6.1 - cellular control

Gene mutation

A change in the DNA base sequence

How do mutations occur?

They happen if DNA is misread during DNA replication

Three types of gene mutations

substitution, deletion and insertion

substitution

One base is replaced by another. 

Deletion

One base is removed from the sequence

Insertion

One base is added into the sequence

How may mutations affect a gene?

They may change the amino acid sequence coded for by the gene. This will lead to a different polypeptide and potentially a different tertiary structure.

How could a mutation affect an enzyme?

it could change the shape of the active site, and stop it from forming an enzyme-substrate complex.

Why might a substitution not have any effect on the amino acid sequence?

Because of the degenerate nature of the genetic code. Many amino acids are coded for by more than one triplet.

frameshift

a type of gene mutation caused by the insertion or deletion of one or two nucleotides in a DNA sequence

why are deletions more likely to change the amino acid sequence?

They cause a frameshift

transcription factors

proteins that bind to specific DNA sequences to initiate the transcription of genes into mRNA

when is mRNA produced?

during transcription

What happens after transcription?

mRNA that is produced during transcription then carries the genetic code from DNA to ribosomes, allowing the production of proteins

what happens when a gene is ‘switched off’?

transcription factors cannot bind to DNA. This prevents the transcription process and so the synthesis of polypeptides.

Epigenetic regulation

changes in gene expression without altering the underlying DNA sequence, such as through histone modifications

how does histone modifications contribute to epigenetic regulation?

they can influence chromatin structure and gene activity by making DNA more or less accessible for transcription

Acetylation

• a modification that promotes transcription

• This process involves adding acetyl groups to histones, decreasing their positive charge and resulting in a looser DNA coil and increased transcription.

Phosphorylation

• a modification that promotes transcription

• Adding phosphate groups to histones reduces their positive charge, resulting in a looser DNA coil and increased transcription.

Methylation

• a modification that inhibits transcription

• This involves adding methyl groups to histones, increasing hydrophobic interactions and tightening the coiling of DNA, which reduces transcription.

Chromatin remodelling

the dynamic change in the structure of chromatin (DNA and proteins) to regulate gene expression, making DNA more or less accessible to transcription factors

two forms in which chromatin can exist

• heterochromatin

• euchromatin

heterochromatin

form of chromatin that is densely packed, making it difficult for RNA polymerase to access genes, thus preventing transcription

Euchromatin

a loosely packed form of chromatin that allows easy access for RNA polymerase, enabling active transcription of genes.

importance of chromatin remodelling

It allows cells to control which genes are active, influence cell function, and respond to environmental signals.

Operon

a cluster of genes controlled by a single promoter, allowing for coordinated expression

components of operons

• regulatory genes

• a promoter region

• an operator region

• structural genes

regulatory gene

encode proteins that regulate the expression of the structural genes.

A promoter region

the site where RNA polymerase binds to initiate transcription

An operator region

a sequence where regulatory proteins (like repressor proteins) can bind

Structural gene

code for proteins, typically enzymes

lac operon

a group of genes in the bacterium E.coli that control the metabolism of lactose, allowing them to use lactose as an energy source when glucose is scarce

what controls lac operon genes?

The promoter region

lacI

A regulatory gene of the lac operon that codes for a repressor protein that can inhibit and control the lac operon's activity

What does the gene lacZ code for?

β-galactosidase

function of β-galactosidase

Breaks down lactose into glucose and galactose

What does the gene lacY code for?

Lactose permease

function of lactose permease

transports lactose into the cell

What does the gene lacA code for?

Transacetylase

function of Transacetylase

Modifies lactose or its by-products

How does the lac operon function when lactose is absent?

1. The repressor protein binds to the operator region.

2. RNA polymerase is blocked from the promoter region.

3. RNA polymerase can't transcribe the structural genes.

4. The enzymes for lactose metabolism aren't produced.

How does the lac operon function when lactose is present?

1. Lactose binds to the repressor protein.

2. The repressor protein changes shape and is released from the operator region.

3. RNA polymerase can bind to the promoter region and initiate transcription.

4. RNA polymerase transcribes the structural genes, leading to the production of enzymes necessary for lactose metabolism.

How does glucose indirectly inhibit the lac operon?

via a signalling molecule, cyclic AMP (cAMP)

What happens when only lactose is present?

• cAMP levels increase, and cAMP binds to the cAMP receptor protein (CRP).

• The CRP-cAMP complex upregulates the transcription of the lac operon.

• Lactose metabolism is optimised.

What happens when both glucose and lactose are present?

• Glucose reduces cAMP levels.

• The CRP-cAMP complex cannot form.

• The lac operon's transcription is downregulated.

• Lactose metabolism enzymes are not produced.

What is pre-mRNA?

the initial RNA transcript produced during transcription that must be processed before translation.

What is RNA processing?

The modification of pre-mRNA to form mature mRNA that can be translated into a protein.

What are introns?

Non-coding regions of DNA that are transcribed into pre-mRNA but removed during RNA splicing.

What are exons?

Coding regions of DNA that remain after splicing and are joined together to form mature mRNA.

What happens during RNA splicing?

Introns are removed and exons are joined together to produce mature mRNA.

What is the purpose of the 5′ cap?

• Stabilises mRNA

• Protects it from degradation

• Helps the ribosome bind for translation

What is the purpose of the 3′ poly-A tail?

• Stabilises mRNA

• Delays degradation

• Helps the mRNA last longer in the cell

What is mature mRNA?

the processed mRNA containing only exons, with a 5′ cap and poly-A tail, ready for translation

What is RNA editing?

A process where nucleotides in mRNA are changed by substitution, addition, or deletion.

Why is RNA editing important?

It can change the protein produced, meaning different proteins can be made from the same mRNA.

What are the three main steps of RNA processing?

• Addition of a 5′ cap

• Addition of a 3′ poly-A tail

• Splicing (removal of introns)

translational control

the control of the rate at which translation occurs

factors that affect the rate of translation

• mRNA degradation rates

• inhibitory proteins

• initiation factors

how do mRNA degradation rates affect the rate of translation?

mRNA that degrades slowly is more stable and lasts longer, which can increase translation and protein synthesis

how do inhibitory proteins affect the rate of translation?

they can bind to mRNA, preventing it from attaching to ribosomes, which decreases translation and protein synthesis

how do initiation factors affect the rate of translation?

• Activated initiation factors help mRNA bind to ribosomes.

• This initiates translation and increases protein synthesis.

Protein kinases

a type of enzyme that can control many aspects of cellular activity, including protein modification

how do protein kinases work?

• Protein kinases add phosphate groups to proteins through phosphorylation.

• Phosphorylation changes the protein's tertiary structure and function.

• This often activates enzymes.

• The activity of protein kinases can be regulated by cyclic AMP (cAMP).

body plan

The basic structured arrangement of an organism's parts, which are determined by genetic and developmental factors

Homeobox genes

A group of regulatory genes with a conserved DNA sequence that guides the development of body plans

Homeobox sequence

A highly conserved DNA sequence found within homeobox genes that is crucial for the development of an organism's body plan

Hox gene

A subset of homeobox genes in animals, containing homeobox sequences essential for the correct positioning of body parts

how Hox genes control development

1. Homeobox sequences encode the homeodomain, the part of a protein that binds to DNA.

2. The homeodomain operates as a transcription factor.

3. It binds to DNA, switching developmental genes on or off.

4. This modifies the transcription of proteins necessary for the development of body plans.

homeodomain

the DNA binding part of a protein that is coded for by a hox gene

why are homeobox genes so conserved?

• A mutation would have large effects by altering the organism's body plan.

• Many other genes would also be affected by a mutation in a homeobox gene.

• Mutations are likely to be lethal and selected against.

aptosis

cell death

example of how aptosis and mitosis shape the body plan

mitosis causes embryonic fingers to grow as more cells are added lengthways, and the webbing between these fingers is removed through apoptosis

how hox genes are involved in mitosis and aptosis

they control the rate and location of cell division during growth and tissue formation, and they also control programmed cell death during development