modify the cell.

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Question

Describe the process of RNA interference.


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Answer

RNA molecules inhibit gene expression, by destroying mRNA so that it cannot be translated.

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Why does the structure and function of different cells vary in an organism?


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Answer

Not all the genes in a cell are expressed.

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Question

Describe RNA interference using siRNA.


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Answer

mRNA leaves the nucleus once it has been transcribed and enters the cytoplasm.

  • Double-stranded RNA cut using enzymes.

  • Each small section is called siRNA.

  • siRNA has a specific base sequence that is complementary to the target mRNA.

  • One strand of the siRNA binds to a protein (RISC) which then acts as an enzyme. 

  • The siRNA can now bind to the mRNA molecule by complementary base pairing.

  • The mRNAs phosphodiester bonds are hydrolysed.

  • The mRNA can no longer be used in translation and is broken down by the nuclease enzyme. 

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Question

What is recombinant DNA?

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Answer

DNA is created by combining two or more DNA molecules from different origins.

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