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Author Topic:   Random DNA Sequences Contain Information
Taq
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Message 1 of 18 (815386)
07-19-2017 4:48 PM


What are the chances that a random DNA sequence will have beneficial function, and therefore information? A lot better than you may think.

A team of researches inserted random DNA sequences into E. coli and then tested to see if those random DNA sequences increased fitness. To their surprise, 25% of the random DNA sequences were beneficial as either RNA molecules or as proteins.

quote:
Random sequences are an abundant source of bioactive RNAs or peptides

Rafik Neme, Cristina Amador, Burcin Yildirim, Ellen McConnell & Diethard Tautz

Nature Ecology & Evolution 1, Article number: 0127 (2017)

http://www.nature.com/articles/s41559-017-0127?WT.mc_id=C...

It 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.


Not only is information present in random DNA sequences, it is very common. This counters the ID claim that information can only come about if an intelligence puts it there.

Preferred forum: Biological Evolution


Replies to this message:
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AdminNosy
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Message 2 of 18 (815388)
07-19-2017 4:55 PM


Thread Copied from Proposed New Topics Forum
Thread copied here from the Random DNA Sequences Contain Information thread in the Proposed New Topics forum.
  
jar
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From: Texas!!
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Message 3 of 18 (815389)
07-19-2017 5:34 PM


Game, Set, Match.

My Sister's Website: Rose Hill Studios     My Website: My Website

  
RAZD
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Message 4 of 18 (815447)
07-20-2017 9:50 AM
Reply to: Message 1 by Taq
07-19-2017 4:48 PM


A team of researches inserted random DNA sequences into E. coli and then tested to see if those random DNA sequences increased fitness. To their surprise, 25% of the random DNA sequences were beneficial as either RNA molecules or as proteins.

25% beneficial
52% detrimental
23% neutral

Fascinating eh?

Enjoy


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This message is a reply to:
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AnswersInGenitals
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Message 5 of 18 (815516)
07-20-2017 5:21 PM
Reply to: Message 1 by Taq
07-19-2017 4:48 PM


If You Can Raed Tihs, You Msut Be Raelly Smrat
"Aoccdrnig to a rscheearch at Cmabrigde Uinervtisy, it deosn't mttaer in waht oredr the ltteers in a wrod are, the olny iprmoatnt tihng is taht the frist and lsat ltteers be at the rghit pclae. The rset can be a toatl mses and you can sitll raed it wouthit porbelm. Tihs is bcuseae the huamn mnid deos not raed ervey lteter by istlef, but the wrod as a wlohe."

From this rather dated article: http://www.foxnews.com/...aed-tihs-msut-be-raelly-smrat.html

Written language (as well as spoken language, but it’s much harder to demonstrate) can suffer a great many “mutations” without any loss of information. This is primarily due to its being highly redundant. This redundancy makes it very robust in the face of errors which is very important since language is a basic form of communication and can be essential for survival.

A species genome is also essential for survival and must therefore be very robust in the face of all sorts of insults that result in changes. One form of this robustness is an elaborate (but mechanistically simple) edit and repair process. But for a second form it would be surprising if genomes are not highly redundant and able to incur extensive changes without compromising the viability of the organism/species.

So maybe it’s not so surprising that random sequences of bases can yield useful dna since, in a real sense, the original dna is highly random to start with and only a few key elements have to be maintained. This is shown in the molecular homology maps of proteins, which compare the amino acid sequences for proteins from different species that perform the same function. These sequences can vary widely and even be of different lengths with only a few short regions (that interact with the ligands the protein contacts) being very similar.

This robustness through redundancy also applies to our bodies as a whole and well engineered products. (As an example, the solid-state-drive of the computer I’m typing this on has 20% spare memory).


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caffeine
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From: Prague, Czech Republic
Joined: 10-22-2008
Member Rating: 2.3


Message 6 of 18 (815606)
07-21-2017 3:16 PM
Reply to: Message 5 by AnswersInGenitals
07-20-2017 5:21 PM


Re: If You Can Raed Tihs, You Msut Be Raelly Smrat
These results still seem surprising to me. Robustness through redundancy is the reason people always say most mutations are neutral with respect to fitness. Due to the redundancies in the genetic code, a lot of mutations don't have any phenotypic effect.

In this case they're not just claiming their random variants were harmless due to inbuilt redundancies - a quarter of them were actually fitter than the originals. That's surprising to me.


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Taq
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Posts: 7190
Joined: 03-06-2009
Member Rating: 3.2


Message 7 of 18 (815607)
07-21-2017 3:19 PM
Reply to: Message 6 by caffeine
07-21-2017 3:16 PM


Re: If You Can Raed Tihs, You Msut Be Raelly Smrat
caffeine writes:

In this case they're not just claiming their random variants were harmless due to inbuilt redundancies - a quarter of them were actually fitter than the originals.

There are no "originals" in this experiment since they are random 150 base pair DNA segments bookended by a promoter and terminator.


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caffeine
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Posts: 1346
From: Prague, Czech Republic
Joined: 10-22-2008
Member Rating: 2.3


Message 8 of 18 (815608)
07-21-2017 3:25 PM
Reply to: Message 7 by Taq
07-21-2017 3:19 PM


Re: If You Can Raed Tihs, You Msut Be Raelly Smrat
There are no "originals" in this experiment since they are random 150 base pair DNA segments bookended by a promoter and terminator.

I thought these were inserted into bacterial genomes and then the resulting bacteria competed against wild-type individuals. Did I misunderstand the abstract?


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Taq
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Posts: 7190
Joined: 03-06-2009
Member Rating: 3.2


Message 9 of 18 (815610)
07-21-2017 3:32 PM
Reply to: Message 8 by caffeine
07-21-2017 3:25 PM


Re: If You Can Raed Tihs, You Msut Be Raelly Smrat
caffeine writes:

I thought these were inserted into bacterial genomes and then the resulting bacteria competed against wild-type individuals. Did I misunderstand the abstract?

I think I misunderstood your post. I thought you were saying that the test group of E. coli had modified versions of genes (i.e. redundancies) found in the parent population.


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Dr Jack
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Posts: 3506
From: Leicester, England
Joined: 07-14-2003


(1)
Message 10 of 18 (815647)
07-22-2017 9:58 AM
Reply to: Message 1 by Taq
07-19-2017 4:48 PM


For want of a good negative control
I am... unconvinced.

Their claims are based around an experiment in which they either have an empty expression vector or a random sequence of 150bp inserted into the vector. The 25% beneficial claim comes from those that perform better than the empty vector but the empty vector is not a true negative control; rather it still contains the FLAG tag so rather than comparing whether random sequences are beneficial per se, it is really comparing whether they are better or worse than having a different sequence before the FLAG tag is better or worse than having the FLAG tag alone. Also, I can see no evidence that they controlled for plasmid copy number, and I think the plasmid they're using can have variable copy number.

I find it particularly telling that only a single sequence performed less well when a stop codon was inserted at the start of the sequence.

Edited by Dr Jack, : No reason given.


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Dr Jack
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Posts: 3506
From: Leicester, England
Joined: 07-14-2003


Message 11 of 18 (815648)
07-22-2017 10:00 AM
Reply to: Message 8 by caffeine
07-21-2017 3:25 PM


Re: If You Can Raed Tihs, You Msut Be Raelly Smrat
I thought these were inserted into bacterial genomes and then the resulting bacteria competed against wild-type individuals. Did I misunderstand the abstract?

Yes, you have. The sequences were cloned into an expression plasmid and so the sequence is carried in an extra-chromosomal plasmid rather than inserted into the genome.


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Taq
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Posts: 7190
Joined: 03-06-2009
Member Rating: 3.2


Message 12 of 18 (815811)
07-24-2017 4:12 PM
Reply to: Message 10 by Dr Jack
07-22-2017 9:58 AM


Re: For want of a good negative control
Dr Jack writes:

The 25% beneficial claim comes from those that perform better than the empty vector but the empty vector is not a true negative control; rather it still contains the FLAG tag so rather than comparing whether random sequences are beneficial per se, it is really comparing whether they are better or worse than having a different sequence before the FLAG tag is better or worse than having the FLAG tag alone. Also, I can see no evidence that they controlled for plasmid copy number, and I think the plasmid they're using can have variable copy number.

I would think that an increase in fitness between a FLAG tag and a FLAG fusion protein (or RNA molecule) would indicate that the added 150 base pairs is responsible for the increase in fitness.

As to copy number, it would appear to be a pretty standard expression vector which would have multiple copies and very high induced expression. My criticism is that the introduced gene may make up a disproportionate percentage of total RNA or total protein.

As to stop codons, the gene could still have activity as an RNA gene, so I don't see too much trouble with the translated peptide not having activity.


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Dr Jack
Member
Posts: 3506
From: Leicester, England
Joined: 07-14-2003


Message 13 of 18 (815865)
07-25-2017 4:01 PM
Reply to: Message 12 by Taq
07-24-2017 4:12 PM


Re: For want of a good negative control
I would think that an increase in fitness between a FLAG tag and a FLAG fusion protein (or RNA molecule) would indicate that the added 150 base pairs is responsible for the increase in fitness.

It does indicate an increase in fitness, but it does not indicate that the random DNA sequence is coding for anything of consequence. They want to argue that the sequences they've introduced are doing something of consequence. I think the more obvious interpretation is that they are not doing anything in, and of, themselves but rather preventing a harmful effect.

As to copy number, it would appear to be a pretty standard expression vector which would have multiple copies and very high induced expression. My criticism is that the introduced gene may make up a disproportionate percentage of total RNA or total protein.

Quite. But they measure (organism) fitness using the proxy of the number of copies of the plasmid in their population; if the plasmid varies systematically in copy number that will bias their results.

As to stop codons, the gene could still have activity as an RNA gene, so I don't see too much trouble with the translated peptide not having activity.

RNA can certainly have activity; however the majority of active sequences in the body are protein coding. If you're claiming that you have hundreds of beneficial sequences but only one is influenced by the STOP codon that implies a ratio of active protein sequences to RNA sequences I find implausible.


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Taq
Member
Posts: 7190
Joined: 03-06-2009
Member Rating: 3.2


(1)
Message 14 of 18 (815875)
07-25-2017 7:04 PM
Reply to: Message 13 by Dr Jack
07-25-2017 4:01 PM


Re: For want of a good negative control
Dr Jack writes:

It does indicate an increase in fitness, but it does not indicate that the random DNA sequence is coding for anything of consequence. They want to argue that the sequences they've introduced are doing something of consequence. I think the more obvious interpretation is that they are not doing anything in, and of, themselves but rather preventing a harmful effect.

That is a fair criticism. It would be much more helpful if they moved these genes into the bacterial chromosome so they could compare fitness to the wild type strain, and especially so for the FLAG-only version of the gene. It certainly wouldn't be feasible for the thousands of random sequences in their library, but they could have at least done this with their control plasmid.

Quite. But they measure (organism) fitness using the proxy of the number of copies of the plasmid in their population; if the plasmid varies systematically in copy number that will bias their results.

A very good point. In my own experience, plasmid stability can vary quite a bit due to different inserts in the same plasmid.


RNA can certainly have activity; however the majority of active sequences in the body are protein coding. If you're claiming that you have hundreds of beneficial sequences but only one is influenced by the STOP codon that implies a ratio of active protein sequences to RNA sequences I find implausible.

From my reading, they only tested 3 clones individually, 2 of which were not affected by the insertion of a stop codon. From the paper:

"Although two of our three individually tested clones suggest that the RNA function could be more important than the protein function, this constitutes at present only a small sample and may not be indicative of the true ratio between RNA and peptide functions."


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Dr Jack
Member
Posts: 3506
From: Leicester, England
Joined: 07-14-2003


Message 15 of 18 (815929)
07-26-2017 12:57 PM
Reply to: Message 14 by Taq
07-25-2017 7:04 PM


Re: For want of a good negative control
Ah, I misunderstood and thought they'd tested more than that. My bad.
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