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Topic: Random sequences are an abundant source of bioactive RNAs or peptides (Read 249 times) previous topic - next topic

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  • JonF
Random sequences are an abundant source of bioactive RNAs or peptides
Random sequences are an abundant source of bioactive RNAs or peptides

Quote
t is generally assumed that new genes arise through duplication and/or recombination of existing genes. The probability that a new functional gene could arise out of random non-coding DNA is so far considered to be negligible, as it seems unlikely that such an RNA or protein sequence could have an initial function that influences the fitness of an organism. Here, we have tested this question systematically, by expressing clones with random sequences in Escherichia coli and subjecting them to competitive growth. Contrary to expectations, we find that random sequences with bioactivity are not rare. In our experiments we find that up to 25% of the evaluated clones enhance the growth rate of their cells and up to 52% inhibit growth. Testing of individual clones in competition assays confirms their activity and provides an indication that their activity could be exerted by either the transcribed RNA or the translated peptide. This suggests that transcribed and translated random parts of the genome could indeed have a high potential to become functional. The results also suggest that random sequences may become an effective new source of molecules for studying cellular functions, as well as for pharmacological activity screening.
"I would never consider my evaluation of his work to be fair minded unless I had actually read his own words." - Dave Hawkins

  • nesb
Re: Random sequences are an abundant source of bioactive RNAs or peptides
Reply #1
God made all organisms perfect, and time only degrades them. Change is inherently bad.

Re: Random sequences are an abundant source of bioactive RNAs or peptides
Reply #2
As are people
Love is like a magic penny
 if you hold it tight you won't have any
if you give it away you'll have so many
they'll be rolling all over the floor

Re: Random sequences are an abundant source of bioactive RNAs or peptides
Reply #3
Wow, that's a frighteningly large percentage.

I wonder if there are any copies of that old computer code (Terra-life?) that would show similar percentages.

Re: Random sequences are an abundant source of bioactive RNAs or peptides
Reply #4
Hmm, this is indeed frigtheningly high. So high in fact I might actually not believe it. I will have to understand their methods better.

Assuming the numbers hold up, I wonder if it could be determined at what point this kind of persistent random generation of proteins could outweigh the metabolic cost of their synthesis. Could it be the case that the level of random transcription and translation we see in life today, has in some sense been "tuned" to that level by selection operating over geological time?

Biosynthesizing lots of RNA and protein during the cell cycle is costly, yet at the same time it has that potential to contribute to evolution and adaptation, so there is concievably some low level at which the detrimental effect is balanced out by the benefit of adaptation?
"At least you can fucking die and leave North Korea." - Christopher Hitchens

Re: Random sequences are an abundant source of bioactive RNAs or peptides
Reply #5
I don't have access to the paper, but if it is correct, we won't have to argue against Hoyle's fallacy of a 747 in a junkyard! :-)
Believer in High Powers, and naturally, logarithms.
Pikkiwoki is the one true god.

  • JonF
Re: Random sequences are an abundant source of bioactive RNAs or peptides
Reply #6
Where are you?  I see the entire paper and I don't have any Nature credentials.
"I would never consider my evaluation of his work to be fair minded unless I had actually read his own words." - Dave Hawkins

  • Monad
Re: Random sequences are an abundant source of bioactive RNAs or peptides
Reply #7
I think this fits facilitated variation theory nicely

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

the idea is organisms have evolved to evolve and adsorb the costs of variation through various process that leverage the benefits while reducing the risks of damage to the organism's functioning. The fact that this is in bacteria that already have a highly modular and stripped down genetic architecture (with a minimal number of core conserved processes and lots of weak linkage) and have evolved to make use of spare genetic parts exchanged through the 'cloud' using HGT pretty much continuously makes this even more understandable.
  • Last Edit: July 21, 2017, 09:52:44 AM by Monad

Re: Random sequences are an abundant source of bioactive RNAs or peptides
Reply #8

Re: Random sequences are an abundant source of bioactive RNAs or peptides
Reply #9
Where are you?  I see the entire paper and I don't have any Nature credentials.

Shit, I can see it now--thanks. It wouldn't load last time I tried.
Believer in High Powers, and naturally, logarithms.
Pikkiwoki is the one true god.

Re: Random sequences are an abundant source of bioactive RNAs or peptides
Reply #10
Turns out there are good reasons to doubt the conclusions of the paper. I find the arguments leveled here persuasive:
Gene Evolution: Getting something from nothing.

Quote
Caroline M. Weisman and Sean R. Eddy: (...) It's the finding that 25% of random sequences are beneficial that is of particular interest. It appears to suggest a high probability in the third term of the protogene equation-- but it's unexpected, because one would think that improving on an already highly adapted E. coli would be difficult. For example, beneficial mutations occur relatively rarely in quantitative longterm in vitro evolution experiments in E. coli [10]. In this regard, we think there are two important caveats to this observation.
One issue is that because the experiment measures relative (normalized) frequency changes in competitive growth conditions, the change in frequency of a sequence depends on its growth rate relative to every other random sequence in the pool. Even assuming that drift is negligible, as Neme et al. [2] argue, sequence enrichment does not mean that a sequence is beneficial relative to wildtype E. coli, only that it was better than other random sequence competitors. It could be that all the random sequences are deleterious to E. coli, but some are less deleterious than others, and these would rise to higher relative frequencies. Neme et al. [2] address this issue by choosing three individual beneficial sequences and showing that all three individually outcompete the 'empty vector'. This raises a second issue: the vector without insert is neither empty nor innocuous. The vector (pFLAG-CTC) carries strong transcription and translation signals. It drives IPTGinducible expression across its multiple cloning site, producing a 350 nucleotide RNA and a 38 amino-acid open reading frame at high levels. Neme et al. [2] do not observe these products because they assay expression by western blot with an anti-FLAG-tag antibody, but the FLAG tag in the vector without insert is out of frame by design. Because high-level expression of any exogenous plasmid-encoded sequence is detrimental to the E. coli host, under these conditions a beneficial random sequence could include anything that decreases RNA or protein expression levels relative to the vector without insert, for instance by base-pairing complementarity to the translation initiation site. Indeed, all three beneficial clones seem to show strongly reduced protein expression relative to the population average of the library.
Although we have reservations about the correctness of the conclusion of Neme et al. [2] that 25% of their random sequences have beneficial effects on E. coli growth rate, a body of work from these and other authors does suggest that each of the three terms in the protogene equation are high enough to be measurable in laboratory experiments, and thus could easily be relevant on evolutionary timescales. Franc¬łois Jacob was correct that gene duplication and divergence is a dominant force in gene evolution, but his personal intuition about the odds of new genes arising de novo may have been simply wrong. Experiments studying the transcription, translation, and functionality of random sequences are proving to be fruitful territory, replacing Jacob's intuition with experimental data
"At least you can fucking die and leave North Korea." - Christopher Hitchens

  • nesb
Re: Random sequences are an abundant source of bioactive RNAs or peptides
Reply #11
I told you.

I assume that just says I'm right.