Overview of operons, regulatory DNA sequences, & regulatory genes. Repressor & activator proteins.
- Bacterial genes are often found in operons. Genes in an operon are transcribed as a group and have a single promoter.
- Each operon contains regulatory DNA sequences, which act as binding sites for regulatory proteins that promote or inhibit transcription.
- Regulatory proteins often bind to small molecules, which can make the protein active or inactive by changing its ability to bind DNA.
- Some operons are inducible, meaning that they can be turned on by the presence of a particular small molecule. Others are repressible, meaning that they are on by default but can be turned off by a small molecule.
We tend to think of bacteria as simple. But even the simplest bacterium has a complex task when it comes to gene regulation! The bacteria in your gut or between your teeth have genomes that contain thousands of different genes. Most of these genes encode proteins, each with its own role in a process such as fuel metabolism, maintenance of cell structure, and defense against viruses.
Some of these proteins are needed routinely, while others are needed only under certain circumstances. Thus, cells don't express all the genes in their genome all the time. You can think of the genome as being like a cookbook with many different recipes in it. The cell will only use the recipes (express the genes) that fit its current needs.
How is gene expression regulated?
There are various forms of gene regulation, that is, mechanisms for controlling which genes get expressed and at what levels. However, a lot of gene regulation occurs at the level of transcription.
Bacteria have specific regulatory molecules that control whether a particular gene will be transcribed into mRNA. Often, these molecules act by binding to DNA near the gene and helping or blocking the transcription enzyme, RNA polymerase. Let's take a closer look at how genes are regulated in bacteria.
In bacteria, genes are often found in operons
In bacteria, related genes are often found in a cluster on the chromosome, where they are transcribed from one promoter (RNA polymerase binding site) as a single unit. Such a cluster of genes under control of a single promoter is known as an operon. Operons are common in bacteria, but they are rare in eukaryotes such as humans.
Diagram illustrating what an operon is. At the top of the diagram, we see a bacterial cell with a circular bacterial chromosome inside it. We zoom in on a small segment of the chromosome and see that it is an operon. The DNA of the operon contains three genes, Gene 1, Gene 2, and Gene 3, which are found in a row in the DNA. They are under control of a single promoter (site where RNA polymerase binds) and they are transcribed together to make a single mRNA that has contains sequences coding for all three genes. When the mRNA is translated, the three different coding sequences of the mRNA are read separately, making three different proteins (Protein 1, Protein 2, and Protein 3).
Note: The operon does not consist of just the three genes. Instead, it also includes the promoter and other regulatory sequences that regulate expression of the genes.
In general, an operon will contain genes that function in the same process. For instance, a well-studied operon called the lac operon contains genes that encode proteins involved in uptake and metabolism of a particular sugar, lactose. Operons allow the cell to efficiently express sets of genes whose products are needed at the same time.
Anatomy of an operon
Operons aren't just made up of the coding sequences of genes. Instead, they also contain regulatory DNA sequences that control transcription of the operon. Typically, these sequences are binding sites for regulatory proteins, which control how much the operon is transcribed. The promoter, or site where RNA polymerase binds, is one example of a regulatory DNA sequence.
Diagram illustrating that the promoter is the site where RNA polymerase binds. The promoter is found in the DNA of the operon, upstream of (before) the genes. When the RNA polymerase binds to the promoter, it transcribes the operon and makes some mRNAs.
Most operons have other regulatory DNA sequences in addition to the promoter. These sequences are binding sites for regulatory proteins that turn expression of the operon "up" or "down."
- Some regulatory proteins are repressors that bind to pieces of DNA called operators. When bound to its operator, a repressor reduces transcription (e.g., by blocking RNA polymerase from moving forward on the DNA).
Diagram illustrating how a repressor works. A repressor protein binds to a site called on the operator. In this case (and many other cases), the operator is a region of DNA that overlaps with or lies just downstream of the RNA polymerase binding site (promoter). That is, it is in between the promoter and the genes of the operon. When the repressor binds to the operator, it prevents RNA polymerase from binding to the promoter and/or transcribing the operon. When the repressor is bound to the operator, no transcription occurs and no mRNA is made.
- Some regulatory proteins are activators. When an activator is bound to its DNA binding site, it increases transcription of the operon (e.g., by helping RNA polymerase bind to the promoter).
Diagram illustrating how an activator works. The activator protein binds to a specific sequence of DNA, in this case immediately upstream of (before) the promoter where RNA polymerase binds. When the activator binds, it helps the polymerase attach to the promoter (makes promoter binding more energetically favorable). This causes the RNA polymerase to bind firmly to the promoter and transcribe the genes of the operon much more frequently, leading to the production of many molecules of mRNA.
Where do the regulatory proteins come from? Like any other protein produced in an organism, they are encoded by genes in the bacterium's genome. The genes that encode regulatory proteins are sometimes called regulatory genes.
Many regulatory proteins can themselves be turned "on" or "off" by specific small molecules. The small molecule binds to the protein, changing its shape and altering its ability to bind DNA. For instance, an activator may only become active (able to bind DNA) when it's attached to a certain small molecule.
Diagram illustrating how a hypothetical activator's activity could be modulated by a small molecule. When the small molecule is absent, the activator is "off" - it takes on a shape that makes it unable to bind DNA. When the small molecule that activates the activator is added, it binds to the activator and changes its shape. This shape change makes the activator able to bind its target DNA sequence and activate transcription.
Operons may be inducible or repressible
Some operons are usually "off," but can be turned "on" by a small molecule. The molecule is called an inducer, and the operon is said to be inducible.
- For example, the lac operon is an inducible operon that encodes enzymes for metabolism of the sugar lactose. It turns on only when the sugar lactose is present (and other, preferred sugars are absent). The inducer in this case is allolactose, a modified form of lactose.
Other operons are usually "on," but can be turned "off" by a small molecule. The molecule is called a corepressor, and the operon is said to be repressible.
- For example, the trp operon is a repressible operon that encodes enzymes for synthesis of the amino acid tryptophan. This operon is expressed by default, but can be repressed when high levels of the amino acid tryptophan are present. The corepressor in this case is tryptophan.
These examples illustrate an important point: that gene regulation allows bacteria to respond to changes in their environment by altering gene expression (and thus, changing the set of proteins present in the cell).
Some genes and operons are expressed all the time
Many genes play specialized roles and are expressed only under certain conditions, as described above. However, there are also genes whose products are constantly needed by the cell to maintain essential functions. These housekeeping genes are constantly expressed under normal growth conditions ("constitutively active"). Housekeeping genes have promoters and other regulatory DNA sequences that ensure constant expression.
Want to join the conversation?
- what is the evolutionary advantage of regulation of prokaryotic gene expression?
what are the drawbacks?(17 votes)
- Great question. The upsides of gene regulation is a conservation of energy within the body, as it is not being used for unnecessary functions. The drawbacks could maybe be the possible mutations? If there was a mutation that were to transcribe a protein non-stop, it could satiate the cells or use up available resources for no reason.(19 votes)
- What does it mean for there to be a negative and positive gene regulation? What's the difference?(7 votes)
- Positive gene regulation controls the production of genes by turning them on while negative gene regulation controls the production of genes by turning them off. Positive gene regulation allows for the production of a gene that is needed for use at a particular time/situation in a cell while negative gene regulation prevents the overproduction of a gene at a particular time/situation in a cell.(10 votes)
- Can you give a couple examples of rare eukaryotic operons?(4 votes)
- The examples that I found for mammals are all bicistronic (operons with two genes):
LASS1-GDF1, SNRPN-SNURF, MTPN-LUZP6 and MFRP-C1QTNF5
You can search for those gene pairs, but there doesn't seem to be a huge amount of information available and in many cases one of the genes is almost completely uncharacterized.
Eukaryotic operons (aka polycistronic mRNAs) are apparently very common in nematodes (round worms) and also frequently seen in Drosophila (a fly).
Unfortunately I have only found academic papers that cover this interesting phenomenon:
Does that help?
Also, the mitochondrial genome uses operons (polycistronic genes), but since the mitochondria is descended from a bacteria it seems like cheating to count that ...(9 votes)
- How can the cell know that the genes in an operon are separate? Wouldn't the cell create all the genes in a operon as one gene and make them all as a whole protein?(2 votes)
- Good question!
Even though all the genes in an operon are transcribed together, they are not translated together. There are untranslated sequences between each gene that contain a RBS (ribosome binding site). When the mRNA is being translated, the RBSs for each gene will independently bind to different ribosomes and so they all make separate proteins.
This figure may help make things clearer:
- Are the operator and enhancer exist at the same time?(2 votes)
- Yes. there could be enhancer or silencer.
The operator is a place of operon where repressor binds while enhancer is a place where activator binds. They could easily be neighboring coding sequences on the same operon.(2 votes)
- What would happen if a eukaryotic cell attempted to use an operon structure for its genes? What is the difference in translation between eukaryotes and prokaryotes that would cause this to happen?(2 votes)
- Even though Operons exist only in Prokaryotes there are few Eukaryotes such as Nematode C, elegans.
Also, polycistronic RNA is present only in Prokaryotes.
So you ask for that 'switch' during translation to result in the formation of the operon in Eukaryotes?
Also, operons exist in the range of rRNA, so not mRNA but rRNA.
There is no specific step which would imply there is a difference. There are just clusters of genes and then single regulated genes.
Numerous instances of polycistronic transcription in eukaryotes, from protists to chordates, have been reported. These can be divided into two broad types. Dicistronic transcription units specify a messenger RNA (mRNA) encoding two separate genes that are transported to the
cytoplasm and translated in that form.
Eukaryotic operons often result in coexpression of functionally related proteins.
That has to do with trans and cis slicing:
Once trans-splicing exists, it is very difficult or impossible for an organism to lose it — it is essentially a one-way street. This is because of the region of the RNA between the promoter and the trans-splice site is
spliced out before the RNA is translated, so it can and does accumulate out-of frame AUGs.
- Is operator a kind of silencer?(1 vote)
- Not operator itself, it is just place where repressor binds. But when repressor binds it is silencer.(2 votes)
- What is gene interaction?(1 vote)
- When two genes are expressed.
When one gene controls the expression of another gene.(1 vote)
- Is being constitutively active exclusively a feature of prokaryotes, or do eukaryotes express this as well (perhaps to a lesser extent)?
Thank you.(1 vote)