Bacteria are small, but they are not genetically simple. A single bacterial cell constantly adjusts which genes it uses in response to nutrients, temperature, stress, chemicals, and signals from other cells. It does not need every gene to be active at all times. Instead, it turns genes on when their products are useful and turns them down or off when they are not.
This ability is called gene regulation. In bacteria, much of that regulation happens at the stage of transcription, when information in DNA is copied into RNA. The central question is therefore not simply whether a gene is present, but whether the cell allows its DNA to be read.
What does it mean to turn a bacterial gene on?
A gene is considered “on” when the cell is actively using its information to make a functional product, usually a protein or a functional RNA molecule.
For protein-coding genes, the process begins when RNA polymerase, an enzyme that makes RNA, binds to a region of DNA called a promoter near the gene. If transcription proceeds, RNA polymerase copies the gene into messenger RNA (mRNA). The mRNA can then be used by ribosomes to make a protein.
Turning a gene off generally means preventing or reducing transcription. Turning it on means allowing or increasing transcription.
Gene regulation is rarely a simple light switch. A bacterial cell can produce a great deal of a particular protein, a small amount, or almost none, depending on what the cell needs.
How RNA polymerase starts transcription
RNA polymerase does not normally begin copying DNA at random. It recognizes particular DNA sequences associated with promoters.
In many bacteria, a protein component called a sigma factor helps RNA polymerase recognize the appropriate promoter. Different sigma factors can redirect RNA polymerase toward different sets of genes. For example, a bacterium can use one sigma factor for routine growth and another to activate genes needed during a particular environmental stress.
Once RNA polymerase is positioned at a promoter, it can begin synthesizing an RNA strand using one DNA strand as a template.
This gives bacteria an efficient point of control: if transcription does not begin, the cell generally does not need to spend resources making the corresponding mRNA and protein.
Repressors can keep genes off
One of the most important bacterial gene-regulation mechanisms involves repressor proteins.
A repressor is a regulatory protein that binds to a specific DNA sequence, often called an operator, and interferes with transcription. Depending on the regulatory system, it may physically obstruct RNA polymerase or prevent transcription from proceeding efficiently.
A classic example is the lac operon in Escherichia coli. The genes in this system help the bacterium use lactose as an energy source. When lactose is unavailable, a repressor helps keep the relevant genes largely inactive.
When lactose is present, a lactose-derived molecule interacts with the regulatory system and reduces the repressor’s ability to block transcription. The genes can then be expressed, allowing the cell to make proteins involved in lactose utilization.
This arrangement prevents the bacterium from continuously producing proteins it does not need.
Activators can help turn genes on
Bacteria can also increase transcription with activator proteins.
An activator binds to a regulatory DNA sequence and helps RNA polymerase bind to or function at a promoter. The result is increased transcription.
The lac system illustrates another important principle. The presence of lactose alone does not necessarily produce the highest possible level of lac gene expression. The cell also responds to the availability of glucose, a preferred carbon source.
When glucose is scarce, E. coli increases levels of a signaling molecule called cyclic AMP (cAMP). cAMP binds to the CAP protein, also known as the catabolite activator protein. The resulting complex can bind near the lac promoter and promote transcription.
The bacterium is therefore integrating more than one piece of information: Is lactose available, and is glucose scarce? This lets the cell adjust gene expression according to its metabolic situation rather than responding to a single signal in isolation.
Many bacterial genes are controlled together
Bacteria often organize related genes into groups called operons.
An operon typically contains several genes controlled by a common promoter and regulatory region. When the promoter is activated, RNA polymerase can transcribe the genes together into a single RNA molecule containing information for multiple proteins.
This arrangement is particularly useful when the proteins perform related jobs. A cell that needs an entire metabolic pathway can activate several of its components at once rather than regulating every gene independently.
Two classic examples are the lac operon, which responds to lactose availability, and the trp operon, which helps E. coli produce the amino acid tryptophan.
The trp operon demonstrates the opposite regulatory logic from the lac system. When tryptophan is scarce, the genes needed to make it are expressed. When tryptophan is abundant, the cell reduces their expression. In this way, the pathway is closely tied to the amount of its end product.
Bacteria can regulate genes after transcription begins
Control does not stop with the decision to start transcription.
Some bacterial regulatory systems influence how transcription proceeds after RNA polymerase has already begun. In attenuation, for example, features of a newly forming RNA molecule can influence whether transcription continues into downstream genes.
Bacteria also regulate gene expression at the level of translation, the process in which ribosomes read mRNA to make proteins. Regulatory RNAs and RNA-binding proteins can affect whether a ribosome can access an mRNA or how stable that mRNA is.
This creates several opportunities for control:
- whether transcription starts
- whether transcription continues
- how long an mRNA survives
- whether ribosomes translate the mRNA
- how much functional protein remains active in the cell
Using multiple levels of control allows bacteria to respond quickly while conserving resources.
Small RNAs add another layer of control
Bacterial cells produce many short RNA molecules known as small regulatory RNAs or sRNAs.
Some sRNAs bind to specific mRNAs and change their stability or their accessibility to ribosomes. Depending on the system, an sRNA can increase or decrease production of a particular protein.
Because RNA can be produced and altered relatively quickly, RNA-based regulation can provide a rapid response to changing conditions such as nutrient limitation or environmental stress.
Some bacteria also use riboswitches, regulatory segments of RNA that can directly sense small molecules. When a molecule binds to a riboswitch, the RNA can change shape and alter transcription or translation of the associated gene.
Environmental signals can change entire gene programs
Bacteria constantly encounter changing conditions. A nutrient may disappear, the temperature may shift, oxygen may become limited, or a harmful chemical may appear.
Rather than responding to each change with a single gene, bacteria often coordinate groups of genes through regulatory networks.
A regulatory protein may sense a particular chemical or physical condition and then alter transcription of numerous genes. A sigma factor may redirect RNA polymerase to a different collection of promoters. Other signaling systems can transmit information from the cell surface or surroundings to DNA-binding regulators inside the cell.
This allows a bacterium to change its physiological state. It might alter metabolism, activate stress defenses, modify its cell surface, or adjust its ability to move.
Gene regulation can depend on more than the environment
Bacteria can also regulate genes according to signals produced by other bacteria.
In quorum sensing, bacteria release and detect signaling molecules whose concentration can reflect the density or activity of nearby cells. Once a signal reaches an appropriate level, it can trigger changes in gene expression.
Different bacterial species use different quorum-sensing systems, and the regulated behaviors vary. They can include coordinated production of extracellular substances, changes in movement, or other group behaviors.
The important point is that bacterial gene regulation is not limited to a cell responding independently to its physical surroundings. Some bacteria can alter gene expression in response to chemical information about neighboring cells.
Why turning genes off matters as much as turning them on
Gene regulation is not simply a way for bacteria to activate useful traits. Shutting down unnecessary genes saves energy and materials.
Making RNA and proteins requires cellular resources. If a nutrient-processing enzyme is useless because its nutrient is absent, producing large quantities of that enzyme is wasteful. Regulation lets the cell redirect its resources toward functions that are more valuable under current conditions.
Regulation also improves timing. A bacterium may need a protein only briefly, such as during a stress response. Once the threat passes, reducing production prevents the cell from maintaining an expensive response indefinitely.
Gene regulation helps bacteria adapt without changing their DNA
A crucial distinction is that changing gene expression is not the same thing as changing the underlying DNA sequence.
If a bacterium encounters a new condition and activates a stress-response gene, the gene itself has not necessarily mutated. The cell has simply changed how strongly it uses existing genetic information.
This can produce substantial changes in the cell’s behavior without requiring a new mutation. Mutations can also alter regulatory regions or regulatory proteins, and natural selection can favor such changes when they provide an advantage. But everyday regulation is generally a reversible adjustment in gene activity.
Gene regulation and antibiotic resistance
Gene regulation also matters in clinically important bacterial behavior.
Some bacteria can regulate genes involved in drug resistance, transport systems, stress responses, and changes to the cell envelope. A resistance trait may therefore depend not only on whether resistance-related genes exist, but also on when and how strongly they are expressed.
In some cases, exposure to an environmental condition can alter regulatory pathways and change the production of proteins that help the bacterium survive that condition. Other resistance mechanisms result from genetic changes that permanently alter the DNA.
Understanding bacterial gene regulation is consequently important for understanding how bacteria respond to antibiotics and other pressures.
The basic logic is simple, even when the networks are complex
At its core, bacterial gene regulation follows a practical principle: use genetic information when its products are useful, and limit production when they are not.
Promoters determine where transcription can begin. RNA polymerase carries out transcription. Repressors can inhibit transcription, while activators can promote it. Operons allow related genes to be regulated together. Sigma factors can redirect transcription toward different groups of genes, while regulatory RNAs and other mechanisms provide additional control after transcription begins.
The result is a cell that can continually adjust its genetic activity to match its circumstances. Bacteria may have only a single cell and relatively compact genomes, but their gene-regulatory systems give them remarkable control over what that cell does, when it does it, and how strongly it responds.
