Random gene?

[Olivia Gallup :)]

Is there a DNA sequence/device that can randomly pick a gene out of a group of genes to be expressed? For instance, if there are 5 different pigmentation proteins encoded in the DNA but you only want one of them to be expressed at a time, can you make the cell pick one of the colors at random? 

[Koeng]

Yea, but it would probably be difficult. Perhaps have a bunch of repressors that all repress each other so one wins in the end and represses all the others (Kind of what lambda does). It could be easier to do this with interfering CRISPRs, but also not worth the effort to make it.

-Koeng

[Nathan McCorkle]

If they're indeed already "to be expressed" then you might be able to
repress them like these folks did for flowers:
https://en.wikipedia.org/wiki/RNA_interference#History

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[Josiah Zayner]

Your question is interesting but not quite clear could you be more specific? What do you mean by pick one of the genes at random?
If a transcription factor is always picking one of the genes at random then the cell will not produce only one pigment, which I think is what you are after?
If you want each cell to randomly activate one and only one of the genes this becomes much more difficult.

Understand that _nothing_ in biology is _random_ what this means is that choosing your gene needs to be regulated by _something_. Temperature, light, pressure, amount of a transcription factor.

Next, once a genetic change is made, say by using Lox/Cre or CRISPR, there is no going back(or it is very very complicated) so the "randomness" would only be good for one generation. i.e. you transform a bacteria with the original plasmid and it will randomly be a color but each generation after that will be the same color.

However, if that is all you want then the simplest approach would probably best be done by creating a library of plasmids with promoters that allows a constitutively active transcription factor to activate only one of the genes at a time in the cell. Then transforming your bacteria with all of them and each will contain a random gene that they activate for one generation or maybe multiples to create different combinations of pigments.

[Salva Duran]

http://en.wikipedia.org/wiki/Brainbow

Although I'm not sure all colors are expressed with the same probability.

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[Mega [Andreas Stuermer]]

What if you change the cells DNA polymerase against TAQ-pmase? Then it will make lots of errors, frequently destroying the proteins :D

[Olivia Gallup :)]

Sorry for being ambiguous; I want each cell to activate only one of the genes for the duration of its whole life cycle, and I do understand that nothing in biology is random, which is why I posted this question to ask you guys for ideas :) To choose the gene to be activated also has to be completely up to the cell without any outside genetic manipulation, so no CRISPR or Lox/Cre. In every "newborn" cell, the process for choosing the gene that the cell will express for its whole life has to restart, so that a daughter cell does not look exactly like its parent cell. 

The brainbow technique for marking cells like this from @Salva would be a great solution actually, except that it would only work for one generation, and in each new generation you would have to redo the coloration of the cells. To make my question more understandable; if you had a culture of bacteria that had a successful/working version of this system and each cell picked one out of say 5 colors to express, every neighboring cell would have more or less a different color.

[Salva Duran]

There are different versions of brainbow and, if I recall correctly, there is at least one that involves inversions of DNA not excisions (so there is no loss of information). Cutting it short , you need to control the cre expression with a promoter that only activates during division. This way you force to rearrange DNA in the division events and the color should stay the same for as long as the cell doesnt divide.

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[Kevin C. Ma]

I agree - I think recombinases are the way to do it. You may want to also check out papers from the Lu Lab and the Endy Lab where they used recombinases to construct logic gates: https://microbiology.okstate.edu/faculty/prade/rprade/MICR4263P2_files/SB%20p4.pdf

Specifically they used unidirectional ones, so the issue with Cre (repeated inversion) as Salva suggested wouldn't be a problem - after an initial "population splitting" event, the various sub-populations are locked into a single state. There are clever ways to go about arranging recombination sites which will give you a desired result. As is done in Brainbow (I think) you can have multiple sets of recombination sites, some of which may be excised leading to a fluorescent protein (or a combination of fluorescent proteins) being expressed. Another interesting approach is to overlay these sites which may give you more control over which states or sequences of states you might want to have....

[Nathan McCorkle]

You might also check out the mechanisms of mosaicism that already
exist in day to day life, like with barr bodies:
https://en.wikipedia.org/wiki/Barr_body
https://en.wikipedia.org/wiki/X-inactivation

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