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Posted

While gazing upon a diagram of the secondary structure of the large sub-unit of the E.Coli ribosome. I came to the conclusion that this structure seems to be nearly impervious to evolution or at least to small scale mutations.



I wondered how many base changes could occur before its performance was halted. There are scores of loops and scores of helixes. I would think many changes could occur on the loops and only cause extremely minor tertiary changes. I would also think that a number of changes could occur in the helixes and only cause a slight bump or tighter or loser twist. In the helixes double hydrogen bonded pairs could be switch around with no backlash as could triple bonded pairs. AU to UA and CG to GC. Double and triple bonded pairs could be interchanged without a noticeable effect. AU to CG. Pairs could be missing altogether and not much changes. Once this structure evolved to be nearly indestructible the true evolution of proteins could take hold.



I would think that only changes in the bases of the active sites where the rRNA bases come into contact with the bases for mRNA and tRNA could amount to anything catastrophic and any changes to the vast majority of the bases would only very slightly enhance the function or only very slightly decrease the function. Having larger loops or longer helixes causing bulges in the tertiary structure may enhance the stability of the ribosome in its fluid environment or help it attach better to the endoplasmic reticulum.



This is completely different than the sequence found on a messenger RNA where one base change changes the reading sequence of the code for a protein which many times is catastrophic.



There are a couple hundred copies of rRNA in the human genome. I wonder how much difference there can be between the different copies.



In other words is rRNA such an extremely flexible and potentially variable sequence of bases that it has become basically indestructible to small errors and mutations and it is this property that has made it probably the main thing for life.



Does anyone know of any research being done along those lines or wish to banter about it?


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Posted

I am not sure why you think ribosomes are "impervious" to evolution (I'm not even sure what that means). I will point out though that the ribosome is the target of a whole class of antibiotics and resistance to those antibiotic derives from mutations to the ribosome.

Posted

MEC1960

 

I do not mean that the ribosome does not change, it very much does so, as does everything related to DNA.

 

My point is that it seems to me that a large percentage of changes could occur (not all simultaneously) without changing the ribosome's function.

All of which I described in the original post.

I am just wondering has anyone else pursued this avenue.

 

Did its structure evolve to a point that it can absorb random mutations without the catastrophic effects found in say having a random mutation in mRNA coding for a protein? That is all I meant by impervious to evolution. Impervious to detrimental structural changes caused by random mutations.

 

Thanks for the antibiotic information.

I will see what I can find along those lines as far as what parts are being changed that results in resistance.

Well unless you know and were willing to share which would save me some time.

Posted (edited)

That is clearly not the case. In contrast to many proteins the function is extremely conserved and as consequence they have large conserved sequences (which is why they are so useful for phylogeny). If you think about it, structural RNA has less degrees of freedom than mRNA. Mutations in the mRNA may not alter the peptide sequence at all, whereas changes in the rRNA especially in unpaired regions are likely to cause alterations of the structure.

In fact, analyses have shown that the various regions (loops, stems, bulges) evolve at different rates.

Edited by CharonY
Posted

CharonY, thanks for your reply.

I guess using more appropriate terminology my question boils down to whether it is JUST the ribosome's structure that is conserved whereas the actual nucleotide base sequence can be variable.

For example I have included a more viewable section of the ribosome for discussion. Could say nucleotide #1110 be exchanged for another base and have no ill effects whereas if that occurred in mRNA could be disastrous?

The structure has not changed, thus absorbing a random mutation without consequences.

Or could base #1110 be removed completely and the overall structure would be only very slightly changed?

I guess what I am really asking is whether I am barking up a tree that has already been barked up and found empty?

I see that you say that the base sequence is conserved but is that only in the active sites and the other parts can and are changeable and can be used in phylogenic studies.

Can you steer me to a site that has comparisons of ribosome?

Is there any variability between any of the more than 200 copies found just in the human genome?

Just looking for more information. Thanks for all your help.

 

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Posted

Yes, the evolution of rDNAs is a huge topic. A lot is known from bacterial sequences (as the ones you posted) , though the amount of eukaryotes is also increasing. Just looking at the structure will tell you quite a bit. E.g. look at the stem removing one base will automatically result in an unpaired base pair. That has immediate consequences on the structure. Even exchanging the base at 1110 may change the size of the bulge (although that would be harder to predict). As the function of rRNA is very structural minor structural changes can affect the overall performance of the ribosome and its regulation.

 

The literature is incredibly rich, there are whole textbooks on this topic, heck there are whole journals dedicated to RNAs and their structure. Here just a few random papers:

 

Ali et al Nucl. Acids Res. (1999) 27 (14): 2825-2831

Smit et al. Nucl. Acids Res. 2007 May; 35(10): 3339–3354.

Kuo et al. Nucl. Acids Res. 1996 Dec 1;24(23):4817-24

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