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What will happen if we relocate genes?

  1. Jun 26, 2015 #1
    We have got in human genome about 21 000 genes and they are distributed among 46 chromosomes more or less equally.

    Now imagine that we can relocate all these genes (I mean the genes that produce mRNAs that encodes proteins) in one/two/three/several chromosomes and all the rest chromosomes contain just non-coding RNAs (more precisely the genes producing non-coding RNAs), would this matter? In other words, does the rule of arrangement of genes matter and work? Imagine that in some certain chromosome we have got Gene N1, Gene N 2, Gene N 3 located in neighborhood. And then we have got this order Gene N2, Gene N 3, Gene N 1. Would this change something in human genome and behavior? :oldeyes:
     
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  3. Jun 26, 2015 #2
    I am pretty sure this would end up with a non functional organism since genes are switched on and off by various factors,
    and those factors at least in some cases could rely on the gene to be switched existing at a certain location.
     
  4. Jun 27, 2015 #3
    Gene activation, use and protection is dependent on spatial location. As an example it seems the way eukaryotes hook up chromosomes against the nuclear wall is going to become another "-ome" area of massive study, because it affects all these things.

    Besides, even if you tidy up the chromosomes, they wont stay that way for very long. - But Ma Nature, I cleaned my room yesterday! - That was then - look how untidy it is. Now you have to do it all over again. - Silly room!
     
  5. Jun 27, 2015 #4

    Ygggdrasil

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    In the human genome, you would expect to see changes in genome function if you rearranged genes on the chromosome. As rootone said, human genes are subject to regulation from many sequences (called enhancers) that lie far away from the gene they regulate. Furthermore, animal genomes often contain regions that are epigenetically marked to be silent (heterochromatin) or active (euchromatin), and whether a gene lies in a heterochromatic or euchromatic region can determine whether it gets expressed or not. This phenomenon (called the position effect) is very well studied in fruit flies and has been shown to happen in other organisms as well.

    That said, some organisms, like bacteria or yeast, do not rely on many long-range interactions for gene regulation and "shuffling" the genome may be possible. Indeed, a consortium of researchers has built an artificial yeast chromosome that they can randomly shuffle the genes around in order to test some of the questions you're asking (http://www.nature.com/news/first-synthetic-yeast-chromosome-revealed-1.14941). The group has a paper where they "circularly permute" a yeast chromosome and find that certain rearrangements of the chromosome cause some unexpected phenotypes: http://www.pnas.org/content/111/48/17003.long
     
  6. Jun 28, 2015 #5
    So is the distance between protein-coding genes and regulatory genes very important? And if this distance changes then the rate of transcription will also change?

    Well, English is not my native language; could you please re-state this sentence? I want to know what chromosomes have got to do with nuclear wall and gene expression.

    If so, I will a bit change my question: imagine that we re-arrange genes WITH ENHANCERS, in other words the distance between genes and enhancers stays the same and this complex (gene+enhancer) moves to other location and so does all other complexes, would this change anything?

    Yes, I know about them, but according to Wikipedia:

    https://en.wikipedia.org/wiki/Euchromatin

    So, in most cases the genes will be active. Actually I wanted to know what would happen if the order of genes is changed, for example in one certain chromosome fully being euchromatic.

    Wow, It is a great leap since Craig Venter’s time.:rolleyes:

    Yes, I wanted to know exactly this. As I understood they simply created ONE chromosome of the Saccharomyces cerevisiae but during this process they re-arranged the order of genes, right? So, gene re-arrangement DOES change something in organism.
     
  7. Jun 28, 2015 #6

    Ygggdrasil

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    Unfortunately, we don't really understand enough about enhancers to know what causes certain enhancers to interact with certain genes. Some of it may be biochemical specificity (certain transcription factors in the enhancer interact with certain factors in the promoter of the gene) and some could do with the overall "folding" of the genome in the nucleus (which places certain sequences far from each other and other sequences close to each other). There are also sequences called insulator sequences that can interfere with enhancer-promoter interactions.

    What we do know, for example, from studies in fruit flies. Is that inserting genes at random in different parts of the cell will have very different effects on the expression of that gene. The context of the DNA sequences and chromatin structure surrounding a gene do seem to be very important in determining the regulation of the gene, though we don't have a complete understanding yet of how this works.


    Yes. You can read the paper for more details (it should be free to read): http://www.pnas.org/content/111/48/17003.long
     
  8. Jul 1, 2015 #7
  9. Jul 4, 2015 #8
    I am sorry, I can't find that reference now, so never mind.

    [In case you are curious, my impression was that gene regulation could also work by having proteins tie up parts of the chromosomes against the nuclear wall. Hence down regulating gene expression in long parts of the chromosome in the same manner as histones do more locally and in a more regular fashion.]
     
  10. Jul 4, 2015 #9

    Ygggdrasil

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    I think you're refering to lamin-associated domains. Researchers have mapped which genes tend to associate with the wall of the nucleus (one of the main proteins in the nuclear envelope is a structural protein called lamin), and found that lamin-association correlates with gene repression. It's currently not clear whether there is a causative relationship either from association with the nuclear envelope causing gene repression or gene repression causing lamin association. Here's a review from last year on the topic: http://www.sciencedirect.com/science/article/pii/S0955067414000283
     
  11. Jul 20, 2015 #10
    Excuse me, but I do not quite understand this. Do you mean that chromosomes are bound to nucleus wall? And hence they DO NOT swim in nucleoplasm?
    I never thought that genes, that is part of DNA can directly bind to nucleus wall!:bugeye:
     
  12. Jul 20, 2015 #11

    Ygggdrasil

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    The lamin-associated domains show statistically tendency to associate with the nuclear envelope than other regions of the genome. This does not necessarily mean that they are stably bound to the nuclear envelope (current evidence argues that this is not the case http://www.sciencedirect.com/science/article/pii/S0092867413002171), but if you average over many cells in a population and over many points in the cell cycle, you see these trends emerging.

    That said, chromosomes in the nucleoplasm are not freely diffusing and there seems to be a great deal of organization inside of the nucleus. For example, chromosomes tend to occupy distinct territories within the nucleus instead of DNA from different chromosomes being intermixed throughout the nucleus. Here's a good review on what we know about the organization of DNA inside the nucleus, though this is an active area of research that we are still trying to understand: www.annualreviews.org/doi/full/10.1146/annurev-genom-091212-153515
     
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