Gene expression
🎯What you need to be able to do
- Explain gene expression as the mechanism by which genes affect phenotype.
- Explain regulation of transcription by promoters, enhancers and transcription factors.
- Explain control of mRNA degradation as a way of regulating translation.
- Define epigenesis, and distinguish the genome, transcriptome and proteome.
- Explain methylation of promoters and of histones as epigenetic tags.
- Explain epigenetic inheritance, and outline environmental effects on gene expression, including air pollution.
- Explain the consequences of removing most epigenetic tags from gametes, using tigons and ligers.
- Explain how monozygotic twin studies investigate environmental effects on gene expression.
- Give examples of a hormone and of a biochemical (lactose in bacteria) altering the pattern of gene expression.
📚The biology
Gene expression and phenotype
Gene expression is the mechanism by which the information in a gene has an effect on the phenotype. The most common route has three stages:
- Transcription of the gene into mRNA (D1.2);
- Translation of the mRNA into a polypeptide;
- The function of the protein product — for example an enzyme that catalyses a reaction producing a pigment, which gives a visible trait.
Expression can be controlled at each stage, so there are many points at which a cell can decide how much of a protein to make.
Regulating transcription
Transcription is controlled by proteins that bind to specific base sequences in DNA:
A sequence immediately before a gene, where RNA polymerase and general transcription factors bind to start transcription.
Sequences that can be some distance from the gene. When specific activator proteins bind to them, the DNA loops round so they interact with the promoter complex, increasing the rate of transcription. (Similar sequences called silencers bind repressors and reduce it.)
Proteins that bind to promoters or enhancers and help or block the binding of RNA polymerase. Which transcription factors a cell makes, and whether they are active, determines which genes it transcribes.
mRNA degradation
Once mRNA is made, the amount of protein produced depends on how long the mRNA survives in the cytoplasm before it is broken down by enzymes called nucleases. In human cells, mRNA may persist for anything from minutes to days. Controlling the rate of degradation is another way of regulating translation: mRNA for proteins needed only briefly, such as signalling proteins, is broken down quickly; mRNA for proteins needed constantly lasts longer.
Epigenesis
Epigenesis is the development of patterns of differentiation in the cells of a multicellular organism: as an embryo develops, cells take on different, stable patterns of gene expression and become different cell types. The key point is that DNA base sequences are not altered by epigenetic changes: the phenotype of the cell changes, but its genotype does not.
Genome, transcriptome and proteome
All the genetic information of an organism — the complete DNA sequence. The same in almost every cell of the body.
All the RNA molecules transcribed in a cell at a particular time. Differs between cell types and changes over time.
All the proteins produced by a cell (or organism) at a particular time. Differs between cells and changes with conditions.
No cell expresses all of its genes. The pattern of gene expression in a cell — its transcriptome and proteome — determines how it differentiates.
Epigenetic tags: methylation
Chemical groups attached to DNA or to histones act as epigenetic tags, marking genes to be expressed or silenced. Two examples:
- Methylation of the promoter. Methyl groups (–CH3) can be added to cytosine bases in DNA. When the promoter of a gene is heavily methylated, transcription factors and RNA polymerase cannot bind, so transcription is repressed and the gene downstream is not expressed.
- Methylation of histones. Methyl groups can also be added to certain amino acids in the histone proteins of nucleosomes. Depending on which amino acid is methylated, this can make the DNA pack more tightly (repressing transcription) or more loosely (activating it). (Details are not required.)
Epigenetic inheritance
Epigenetic tags can be copied when a cell divides. After DNA replication, enzymes recognize methylation on the old strand and add methyl groups to the matching positions on the new strand. Tags that remain in place during mitosis are passed to daughter cells, which is how a liver cell’s descendants stay liver cells. Occasionally, tags remain in place during meiosis and are passed to offspring. In both cases, a phenotypic change is inherited without any change to the nucleotide sequence of DNA.
Environmental effects on gene expression
The environment can change epigenetic tags and so alter gene expression. For example, exposure to air pollution, such as fine particulate matter from traffic, has been found to alter the pattern of methyl tags on DNA in blood cells, including at genes involved in inflammation and the response to oxidative stress. This may help to explain how pollution increases the risk of respiratory and cardiovascular disease. Diet, smoking, stress and temperature are other environmental factors shown to affect methylation.
Resetting tags in gametes: tigons and ligers
When sperm and eggs form, most, but not all, epigenetic tags are removed, so that the zygote can start development with a largely fresh pattern. The tags that remain can have striking consequences.
Some genes are imprinted: the copy from one parent is silenced by tags that survive into the embryo, so only the copy from the other parent is expressed. Some imprinted genes affect growth, with the father’s copies tending to promote growth of the offspring and the mother’s copies tending to restrain it.
- A liger (lion father × tiger mother) grows much larger than either parent. In lions, where females mate with several males, paternal growth-promoting genes are strongly expressed and maternal genes have evolved to counteract them. A tiger mother does not have that counterbalance, so the lion father’s growth-promoting imprinting goes unchecked.
- A tigon (tiger father × lion mother) is similar in size or smaller than its parents, because the lion mother’s growth-restraining imprinting is now combined with the tiger father’s weaker growth promotion.
Both hybrids receive the same two sets of genes. The difference in phenotype depends on which parent each set came from — an epigenetic, not a genetic, effect.
Monozygotic twin studies
Monozygotic (identical) twins develop from one zygote, so they have identical genomes. Any differences between them in phenotype must therefore come from the environment, including its effects on gene expression. Studies comparing twins have found that their patterns of DNA methylation are very similar at birth but become increasingly different with age, and more different in twins who have lived apart or had different lifestyles. This is evidence that the environment changes gene expression over a lifetime.
External factors that change gene expression
Oestradiol diffuses into target cells and binds to an intracellular receptor. The hormone–receptor complex binds to specific DNA sequences and acts as a transcription factor, switching on the transcription of particular genes, for example in cells of the uterus lining (C2.1).
The genes for enzymes that take up and digest lactose are grouped together in the lac operon. When lactose is absent, a repressor protein binds to the DNA next to the promoter, blocking RNA polymerase, so the genes are not transcribed. When lactose is present, a form of it binds to the repressor, changing its shape so it detaches from the DNA. RNA polymerase can now transcribe the genes, and the enzymes are made.
The lac operon makes biological sense: the bacterium makes lactose-digesting enzymes only when lactose is available, not wasting energy and amino acids on enzymes it cannot use.
✏️Worked example
(b) A mutation changes the repressor so that it can no longer bind to DNA. Predict the effect.
(c) A particular mRNA has a half-life of 2 hours in a cell (half of the molecules present are degraded every 2 hours). If transcription stops when 8000 molecules are present, calculate how many remain after 6 hours, and explain why controlling mRNA degradation regulates the amount of protein made.
(a) With no lactose, the repressor is bound to the DNA next to the promoter of the lac operon, blocking RNA polymerase, so the genes are not transcribed and the enzymes are not produced. When lactose is added, it binds to the repressor, changing its shape so that the repressor detaches from the DNA. RNA polymerase binds, the genes are transcribed and translated, and the enzymes are made, allowing lactose to be taken up and digested.
(b) The repressor could never block transcription, so the enzymes would be produced all the time, whether or not lactose was present. This wastes energy and amino acids when lactose is absent.
(c) 6 hours is three half-lives:
The rate of translation depends on how many mRNA molecules are available. An mRNA that is degraded quickly is translated for only a short time, so production of its protein stops soon after transcription stops; an mRNA that persists keeps being translated for hours or days. By changing how quickly nucleases break down an mRNA, a cell can control how much protein is made, and how quickly production responds to change.
📝Practise
Work through these on paper, then reveal the answer. All are HL only.
1. Distinguish between the genome, the transcriptome and the proteome of a cell.
2. Explain how enhancers and transcription factors regulate transcription.
3. Explain how methylation of DNA can silence a gene.
4. Explain what is meant by epigenetic inheritance.
5. Explain how studies of monozygotic twins provide evidence that the environment affects gene expression.
6. A liger is much larger than both of its parents, but a tigon is not. Explain this difference.
🔗Go deeper — other people’s work
These are external resources, not mine. If one stops working, tell me and everything above it on this page still stands.
- Learn.Genetics (University of Utah) — the Epigenetics module, including identical twins and imprinting.
- HHMI BioInteractive — animation of the lac operon.
- Nature Education, Scitable — articles on transcription factors, enhancers and DNA methylation.