mutation probability distribution

[anybody_mcc]

A question i was thinking about : Do you know if cell can change that distribution ? If so is there any known mechanism ?
And is mutation probability the same for all "letters" ?

[Son of the Suns]

I'm not sure I know what you are trying to say. Perhaps a difference in the language is the problem.

[anybody_mcc]

ok , maybe
i will try once more.
There is some probability that in given time one nucleotide will change into another ( for example A->G )
1) Are living cells able to change those probabilities. Of course by their own action , not because of outside conditions.
2) If so is there any known mechanism ?
3) Are those probabilities equal for all nucleotids in the DNA ?

[Admiral Valdemar]

I assume you're talking about gene repair, in which case, the modern eukaryotic cell has a whole suite of repair mechanisms that proof-read the DNA or related precursors and activate other mechanisms that correct any damage (within certain limits). These safeguards apply to all bases equally since a damaged base from an inversion or deletion type mutation of any type is still a threat.

The main ones off the top of my head are:

-Excision repair which broken down further produces Base Excision Repair (BER), Mismatch Excision Repair (MMR) and Nucleotide Excision Repair (NER).

-Direct chemical reversal.

All of these systems have varying degrees of accuracy, to detail everything about their working would require a dissertation here, but it is safe to summarise that a range of error rates exist in the cell DNA repair suite. Despite the modern hype over cancer, it is actually rare to develop given our cell functions are working correctly (p53 is the "guardian of the genome", a gene that controls the repair or die decision of the cell). So long as the cell can detect damage (cancer typically occurs as a stealthy disease to the body) it can eithe a) repair it, or if the damage is too far gone, b) activate the apoptosis pathway and kill that cell, making sure it doesn't become cancerous.

I hope that answered the questions, I believe that is what you wanted.

[tharkûn]

1. How are you defining "outside conditions" and "their own action"? It is well known that cells respond to stimuli by activating genes, some of which can change mutation rates (this is most obvious when dealing with upregulating or downregulating the transcription of repair enzymes). Cells, of course, are not intelligent in the traditional definition so they don't "choose" to say downregulate mismatch repair enzymes in response to starvation, that is just the way they are wired. However not all cells wired the same and what is a typical mutagenic response to starvation in one cell line is not in another.

2. Many. Would you like names or descriptions?

3. No. First certain errors are more likely simply due to chemistry. As the nucleotides come in two distinct sizes there is a different entropy and enthalpy for the mutation reaction changing a purine into a pyramidine is vastly different in terms of chemical kinetics than changing a purine into the other purine. Likewise damage to the DNA strand is different for different nucleotide sequences (famously thyamine dimers form more readily as a result of UV damage than other polymerase blocking reactions). On top of all that you have the fact that DNA has segments bound to macromolecules with different local chemical environements (i.e. Zn fingers) and spends differing amounts of time in an non-based paired structure (making the nucleotides more reactive).

In an nutshell certain types of mutation are more common than others. Certain loci in the genome are more likely to mutate than others as well.

[Trytostaydead]

I'm not sure about changing nucleotides, but incorporating foreign DNA, yes.

[anybody_mcc]

Thanks for the info.
To Admiral Valdemar : well the gene repair wasn't exactly what i wanted to know , but my fault. It was something like this in particular : can let's say bacterial cells increase the probability of mutation ( by , for example , switching off gene repair mechanisms ) when they encounter some new antibiotic , or whatever else that is dangerous to them and they didn't develop the resistance yet. Because in these conditions it increases chances of finding resistance to that threat , so it would be quite a nice evolutionary advantage.
And the reason i'm asking is that i read something like that , but the source wasn't too reliable.

To tharkun :
1. I understand that they don't "choose" and i'm of course asking about DNA-coded mechanism. I hope that my answer to Admiral Valdemar above makes it more clear why i'm asking.
3. Thanks very much that answers it.

[tharkûn]

was something like this in particular : can let's say bacterial cells increase the probability of mutation ( by , for example , switching off gene repair mechanisms ) when they encounter some new antibiotic , or whatever else that is dangerous to them and they didn't develop the resistance yet.

Only if antibiotic sets off a prexisting signal transduction pathway that is mutagenic. Depending on the strain of bacteria, the pharmokinetics of the antibiotic in question, and some other issues - it is possible. Earlier this summer a team showed that if you inhibited an SOS pathway in bacteria they became unable to develop resistence in the expected timeframe to both ciprofloxacin and rifampicin. That was in one of the peer reviewed journals out lab reads so it is both legit and current.

Not all bacteria will exhibit this phenomena, some strains do not have these pathways (the ones that come immediately to mind are knockout strains). Other substances are so potent they simply kill the suckers before they replicate their new more error prone DNA.

1. I understand that they don't "choose" and i'm of course asking about DNA-coded mechanism. I hope that my answer to Admiral Valdemar above makes it more clear why i'm asking.

The short answer is yes. There are pathways in some cells that will increase the mutation rate (normally through upregulating error prone polymerases or downregulating repair mechanisms).

[anybody_mcc]

Thanks very much

[Admiral Valdemar]

The nuceotide chemical differences I should've put in instead of just assuming you were asking whether some bases were repaired unequally. They are indeed different and things like thymine dimerisation are more common when UV or similar mutagens are present, so there will be trends in which bases cause problems depending on circumstance.