• Question: How does certain genetic information get switched on or off?

    Asked by abiiii on 1 May 2020.
    • Photo: Kim Liu

      Kim Liu answered on 1 May 2020: last edited 1 May 2020 1:43 pm

      Great question πŸ™‚ ‘Regulation of gene expression’ is a massive subsection of molecular and cellular biology, and I think your previous questions have nicely shown why it is so important. Cells have a multitude of ways of doing this, and happens at all stages of a gene’s production.

      The production of a gene involves three important steps – first DNA, our blueprint, is converted into an intermediate messenger known as RNA. This message is then translated into a protein by the ribosome, which stitches biological building blocks together into proteins. Each of these steps has a variety of checkpoints which can cause a gene to be turned on or off.

      I’ll stick to one I find particularly interesting – modified DNA bases. You may know that the genetic alphabet is made up of 4 letters G, C, T and A. Sequences of these letters give the instructions of how to make proteins. Chemical modifications on these letters act like accents in a language – they give extra information about how the code should be read. For example one common modification called C methylation (let’s pretend it’s Δ†) leads to genes being turned off. Cells can sometimes do this if they detect the gene has become damaged in some way. Other less well known accents of C have currently unknown functions, and there may be modifications/accents on the other letters as well.

      There are so many interesting answers to this question – I’m sure there will be other cool mechanisms of gene regulation described here as well πŸ™‚

    • Photo: Melanie Krause

      Melanie Krause answered on 1 May 2020:

      Great answer from Kim already! There is more ways to switch genes on or off though.
      One of them is by how tightly the DNA is ‘curled’. In the nucleus where the genetic information of a cell sits there are also proteins called ‘Histones’. These play a role in curling up the DNA in a way that makes it fit into a tiny cell. If DNA was completely unwrapped it could be up to 2 meters long so rolling it up tightly is important to make it fit.
      However.. if the DNA is packaged too tightly.. the enzymes that want to read the information to make copies in order to produce proteins can’t access it. This process is modulated by Histones. So if you want to switch off a gene you could also make the histones curl up the DNA more highly and then loosen it if you need the gene to be on πŸ™‚

    • Photo: Kyren Lazarus

      Kyren Lazarus answered on 1 May 2020:

      This is a great question. Kim as answered it superbly and he is talking about a field called epigenetics where scientists study how gene expression is modified. One example is methylation which Kim has described below.

      Another way that genetic information can be regulated is by transcription factors. These are proteins that bind to DNA, specifically just upstream of the start site. This area is called the promoter region and is usually the area where an enzyme called RNA polymerase binds to, which then allows the conversion of DNA to RNA in the process of transcription.

      One way that the transcription factor can turn on a gene is by enhancing or enabling the process of transcription.

    • Photo: Freya Harrison

      Freya Harrison answered on 1 May 2020:

      I can see how this is related to your other question! Cells can switch genes on or off more or less permanently, for example by methylating bits of DNA as Kim has explained. This is useful when cells develop into a particular specialised type, they can methylate genes that they won’t ever need to do their job.

      But there are also lots of genes which cells might need to switch on sometime, but off at other time. To do this, they use a more flexible switching system based on proteins which reversibly bind to DNA.

      At the start of each gene is a region called a promoter. Specialised proteins called transcription factors can bind to the promoter, and then RNA polymerase binds to the transcription factor to start transcribing the gene into RNA to switch the gene on. Other proteins in the cell can act as transcriptional activators – they make it easier for transcription factors to bind the promoter or to recruit RNA polymerase. And other proteins are transcriptional repressors. They can bind to a gene’s promoter and stop the transcriptions factors or the RNA polymerase getting into place and starting transcription.

      To “decide” whether to switch a gene on or off, the cell senses information – like is it low on a particular molecule it needs, has it got too much of something. And then it switches the right genes on and off to make more of the molecule it needs, or get rid of the excess molecule it has too much of. The molecules that sense these signals are enzymes that slightly alter the structure of transcription factors, activators or repressors. Altering the structure makes these proteins active or inactive, so they can be switched on or off, and that determines if the gene is switched on or off.

      So: there are a few layers of control here. A signal changes the activity of an enzyme, which switches proteins that control transcription on or off, which switches transcription on or off. But this system can be very quick and finely tuned, so that a cell switches on the genes it needs at any particular time.

    • Photo: Ailith Ewing

      Ailith Ewing answered on 1 May 2020:

      This is such a great question! And as you can see from the answers there are loads of ways that genes are turned on or off.

      Another way that genes can be turned on or off, is through mutations to the DNA. In addition to the modifications that Kim described, sections of DNA sequence for a gene can sometimes be missing from the blueprint. When this happens it can sometimes mean that that section of the blueprint is not converted to RNA and is not translated into protein.

      It can also be the case that there are extra copies of a section of DNA which can mean that the gene is more active that it should be.

      These changes happen a lot in the DNA of cancer cells where the systems that control the cell are not working properly.

    • Photo: Max Furst

      Max Furst answered on 1 May 2020:

      Kim is right – there are loads of ways to answer this question.
      I’m going to be super pedantic here (sorry!!) and point out that your question is a bit off imo. I would say that genetic information isn’t switched on and off, it either exists or it doesn’t. I’m saying this because to me it’s not 100% clear what your question refers to; it could be that you mean what Kim has been giving you an example for, “How does a certain gene get switched on or off”. It could also be that you mean “How is certain genetic information introduced or removed?” As you already have an example for the first question, and because there is so many (epigenetics, inducible promoters, transcription factors, RNAi, …), I’ll answer the second interpretation.

      In eukaryotic organism (like animals), the genetic material doesn’t really vary much, all cells contain the same DNA (=the genetic information), unless a spontaneous mutation arises during mitosis, but that would mean just a small change. A more likely event where bigger chunks of genetic information gets gained or lost is during meiosis. Think of blood type for example: if a person with blood type O has a child with someone with blood type A, then you could say the genetic information for producing the antigen A has been gained, because one parent gave that child the allele of the gene that encodes the enzyme that modifies the antigens on blood cells to type A. If the child had had two parents with blood type O, it would have not gotten that information.
      Probably, this is not where your question was going though.

      Maybe if we look into other organisms, such as bacteria, something happens that comes closer: horizontal gene transfer. That means, that bacteria tend to sometimes simply pick up DNA that they find in their environement. That can be observed quite easily with genes that confer a massive evolutionary advantage, e.g. antibacterial resistance. Though probably a rare event, it can happen say, that a person catches a harmless bacterium that happens to be resistent to penicilin, but doesn’t cause any disease. The next day, the same person catches another bug that causes pneumonia. Now you go to the hospital and they try and treat your disease with penicilin, but it doesn’t work. Why? Because it so happened that some cells of the nasty bug got in contact with the harmless bacterium resistent to penicilin and they took up the gene that conferred that resistance. This can happen in several ways, one is that bacteria store the gene on an extra chromosome that is available in many copies and is very small (a plasmid). This plasmid can easily leave the cell and other bacteria can snatch it up, then it works inside them as well. That is a true case of extra genetic information being gained.

      Last example is “non-natural”: we can add and remove genetic information in the lab. Nowadays, scientists have a range of tools to do that. You may have heard of the scientist in China that used the new Crispr/Cas system to manipulate the genome of babies. This scientist edited a gene in the embryo called CCR5, which he changed such that it becomes inactive, because that may cause the resulting humans become immune to HIV. Now that is a very controversial case, because editing humans has massive ethical issues. What happens really routinely in labs (such as mine), however, is that we change the genome of more primitive organisms, especially of bacteria. We do that, so we can convince the bacteria to make something useful for us. For example, this technology allows us to produce large amounts of human insulin, a protein used to treat diabetes. This is done by copying the gene that encodes for the insulin protein from a human genome, put it in a plasmid (as mentioned before) and give that to a bacterium. Now that bacterium will produce insulin, just as a healthy human would. We can grow massive amount of the bacterium, isolate insulin, and give that to diabetes patients. That was another way of how genetic information can be gained – by adding it artificially in the lab.

    • Photo: Bilal Ahsan

      Bilal Ahsan answered on 2 May 2020:

      Great question and awesome answers already!
      Here are my two cents; genetic information stored in genes can be switched on or off by cellular machinery; mostly a plethora of proteins that can bind to DNA and make it inaccessible and thereby incapable of expressing its information. Then the question would be, how a plethora of proteins know when and which part of the gene they need to bind to switch that on or off? The simplest answer is that there are tiny molecules – much smaller than the proteins – such as methyl groups, that can bind with the proteins and guide them where to bind. Certain proteins, such as histones, are already bound to DNA and they simply make the DNA-bound protein complex more compact. This process called ‘epigenetic regulation’ is already explained in detail another answers.

    • Photo: Nina Rzechorzek

      Nina Rzechorzek answered on 2 May 2020:

      Hi abiiii
      Just to add that the levels of gene activity within a cell can also vary by time of day – part of the cellular clockwork! Also – did you know that viruses ‘trapped’ in our genome may affect the activity of our genes which can determine how our brain develops and functions?
      This makes it much more complicated (but also very exciting!) πŸ™‚

    • Photo: Anna Dickson

      Anna Dickson answered on 2 May 2020:

      Great question and great answers so far – there are so many different ways that this occurs!

      As mentioned Max, we sometimes use technologies to edit the genetic information of cells. In my lab we do this in mammalian cells in cell culture – which is no where near as ethically controversial as doing this in human embryos. In the lab, we try to turn some genetic material off in cells so that we can study the role of that gene. For example, if we know that a certain disease is caused by a specific gene (e.g. deletion of BRACA1 is well known to increase the likelihood of cancer), we can use the CRISPR/Cas9 technology to turn off that specific gene. This is very useful as as we can compare the function of the cells with or without the gene we are interested in to help us understand how it works and how the gene contributes to the disease.

    • Photo: Eleanor Raffan

      Eleanor Raffan answered on 4 May 2020:

      It looks like you already have some great answers to this question. But has anyone mentioned how female animals cope with having two copies of the X (sex) chromosome? Male animals only have one copy of the X chomosome (which is paired with a male Y). Bodies wouldn’t work if females had a double dose of all the genes that are present on their X chromosomes. So every cell in the body of a female randomly inactivates one of the two X copies. Mostly it doesn’t make much difference which one is inactivated but if an X chromosome gene has a different version on the two chromosomes, it can lead to visible effects. The best example I know is the tortoishell pattern in female cats. You can read about that here: https://www.nature.com/scitable/topicpage/x-chromosome-x-inactivation-323/