DP Biology HL D2.2 Gene Expression

DP Biology HL D2.2 Gene Expression - Full notes

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DP Biology HL | D2.2 Gene Expression

DP BIOLOGY · THEME D: CONTINUITY AND CHANGE

D2.2

Gene Expression

Full notes for HL · IB-style

Contents

1	Gene expression and the phenotype
2	Regulation of transcription: promoters and transcription factors
3	Epigenetics: DNA methylation and histone modification
4	Epigenetic inheritance and the environment
5	Measuring gene expression and the transcriptome
6	Monozygotic twins and imprinting
7	Gene expression defined
8	Transcription factors
9	Promoters and enhancers
10	mRNA degradation
11	Epigenetics
12	Epigenetic inheritance
13	Environment and gene expression
14	Monozygotic twin studies
15	Genomic imprinting
16	Lac operon (prokaryotic regulation)
17	Cell differentiation and gene expression
18	Hormones and gene expression
19	Mixed review: worked problems
20	Additional exam-style practice
21	Epigenetics and disease
22	Measuring gene expression
23	Practical: environmental effects on phenotype
24	Common misconceptions and links
25	Exam-style question with markscheme
26	Check your understanding
27	Summary and topic map

These are full teaching notes. Read each section in order, try the Think about it question before you read on, and do every Quick check before moving to the next section.

Before you start

Rate yourself on each statement now, and again after you've worked through the notes. Shade R (not yet), A (getting there) or G (confident).

I can…	R	A	G
explain how gene expression determines the phenotype of cells
explain how promoters and transcription factors regulate transcription
explain the effects of DNA methylation and histone modification
explain how environmental factors can change the epigenome
explain epigenetic inheritance, including evidence from twins and famine studies
distinguish genome, transcriptome and proteome

D2.2 is an Additional Higher Level (AHL) subtopic. It is studied by HL students only.

Guiding questions

How is gene expression controlled so that different cells with the same genes become different? How can the environment change which genes are expressed?

How this topic is examined

D2.2 is an HL-only subtopic, examined through explanations of transcription regulation and epigenetics, and data-based questions on methylation, twins and the Dutch Hunger Winter.

Be precise: epigenetic changes alter gene expression without changing the base sequence.

Command term	What the examiner wants
State / Identify	a brief answer with no explanation needed
Outline	a brief account or summary
Describe	a detailed account, including trends or features, without reasons
Explain	a detailed account including causes, reasons or mechanisms
Distinguish / Compare and contrast	give the differences (and similarities), point by point
Calculate	a numerical answer with working and units
Deduce / Suggest	reach a conclusion from data; propose a reasonable explanation
Evaluate / Discuss	weigh strengths and limitations and reach a judgement

How to use these notes

Each section teaches one part of the syllabus in full. You'll see these boxes throughout; each has one job:

Box	What it's for
Think about it	a question to get you thinking before a section; the answer comes in the section
Key point	the one idea you must not forget
Common mistake	an error examiners see every year, and how to avoid it
In the real world	where the biology shows up outside the classroom
Try this	something quick you can do yourself to test the idea
Worked example	full solutions with IB-style marks (M1 method, A1 answer, R1 reasoning)
Quick check	short questions to test yourself at the end of each section

1 Gene expression and the phenotype

Which genes are switched on determines what a cell is.

Think about it

A liver cell and a neuron contain identical DNA. What makes one store glycogen and the other carry nerve impulses?

Gene expression is the process by which information in a gene is used to make a functional product, usually a protein, through transcription and translation. Cells express only a fraction of their genes. The pattern of gene expression determines the phenotype of the cell: its structure and function.

Gene expression is regulated at several levels: transcription (the main control point), RNA processing (splicing), translation, and protein modification and breakdown. Regulation allows cells to differentiate (B2.3) and to respond to changes in their environment.

2 Regulation of transcription: promoters and transcription factors

Switches that turn genes on and off.

Each gene has a promoter, a sequence of DNA just before the coding region, where RNA polymerase binds to start transcription. Transcription is controlled by transcription factors: proteins that bind to specific DNA sequences in or near the promoter. Some help RNA polymerase bind and increase transcription (activators); others block binding (repressors).

Transcription factors can be activated by signals. For example, steroid hormones such as oestradiol bind to receptor proteins, and the hormone-receptor complex acts as a transcription factor (C2.1). Sequences further away, called enhancers, can also bind activators and increase transcription.

In prokaryotes, groups of genes for one pathway are often controlled together in an operon. In the lac operon of E. coli, the genes for lactose metabolism are transcribed only when lactose is present: lactose inactivates a repressor protein that otherwise blocks transcription. This prevents wasting energy making enzymes when they are not needed.

Figure 1. Control of transcription by transcription factors.

Quick check

1. What is a promoter?

2. What are transcription factors?

Answers: 1. DNA sequence where RNA polymerase binds to start transcription 2. proteins that bind DNA to increase or decrease transcription

3 Epigenetics: DNA methylation and histone modification

Chemical tags change expression without changing sequence.

Epigenetics is the study of heritable changes in gene expression that do not involve changes in the base sequence of DNA. The collection of epigenetic tags in a cell is its epigenome. Two main mechanisms are involved.

DNA methylation: methyl groups (–CH₃) are added to cytosine bases, usually where C is followed by G (CpG sites), often in promoters. Methylation generally reduces transcription, by preventing transcription factors binding and by attracting proteins that compact chromatin. Genes that are not needed in a cell type are often heavily methylated.

Histone modification: chemical groups can be added to the tails of histone proteins. Acetylation of histones loosens the binding between histones and DNA, opening up the chromatin so transcription factors and RNA polymerase can reach the genes: transcription increases. Removal of acetyl groups and some kinds of methylation of histones make chromatin more tightly packed, so transcription decreases.

Modification	Effect on chromatin	Effect on transcription
DNA methylation (cytosine)	more condensed	decreases
Histone acetylation	less condensed (open)	increases
Histone deacetylation	more condensed	decreases

Key point

Epigenetic marks change how accessible genes are, so they change expression without altering the DNA sequence.

Quick check

1. Define epigenetics.

2. How does histone acetylation affect transcription?

Answers: 1. heritable changes in gene expression without changes in base sequence 2. loosens chromatin, increasing transcription

4 Epigenetic inheritance and the environment

Experiences can leave marks on the epigenome.

Epigenetic tags are copied when cells divide, so a differentiated cell's pattern of expression is passed to its daughter cells. Most tags are erased when gametes form and in the early embryo, but some are retained and passed to offspring: epigenetic inheritance.

Environmental factors can change the epigenome: diet, stress, smoking, pollution, temperature and drugs. The Dutch Hunger Winter (1944-45): a severe famine in the Netherlands during the Second World War. People who were in the womb during the famine had, decades later, higher rates of obesity, heart disease and diabetes, and differences in methylation of genes involved in growth and metabolism (such as IGF2). Some effects were reported even in their children.

Plants also show epigenetic responses: the flowering of many plants after a long cold period (vernalization) depends on epigenetic silencing of a gene that inhibits flowering.

In the real world

Agouti mice show the effect of diet on the epigenome. Genetically identical mice can be yellow and obese or brown and lean, depending on how heavily one gene is methylated, which in turn depends on the mother's diet during pregnancy.

Quick check

1. What is epigenetic inheritance?

2. What did the Dutch Hunger Winter study show?

Answers: 1. passing epigenetic tags to offspring 2. prenatal famine linked to later disease and altered methylation

5 Measuring gene expression and the transcriptome

Which genes are active in a cell right now?

The genome is the complete set of DNA of an organism; it is the same in almost every cell. The transcriptome is the complete set of RNA molecules transcribed in a cell at a particular time; it differs between cell types and changes with conditions. The proteome is the complete set of proteins (B1.2).

Gene expression can be measured by detecting mRNA, for example using microarrays or RNA sequencing, which show which genes are active and how strongly. Comparing transcriptomes of healthy and diseased tissue (such as tumours) helps identify genes involved in disease. Researchers can also use tumour markers: proteins produced at high levels by some cancers.

Term	Meaning	Same in all cells?
Genome	all DNA of an organism	yes (almost)
Transcriptome	all RNA transcribed in a cell at one time	no
Proteome	all proteins produced	no

6 Monozygotic twins and imprinting

Identical genes, diverging epigenomes.

Monozygotic (identical) twins develop from a single zygote and have identical genomes. Studies show that young twins have very similar epigenomes, but differences increase with age, especially when twins have lived apart with different lifestyles. This may explain why identical twins can differ in diseases such as diabetes, schizophrenia or cancer.

Genomic imprinting is a form of epigenetic marking in which certain genes are expressed only from the allele inherited from one parent; the other copy is silenced by methylation. For example, the IGF2 gene is expressed from the paternal copy only. Faulty imprinting causes disorders such as Prader-Willi and Angelman syndromes.

Figure 2. Epigenetic differences between monozygotic twins increase with age.

Quick check

1. Why do identical twins become more different with age?

2. What is genomic imprinting?

Answers: 1. epigenomes diverge with different environments 2. expression of a gene from only one parent's allele

7 Gene expression defined

From gene to phenotype.

Gene expression is the process by which information in a gene is used to make a product (protein or functional RNA), affecting the phenotype. It is regulated at transcription, mRNA processing, translation and post-translation.

WORKED EXAMPLE 1 Levels (standard)

List three levels at which gene expression can be regulated.

Solution

Transcription; mRNA processing/degradationA1

Translation; post-translational modificationA1

8 Transcription factors

Switching genes on and off.

Transcription factors are proteins that bind to specific DNA sequences (promoters or enhancers) to promote or inhibit the binding of RNA polymerase. Different cell types have different transcription factors, so they express different genes.

WORKED EXAMPLE 2 Activator (standard)

Explain how a transcription factor increases expression of a gene.

Solution

Binds a specific DNA sequence near the geneR1

Helps RNA polymerase bind the promoterR1

9 Promoters and enhancers

Control sequences.

The promoter is the region where RNA polymerase binds to start transcription. Enhancers are DNA sequences, sometimes far from the gene, that bind activator proteins and increase transcription; silencers reduce it.

Quick check

1. Distinguish a promoter and an enhancer.

Answers: 1. promoter: RNA polymerase binding site next to gene; enhancer: distant sequence binding activators

10 mRNA degradation

How long a message lasts.

The lifetime of mRNA in the cytoplasm controls how much protein is made. Some mRNAs are degraded within minutes, others last hours. MicroRNAs can bind mRNA and trigger its degradation or block translation.

WORKED EXAMPLE 3 miRNA (standard)

Explain how microRNA reduces gene expression.

Solution

Binds complementary sequence on mRNAR1

Causes degradation or blocks translationR1

11 Epigenetics

Heritable changes without changing DNA sequence.

Epigenetic modifications change gene expression without altering the base sequence: DNA methylation (adding methyl groups to cytosine, usually silencing genes) and histone modification (acetylation loosens chromatin, increasing transcription; deacetylation tightens it).

WORKED EXAMPLE 4 Histone acetylation (exam level)

Explain how histone acetylation affects transcription.

Solution

Acetylation reduces positive charge on histonesR1

DNA less tightly bound: more accessible to RNA polymeraseR1

12 Epigenetic inheritance

Passed between cell generations.

Methylation patterns are copied when cells divide, so differentiated cells pass on their pattern of gene expression. Some epigenetic marks can be inherited between generations, though most are reset in gametes.

Quick check

1. Why do daughter cells of a liver cell remain liver cells?

Answers: 1. methylation patterns are copied during replication

13 Environment and gene expression

Nature and nurture.

Environmental factors can change gene expression: temperature affects fur colour in Himalayan rabbits (an enzyme active only in cooler extremities); diet and stress alter methylation; pollution and smoking change gene expression in lung cells.

WORKED EXAMPLE 5 Himalayan rabbit (standard)

Explain why Himalayan rabbits have dark ears and paws.

Solution

Enzyme for pigment is active only at lower temperaturesR1

Extremities are coolerR1

14 Monozygotic twin studies

Same genes, different expression.

Identical twins have the same DNA, but their epigenetic profiles diverge with age, especially if they live in different environments. Differences in diseases between twins show the role of environment and epigenetics.

In the real world

Studies show that older identical twins have more different DNA methylation patterns than younger twins, especially if they have lived apart.

Quick check

1. Why are twin studies useful in studying gene expression?

Answers: 1. genetic differences are controlled, so differences reflect environment and epigenetics

15 Genomic imprinting

Parent-of-origin effects.

Some genes are expressed only from the allele inherited from one parent; the other is silenced by methylation. Errors in imprinting cause disorders such as Prader–Willi and Angelman syndromes.

Quick check

1. What is genomic imprinting?

Answers: 1. expression of a gene depending on which parent it came from

16 Lac operon (prokaryotic regulation)

Inducible genes.

In E. coli, genes for lactose metabolism are switched on only when lactose is present. A repressor protein binds the operator, blocking transcription; lactose binds the repressor, changing its shape so it releases the operator, and the genes are transcribed.

WORKED EXAMPLE 6 Lac operon (exam level)

Explain how the presence of lactose switches on lactose-digesting genes.

Solution

Lactose binds repressorR1

Repressor no longer binds operator; RNA polymerase transcribes genesR1

17 Cell differentiation and gene expression

Same genome, different cells.

All somatic cells contain the same genes, but different combinations are expressed. Master regulatory genes (such as MyoD for muscle) switch on cascades of genes, giving specialized cell types.

Quick check

1. Why can a skin cell not normally produce insulin?

Answers: 1. insulin gene is not expressed (silenced) in skin cells

18 Hormones and gene expression

Signals reaching the nucleus.

Steroid hormones enter cells and, bound to receptors, act as transcription factors. For example, oestradiol increases transcription of genes in the uterine lining. Thyroxine regulates metabolism genes.

Quick check

1. How does a steroid hormone change gene expression?

Answers: 1. hormone–receptor complex binds DNA and regulates transcription

19 Mixed review: worked problems

Bringing the ideas together.

WORKED EXAMPLE 7 Mixed problem (exam level)

Outline how DNA methylation and histone acetylation affect gene expression.

Solution

Methylation of cytosine (in promoters) usually silences genesR1

Acetylation loosens chromatin, increasing transcriptionR1

20 Additional exam-style practice

Paper 1 and Paper 2.

WORKED EXAMPLE 8 Paper 1 question (standard)

Which usually increases transcription? A. DNA methylation B. histone deacetylation C. histone acetylation D. repressor binding

Solution

CA1

WORKED EXAMPLE 9 Paper 2 question (exam level)

Explain how the environment can influence gene expression.

Solution

Factors such as temperature, diet, stressR1

Alter methylation or transcription factor activity; change phenotypeR1

21 Epigenetics and disease

Cancer and beyond.

Abnormal methylation can silence tumour suppressor genes, contributing to cancer. Some cancer drugs inhibit DNA methyltransferases or histone deacetylases to reactivate silenced genes.

Quick check

1. How could inhibiting methylation help treat cancer?

Answers: 1. reactivates silenced tumour suppressor genes

22 Measuring gene expression

Microarrays and RNA sequencing.

Gene expression is measured by detecting mRNA: microarrays and RNA sequencing show which genes are active in a sample and how strongly, allowing comparison between tissues or diseased and healthy cells.

Quick check

1. Why is mRNA measured to study gene expression?

Answers: 1. its presence shows a gene is being transcribed

23 Practical: environmental effects on phenotype

Light and plant colour.

Seedlings grown in darkness are pale and tall (etiolated) because chlorophyll synthesis genes are not expressed without light. This shows the environment affecting gene expression.

WORKED EXAMPLE 10 Explaining (standard)

Explain why dark-grown seedlings are yellow.

Solution

Light needed to activate genes for chlorophyll synthesisR1

Try this

Grow cress seeds in light and in darkness for a week. Compare colour, height and leaf size.

24 Common misconceptions and links

Students often think…	Actually…
epigenetic changes alter the DNA sequence	they alter expression, not sequence
methylation always increases expression	DNA methylation usually decreases it
the transcriptome is the same in every cell	it varies with cell type and conditions

How D2.2 connects to the rest of the course

Topic	Connection
D1.2 Protein synthesis	transcription and splicing
B2.3 Cell specialization	differentiation
C2.1 Signalling (HL)	steroid hormones as transcription factors
A1.2 Nucleic acids (HL)	nucleosomes and histones
D2.1 Cancer (HL)	gene expression in tumours

25 Exam-style question with markscheme

Try this under exam conditions (about 15 minutes) before reading the markscheme.

Figure 3. Methylation differences between identical twins at two ages.

(a) Describe the trend shown. [1]

(b) Suggest a reason for this trend. [2]

(d) Explain how histone acetylation affects gene expression. [2]

(e) Outline the evidence for epigenetic inheritance from the Dutch Hunger Winter. [2]

Markscheme

Part	Answer	Marks
(a)	differences increase with age	A1
(b)	different environments / lifestyles	R1
	alter epigenetic tags over time	R1
(c)	methyl groups added to cytosine	R1
	prevents transcription factor binding / condenses chromatin	R1
	reduces transcription	R1
(d)	loosens histone-DNA binding	R1
	increases access and transcription	R1
(e)	prenatal famine exposure	R1
	later disease and altered methylation, some in next generation	R1

Examiner's comments. In (c), weaker answers said methylation 'deletes the gene'. The gene is silenced, not removed.

26 Check your understanding

Section A: multiple choice

1. A transcription factor

A. binds DNA to regulate transcription B. translates mRNA C. methylates histones only D. is an RNA molecule

2. DNA methylation usually

A. increases transcription B. changes the base sequence C. reduces transcription D. removes genes

3. Histone acetylation

A. condenses chromatin B. loosens chromatin C. stops all transcription D. methylates DNA

4. The transcriptome is

A. all DNA B. all proteins C. all genes D. all RNA transcribed in a cell

5. Epigenetic differences between identical twins

A. decrease with age B. increase with age C. are absent D. are only genetic

6. In the lac operon, lactose

A. inactivates the repressor B. activates the repressor C. is the promoter D. is a transcription factor

Section B: structured

7. Explain how gene expression is regulated by transcription factors. [3]

8. Distinguish genome, transcriptome and proteome. [3]

9. Explain how the environment can affect gene expression. [4]

Answers

1. A 2. C 3. B 4. D 5. B 6. A

7. Bind promoter/enhancer; activators recruit RNA polymerase; repressors block; signals activate factors.

8. Genome: all DNA; transcriptome: RNA expressed at a time; proteome: proteins; last two vary.

9. Diet, stress, toxins change methylation and histone marks; e.g. Dutch Hunger Winter, agouti mice.

27 Summary and topic map

Idea	Remember
Gene expression	using a gene to make a product; determines phenotype
Transcription control	promoters, transcription factors, enhancers; lac operon
Epigenetics	changes in expression without sequence change
Methylation / acetylation	methylation silences; acetylation activates
Environment	diet, stress; Dutch Hunger Winter
Genome vs transcriptome	constant vs variable
Twins and imprinting	epigenomes diverge; parent-specific expression

Before the exam, make sure you…

•state that epigenetics does not change the sequence
•link each modification to its effect on chromatin
•use named examples
•distinguish genome, transcriptome and proteome

Gene Expression on one page

Cover this page with a sheet of paper and try to rebuild it from memory. Whatever you can't recall is what to revise next.

Figure 4. Topic map for Gene Expression.

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