Gene expression is the cellular process where information in a gene is used to make a functional product that affects the phenotype. Put simply: the DNA sequence isn’t the trait on its own. The cell has to use it.

Genotype is the set of genetic information carried by a cell or organism. Phenotype is the set of observable characteristics of a cell or organism, including biochemical functions as well as visible features. So phenotype isn’t just what you can see from the outside. Enzyme activity inside a liver cell counts too.

The usual path from gene to phenotype has three main stages. Transcription is the synthesis of an RNA molecule using one strand of DNA as a template. Translation is the synthesis of a polypeptide at a ribosome using the base sequence of mRNA. After that, the protein product has to do its job. For example, an enzyme is a globular protein that catalyses a chemical reaction by lowering the activation energy.

A gene that codes for an enzyme is a good example. When the gene is transcribed and translated, the enzyme may catalyse a reaction that changes cell chemistry. If that enzyme is missing or non-functional, the phenotype changes because the reaction no longer happens at the normal rate.

Gene expression doesn’t work like a simple light switch. A cell might express a gene strongly, weakly, briefly or continuously. Biologists can compare gene expression by measuring amounts of mRNA, protein or another gene product.

Cells don’t transcribe every gene all the time. Transcription regulation controls whether, when and how rapidly RNA is made from a gene. One major method is regulatory proteins binding to specific base sequences in DNA.

A promoter is a DNA sequence near a gene where RNA polymerase and associated proteins assemble to start transcription. In eukaryotes, some promoters include a short TATA-rich region, which helps position the transcription machinery. Think of the promoter as the “start here” region, although it still doesn’t explain by itself why a gene is active in one cell and silent in another.

Transcription factors are DNA-binding proteins that regulate transcription by binding to particular base sequences. Some help RNA polymerase bind or begin transcription; others make transcription less likely. Their binding sites vary between genes, so transcription factors allow selective control of individual genes or groups of genes.

An enhancer is a regulatory DNA sequence that increases transcription when an activator protein binds to it. Enhancers may be upstream, downstream or at a distance from the gene; DNA looping can bring the bound activator near the promoter. A repressor is a regulatory protein that decreases gene expression by preventing transcription or reducing its rate.

Here’s one answer to the linking question about inhibition in biology. Inhibition isn’t only about enzymes: gene expression can be inhibited when a repressor binds DNA or when an activator is absent. The effect is slower than blocking an enzyme already present, but it is powerful because it prevents production of the protein in the first place.

Transcription isn’t the only place where control happens. After an mRNA molecule has been made, the cell can still affect how much protein comes from it by controlling how long that mRNA lasts.

mRNA degradation

is the enzymatic breakdown of messenger RNA into smaller nucleotides.

Nucleases

are enzymes that hydrolyse nucleic acids by breaking phosphodiester bonds. In human cells, some mRNA molecules last only minutes, while others persist for several days before nucleases break them down.

Many eukaryotic mRNAs have a poly-A tail, which is a chain of adenine nucleotides added to the 3′ end of an mRNA after transcription. A longer poly-A tail generally helps stabilise the mRNA. As the tail gets shorter, the mRNA is less likely to be translated and more likely to be degraded.

That gives the cell precise control over timing. If a protein is needed only briefly, the mRNA coding for it can be short-lived. If a protein is needed continuously, its mRNA can be kept stable for longer. Translation can therefore be regulated without changing the DNA sequence and without necessarily changing the rate of transcription.

Epigenesis

is the developmental process in which a multicellular organism gradually forms specialised structures and functions from cells that were unspecialised at the start. The organism does not begin as a tiny pre-formed adult. Instead, patterns appear as development goes on.

Differentiation

is the process by which a cell becomes specialised by changing which genes it expresses. A neuron, a muscle fibre and an intestinal epithelial cell may all contain the same DNA sequence, but they use different sets of genes.

Epigenesis relies on stable patterns of gene activation and gene silencing. Chemical marks on DNA, or on proteins associated with DNA, produce these patterns. Epigenetic changes do not alter the DNA base sequence. The genotype stays the same, but the phenotype changes because different genes are expressed.

Be precise here: if a cytosine is chemically tagged, it is still inherited in the DNA sequence as cytosine. Epigenetic change affects access to information; it does not rewrite the information itself.

The three “-omes” are easy to mix up, so keep them clearly separated.

Genome is the complete set of genetic information in a cell, including coding and non-coding DNA sequences. In most body cells of one individual, the genome is essentially the same.

Transcriptome is the complete set of RNA transcripts made by a cell at a particular time. For this topic, mRNA matters most because it is translated into polypeptides. No cell expresses all of its genes, so the transcriptome is selective and can change.

Proteome is the complete set of proteins present in a cell at a particular time. It depends on the transcriptome, but it isn’t simply a copy of it. Some mRNAs are translated many times, some only rarely, and proteins vary in how quickly they are modified or broken down.

Comparison of genome, transcriptome and proteome in individual cells.

The pattern of gene expression drives cell differentiation. A pancreatic $\beta$ cell and a skin cell have very similar genomes, but their transcriptomes and proteomes are different. Those differences in active products give the cells their different structures and functions.

An epigenetic tag is a chemical modification attached to DNA or to a DNA-associated protein. It changes gene expression without changing the nucleotide sequence. The two syllabus examples are methylation of DNA promoters and methylation of histones.

Methylation means adding a methyl group, $-CH_3$, to a molecule. In DNA, it commonly affects cytosine bases. A methylated cytosine can still pair in DNA in the usual way, so the base sequence hasn’t changed.

When cytosine in the DNA of a promoter is methylated, transcription of the downstream gene is usually repressed. At this level, the reason is straightforward: the promoter becomes less effective at supporting transcription. Less transcription gives less mRNA, less translation and less gene product.

A nucleosome is a unit of chromatin where DNA wraps around a core of histone proteins. Histones are basic proteins that package eukaryotic DNA and help control access to it. Their tails can be chemically modified.

Methylation of amino acids in histone tails can either repress or activate transcription. You don’t need to learn the detailed molecular route for each histone mark. The key principle is this: histone methylation can change how accessible a gene is to transcription factors and transcription machinery.

This gives another example of biological inhibition: methylation at a promoter can inhibit transcription. It isn’t an inhibitor molecule competing at an enzyme active site; it’s inhibition by changing access to a gene.

Epigenetic inheritance is the transmission of a pattern of gene expression to daughter cells or offspring without a change in the nucleotide sequence of DNA. The inherited item is not a new allele; it is a continuing pattern of tags and gene activity.

During mitosis, cells can copy or maintain epigenetic tags, so daughter cells retain the parent cell’s pattern of gene expression. That’s how a specialised tissue grows and repairs itself without changing tissue type. When a liver cell divides, it should produce cells that still act as liver cells, not random unspecialised cells.

Epigenetic tags may also pass through meiosis into gametes and then into offspring. This kind of inheritance is more limited and less permanent than DNA mutation. A mutation changes the base sequence; an epigenetic tag can often be removed or reset.

Epigenome is the complete set of epigenetic tags in a cell or organism. Because the environment can influence the epigenome, epigenetic inheritance raises an interesting idea: an environmental effect on one generation may sometimes influence gene expression in the next. Be cautious here. This does not mean organisms deliberately rewrite their genes to suit the environment.

The environment can change gene expression in a single cell, or across a whole organism. Some effects happen quickly, for example when a cell responds to a signal. Others last longer and involve epigenetic tags.

Air pollution is a required example. Air pollution is contamination of air by harmful substances such as fine particulates, nitrogen oxides, ozone or organic pollutants. Exposure to polluted air has been linked with changes in DNA methylation patterns. In particular, methyl tags on DNA can be altered, which changes the expression of genes involved in inflammation, immune regulation and other cell responses.

These changes show why air pollution is more than direct tissue damage. It can change which proteins cells produce. During pregnancy, this matters especially because gene expression patterns help guide development.

Phenotypic plasticity is the ability of one genotype to produce different phenotypes in different environments. This connects well to the wider question of how the environment stimulates diversification: environmental conditions can bring out different developmental pathways or expression patterns. This does not produce new alleles, but it can create differences among individuals that selection may act on if there is heritable variation behind the response.

During the formation of eggs and sperm, most epigenetic tags are stripped away. The zygote needs that reset so it can begin a new developmental programme, rather than carry on the gene-expression pattern from a parent’s specialised cells.

Some tags remain, though. Genomic imprinting is a form of non-Mendelian inheritance where allele expression depends on whether the allele came from the mother or the father, because one parental copy is epigenetically silenced. The DNA sequence itself may be completely ordinary; what changes is which copy is allowed to be expressed.

If the active copy of a gene is faulty, imprinting can make a recessive effect show up even when another allele is present. That’s why simple dominant-and-recessive Mendelian patterns don’t explain imprinting very well.

The lion–tiger hybrids are the useful syllabus example. A liger is a hybrid offspring produced from a male lion and a female tiger. A tigon is a hybrid offspring produced from a male tiger and a female lion. Imprinting can be used to outline their phenotypic differences: paternally inherited tags may favour greater growth, while maternally inherited tags may limit growth. Because lions and tigers have different natural patterns of reproductive competition and imprinting, the direction of the cross changes the balance of growth-related gene expression.

The main consequence is clear enough: removing most tags gives the embryo a fresh start, while the small number of tags that remain can still affect phenotype in the next generation.

Monozygotic twins develop when one early embryo splits and forms two individuals with essentially the same genome. Dizygotic twins develop from two different eggs fertilised by two different sperm, so they share about the same proportion of genetic variation as ordinary siblings.

Researchers use monozygotic twin studies to investigate environmental effects on gene expression because the genetic background is held as similar as naturally possible. When genetically identical twins become less similar in a trait as they age, or after living in different environments, that points to environmental effects on gene expression or epigenetic patterns.

A good twin study doesn’t prove “environment only” or “genes only”. It helps separate their contributions. If monozygotic twins are much more similar than dizygotic twins for a condition, genetic factors are likely to be important. If monozygotic twins differ despite having essentially the same DNA sequence, then environmental effects, chance events in development and epigenetic differences become important explanations.

For D2.2, keep the focus tight: twin studies provide evidence that environment can affect gene expression, including through changes in methylation patterns over time.

External factors can change which genes are expressed. The syllabus wants one hormone example and one biochemical example in bacteria, so don’t turn this into every signalling pathway you’ve ever seen.

Hormone example: oestrogen

A hormone is a chemical messenger released by cells in one part of an organism that changes the activity of target cells elsewhere. Oestrogen is a steroid hormone, which means it can pass through the phospholipid bilayer of target cells. In cells of the uterine lining, oestrogen binds to an intracellular receptor. The hormone–receptor complex can then bind near target genes and increase their transcription.

One effect is increased expression of the gene coding for the progesterone receptor. Later in the uterine cycle, that makes the uterine lining more responsive to progesterone. The pattern is worth spotting: an external signal changes transcription factor activity, which changes gene expression, which changes cell behaviour.

Biochemical example in bacteria: lactose

A biochemical is a chemical substance produced by or used in living organisms. Lactose can act as an external biochemical signal for some bacteria. In Escherichia coli, the genes needed for lactose uptake and breakdown are expressed when lactose is available and repressed when lactose is absent.

An operon is a cluster of bacterial genes controlled together by a shared regulatory region. In the lac operon, a repressor protein blocks transcription when lactose is absent. When lactose is present, it binds in a way that inactivates the repressor, allowing RNA polymerase to transcribe the genes for lactose use.

This gives a clear example of inhibition in a biological system. The repressor inhibits transcription; lactose removes that inhibition. It also shows how the environment can stimulate diversification of cell activity: bacteria with the same genome can switch to a different expression pattern when the available nutrient changes.