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So non-protein coding DNA is now “widely recognized” to be not junk?

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Here.

Special Issue on microRNAs – the smallest RNA regulators of gene expression

It is now well recognised that the majority of non-protein-coding genomic DNA is not “junk” but specifies a range of regulatory RNA molecules which finely tune protein expression. This issue of CDD contains an editorial and 5 reviews on a particular class of these regulatory RNAs, the microRNAs (miRs) of around 22 nucleotides, and which exert their effects by binding to consensus sites in the 3’UTRs of mRNAs. The reviews cover the role of miRs from their early association with CLL to other forms of cancer, their importance in the development of the epidermis and their potential as disease biomarkers as secreted in exosomes. In addition, we publish a News and Commentary on CRISPR, a technology which is not only revolutionising genetic manipulation in the lab, but which has the potential to treat genetic disease in vivo.

Oh? Does anyone remember when BioLogos founder Francis Collins was fronting “junk DNA”? So we were all suppose to rush to believe that. But hey, now we aren’t.

Comments
Different parts of the functional subset of our DNA have different functions. For instance, a ribosomal RNA forms part of the ribosome, and thus facilitates the expression of protein-coding genes. Typically, we consider "functional sequences" to be those that contribute to some part of the organism's normal activities. A 50 million year old broken transposon almost certainly doesn't do that, a ribosomal RNA does. Before you embark on some philosophical exploration of the word "function", I'd remind you any argument as the the amount of junk DNA requires a definition of biological funciotn.wd400
December 10, 2014
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Oh don't all of a sudden be coy now wd400. You're the one who is making the argument. wd400 @ 30:
Is most of the genome functional, or is biological function restricted to tiny islands of sequence space?
By "most of the genome" do you mean DNA? Will it help you if I ask you "what is the function of the genome"? What if the question you pose is a false dichotomy? wd400 @ 30:
Given how mutations we each have it can’t be both.
Sure it can. wd400 @ 47:
That’s not why junk DNA exist, because mutation rates are pre-site and not per-replication you can’t have a “scratch pad”. But the fact we have ~50 mutations but are not dead is strong evidence that much of our genomes are junk.
Well there you have it. You're talking about DNA. When you say DNA you mean genome and when you say genome you mean DNA. So why is it so hard to understand what I asked? wd400 @ 47:
The other possibility is that biological function are easy to come by in sequence space.
Or you could be equivocating and presenting a false dichotomy. wd400 @ 61:
If every base is functional, then it absolutely is the absolute number that matters.
Every base in DNA? What is the "function" of a base in DNA? wd400 @ 61:
We know some mutations are damaging, but most of us aren’t dead. If we each had 50 mutations in a genome completely full of function it’s hard to see how we could survive.
A genome "completely full of function"? What does that even mean? wd400 @ 63:
Yeah, so the only way out for non-junkers is to claim that biological functions are not restricted to small islands of sequence space. But that’s not exactly the standard ID/Creationist position…
Again I ask you, what is the biological function of DNA? What's so difficult about that? It seems to comprise a large part of your argument, so you must know what you're talking about. wd400 @ 66:
If those bases are functional, then function must be very easy to come by because it looks like any old sequence will do it.
What is the function of a base in DNA? wd400 @ 69:
Evolutionary conservred non-coding DNA adds up to less than 10% of the genome. Repeats get co-opted into functional sequences of course, but they weren’t functional before they copied themselves into the new structure.
See, you're talking about DNA. And equating it with the genome. DNA which is composed ob sequences of bases. the function of which, or lack thereof, is crucial to your argument. So again I ask, what is the function that you're referring to? If you can't say, then you really don't have an argument. So you don't understand the question and I don't understand how you can not understand the question. All through this thread you've been making an argument about DNA/GENOME/BASES and their FUNCTION. So I ask what is their function. Does that help? wd400 @ 74:
...are you quibbling about a precise meaning or do have a substantive point to make?
Am I quibbling about a precise meaning of function? Hardly. Let me try again. You claim the genome/DNA/a base [as far as I can tell you you use these terms interchangeably in this thread] have or do not have a function. For those that have a function, what is their function? For those that do not, what function do they lack? Your argument is that this as yet unidentified and unspecified function is easily found.
If those bases are functional, then function must be very easy to come by because it looks like any old sequence will do it.
What does it even mean to say that a base is functional or to deny that a base is functional? When you say that function must be easy to come by what do you mean? It's your argument. When you say FUNCTION what do you mean?Mung
December 10, 2014
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I don't understand the question Mung -- are you quibbling about a precise meaning or do have a substantive point to make?wd400
December 10, 2014
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wd400, just what do you think the function of DNA consists of? What does it do?Mung
December 10, 2014
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Unless their function was exactly to help generating the new functional structures. And we are back to the fact you can't maintain something for future use without having it be subject to the deleterious effects of mutation. Unless you think mutations are directed, in which case you have a fresh set of evidence against you.wd400
December 10, 2014
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drc466:
Personally – if someone told me that even just 2% of my DNA was “non-functional” or “neutral” mutations, and offered to excise that portion for me? I’d pass.
Ha! Ain't that the truth! I'll just hang onto my "junk" DNA if it's all the same to you.Phinehas
December 10, 2014
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wd400: "Repeats get co-opted into functional sequences of course, but they weren’t functional before they copied themselves into the new structure." Unless their function was exactly to help generating the new functional structures.gpuccio
December 10, 2014
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Evolutionary conservred non-coding DNA adds up to less than 10% of the genome. Repeats get co-opted into functional sequences of course, but they weren't functional before they copied themselves into the new structure.wd400
December 10, 2014
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wd400: From the above paper, about repeats:
The repeats have amended the genome by reorganizing it, creating entirely new genes and revising and rearranging the existing genes. Contrary to the earlier common assumption that insertion of repetitive elements into genes would impair the protein’s ability to function, a surprisingly large number of these elements are found in translated proteins also. The repetitive elements seem to insert into non coding regions of a gene and be incorporated into protein through alternative splicing. Since the elements contain splicing sites, new proteins may be created as a result of the shuf?ing, elongation or truncation of coding regions of the old gene. Thus, the location and distribution of the human repetitive elements may provide insight into their role in gene evolution and species differentiation.
gpuccio
December 10, 2014
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wd400: Evolutionarily Conserved Noncoding DNA http://www.els.net/WileyCDA/ElsArticle/refId-a0006126.html Abstract:
Abstract Noncoding deoxyribonucleic acid (DNA), which includes all sequences within the genome except exon sequences that encode the protein?reading frames, harbours a wide variety of regulatory genomic features and elements. The availability of increasingly complete and accurate genomic sequence data from evolutionarily separated species – as well as diverse strain and ethnic variants within species – is providing an unprecedented opportunity to identify potentially functional regions within the genomic noncoding DNA. A variety of computational approaches enable genome?wide detection, characterisation and visualisation of highly conserved sequences and the occurrence of potentially functional elements within both the conserved and evolved elements. As a result of the continued discovery of these functional elements, the nongenic genetic neighbourhoods are now considered as keys to identifying regulatory elements that are essential for gene and chromosomal function. In this article is given an overview of the various known components of the noncoding DNA landscape and present some of the bioinformatic?based approaches and resources to identify and analyse the potential regulatory regions in genomic sequences. Key Concepts: An indeterminate fraction of the noncoding proportion of the human genome has a decisive role in regulating gene expression. Comparisons among genome sequences are keys to identifying the functional regions of noncoding DNA. Identifying and analysing ‘phylogenetic footprints’ is a standard approach to examine for potential regulatory regions. Two common features of long?range regulatory elements are that they are frequently conserved in other mammals and are unique within the human genome. It is not only the conservation of the noncoding DNA but also the loss of the same that holds some of the clues to understand our phenotypic complexity and diversity. Post?ENCODE, the genome is viewed as a network of collaborating RNA transcripts with many of the regulatory regions of proteins transcribed into RNA and serve as regulators (e.g., microRNAs and siRNAs).
Just an example of a recent approach.gpuccio
December 10, 2014
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If we did not understand the way that genes code for proteins, we would not understand why synonymous mutations are well tolerated in that kind of sequence.
But we'd see very clearly that some positions could chagne, and others were conserved, within populations and between spcies. There is no such conservation, within or between, for the vast majority of human genome. If those bases are functional, then function must be very easy to come by because it looks like any old sequence will do it.wd400
December 10, 2014
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wd400: "Yeah, so the only way out for non-junkers is to claim that biological functions are not restricted to small islands of sequence space. But that’s not exactly the standard ID/Creationist position…" It seems that you are the only one to see that point. Functional islands are small and rare. That does not mean that they cannot present engineered variation, or that they cannot be rather robust to limited random error. Synonymous mutations are neutral in protein coding genes. What is the reason for that neutrality? The redundancy of the genetic code, a specific property of the coding sequences. If we did not understand the way that genes code for proteins, we would not understand why synonymous mutations are well tolerated in that kind of sequence. In the same way, if we do not understand the functional role of non coding genes, we cannot understand what kind of variation they can tolerate, or not tolerate. And we cannot understand what kind of variation is functionally engineered to provide functional diversity. Diversity can in itself be a functional goal. We have many examples of that in human engineering and in human creations, including art.gpuccio
December 10, 2014
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I would be surprised if any of DNA was functional.Mung
December 10, 2014
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Why? Only rarely functional mutations are incompatible with life, even in protein coding genes. Then why is there so little diversity in protein-coding sequences compared with introns? And you always avoid the problem that there is functional diversity. All humans are not the same, We are not the same as chimps. And so on. Yeah, so the only way out for non-junkers is to claim that biological functions are not restricted to small islands of sequence space. But that's not exactly the standard ID/Creationist position...wd400
December 10, 2014
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wd400: "I would be surprised if more than about 20% of genome was functional at the sequence level." You will be surprised. "We know some mutations are damaging, but most of us aren’t dead. If we each had 50 mutations in a genome completely full of function it’s hard to see how we could survive." Why? Only rarely functional mutations are incompatible with life, even in protein coding genes. And you always avoid the problem that there is functional diversity. All humans are not the same, We are not the same as chimps. And so on. Life and death are not the only things in the game.gpuccio
December 10, 2014
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drc466, If every base is functional, then it absolutely is the absolute number that matters.
And we know that this (tiny) percentage of mutations IS damaging – hence the well-known deleterious impacts of in-breeding, for example. Or the many known damaging defects of chromosomal mutations. To your point – if so much of our DNA is junk, why does it take so little mutation (relatively) to cause bad things? The fairly obvious logical conclusion is that our DNA isn’t mostly junk.
We know some mutations are damaging, but most of us aren't dead. If we each had 50 mutations in a genome completely full of function it's hard to see how we could survive. (FWIW, using 50 mutations as a rough number we end up with 50 mutations * 3% protein-coding * 3/4 non-synonymous ~ 1 protein-coding mutation per live birth). All of your proposed work-arounds require some sort of redundancy to shield mutated sequences from the effects of their mutation. But that doesn't work. Being sheilded from the effects of mutation means those sequences are shielded from purifying selection, the mutations they accrue will gradually spread through the population and the "back up" will no longer work. I would be surprised if more than about 20% of genome was functional at the sequence level.wd400
December 10, 2014
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wd400, You ask some decent questions regarding mutations in our DNA, but the questions are based on an invalid premise - that our DNA is not designed, and especially not superlatively designed. First of all, consider the relative amount of mutation before stuff breaks, not the absolute. While there may be a large number of mutations in every person's DNA, as a percentage of the DNA the number is pretty small - smaller than, say, the % difference between a human and a chimp (wink). And we know that this (tiny) percentage of mutations IS damaging - hence the well-known deleterious impacts of in-breeding, for example. Or the many known damaging defects of chromosomal mutations. To your point - if so much of our DNA is junk, why does it take so little mutation (relatively) to cause bad things? The fairly obvious logical conclusion is that our DNA isn't mostly junk. So, if we thus assume that the clear majority of our genome is functional in some manner, how can we have so many mutations (numerically) without obvious deleterious effects? If we take the approach of assuming the DNA is designed, there are some pretty simple possibilities: 1) Some sections are not always "On"/Used. We know that some areas of DNA are only active under certain environmental stimuli. If mutations occur in a section of code that is not "mission-critical" to daily operation, it may not present itself as damaging. By analogy, think of a congenital heart defect that only causes problems in professional athletes. 2) Over-design. Using the same congenital heart-defect analogy - if the DNA was designed to be robust in its production, genetic defects can be "hidden" by the excess or "safeties" built in to the final product. Many people are unaware that one of their two bilateral organs is "defective" for most/all of their lives. 3) Redundant Systems. Staying with the bilateral organ example - if we assume designed DNA, it is very likely that redundancy is built in to the DNA. Experiments with eyeless fruit-flies suggest that they can re-gain sight over multiple generations of interbreeding - in turn suggesting that there is some kind of "eye backup" built in to fruit-fly DNA that can fix a busted eye gene. Consider that your DNA may be like a RAID array - multiple mutations across redundant data only causes issues when it shows up in both copies (another reason not to in-breed!) Personally - if someone told me that even just 2% of my DNA was "non-functional" or "neutral" mutations, and offered to excise that portion for me? I'd pass.drc466
December 10, 2014
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Querius: Obviously, evolutionary science is now done by consensus ... No, but Dionisio brought up hardworking scientists, so we thought he considered them a valid authority. Dionisio: Where did I write that they debunked any theory? So your scientific friends didn't express an opinion on evolution, it's not their area of expertise, but did say there are unanswered questions. Sounds reasonable. Not sure why you brought it up. Dionisio: What historical events are you talking about? Turns out that there has been life on Earth for billions of years, and life today is not like life of yesteryears. http://static.guim.co.uk/sys-images/Guardian/Pix/pictures/2009/2/5/1233857620698/Archaeopteryx-fossil-001.jpg Dionisio: I simply requested a description of any hypothetical processes that could have brought us here. That's an historical question, obviously. The basic process is branching descent with modification. Adaptation is guided by natural selection.Zachriel
December 10, 2014
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@57 bw Agree, it is very interesting. Thank you for sharing it here.Dionisio
December 10, 2014
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Read this a few weeks ago and thought I would share as it is on topic: No junk: Long RNA mimics DNA, restrains hormone responses Excerpt: "Unlike many genes scientists are familiar with, GAS5 does not encode a protein. It gets transcribed into RNA, like other genes, but with GAS5 the RNA is what's important, not the protein. The RNA accumulates in cells subjected to stress and soaks up steroid hormone receptors, preventing them from binding DNA and turning genes on and off." Also: "There are thousands of long non-coding RNAs that play critical roles in gene regulation, and little data to tell us how they are functioning or where they came from," says lead author graduate student Will Hudson. "We took a deep dive into looking at the interaction of the Gas5 RNA with steroid hormone receptors, and we think this work may serve as a model to understand how lincRNAs interact with other proteins." Interesting stuff.bw
December 10, 2014
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Zachriel @40
there are plenty of unanswered questions when determining historical events.
What historical events are you talking about? My questions were about biology, not history. I simply requested a description of any hypothetical processes that could have brought us here. Signaling pathways, regulatory networks and the whole nine yard. That's all, buddy. Leave history alone. Think pure science. Just biochemistry, biology, physics. They couldn't provide any or point to any document that could explain it. They just claimed that's not their area of interest. They work on stem cell research, etc. No time for entertainment or speculative discussions. Got it now?Dionisio
December 9, 2014
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Zachriel Apparently your comrades and fellow travelers have come to give you a hand (@42, 50, 52). Now I understand why you wrote 'we' in lieu of 'I'. Ciao! :)Dionisio
December 9, 2014
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@40 Zachriel
there are plenty of unanswered questions when determining historical events.
What historical events are you talking about? My questions were about biology, not history. I simply requested a description of any hypothetical processes that could have brought us here. Signaling pathways, regulatory networks and the whole nine yard. That's all, buddy. Leave history alone. Think pure science. Just biochemistry, biology, physics. They couldn't provide any or point to any document that could explain it. They just claimed that's not their area of interest. They work on stem cell research, etc. No time for entertainment or speculative discussions. Got it now?Dionisio
December 9, 2014
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@33 Zachriel
We pointed out that nearly all of those hardworking biologists support evolutionary theory.
why did you write “We” instead of “I” in the above quoted sentence? Are you one person or a group of people?Dionisio
December 9, 2014
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"My questions were about biology, not history. I simply requested a description of any hypothetical processes that could have brought us here." Oh, Dio. You've never heard of "natural history" have you?AVS
December 9, 2014
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@40 Zachriel
there are plenty of unanswered questions when determining historical events.
What historical events are you talking about? My questions were about biology, not history. I simply requested a description of any hypothetical processes that could have brought us here. Signaling pathways, regulatory networks and the whole nine yard. That's all, buddy. Leave history alone. Think pure science. Just biochemistry, biology, physics. They couldn't provide any or point to any document that could explain it. They just claimed that's not their area of interest. They work on stem cell research, etc. No time for entertainment or speculative discussions. Got it now?Dionisio
December 9, 2014
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Dionisio, to Zachriel:
why did you write “We” instead of “I” in the above quoted sentence? Are you one person or a group of people?
I explained that to tjguy on another thread:
tjguy to Zachriel,
Who in the world are you talking about when you say “As WE said,….” We?????
His name is Legion, for he is many.
keith s
December 9, 2014
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Dionisio to Zacky:
why did you write “We” instead of “I” in the above quoted sentence? Are you one person or a group of people?
He's been doing this for a while. It's an "us vs. them" thing for Zacky.Mapou
December 9, 2014
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@40 Zachriel
We’d be happy to look at their published research debunking evolutionary theory.
Do you have reading comprehension problems? Where did I write that they debunked any theory?Dionisio
December 9, 2014
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Secondly, if all DNA were functional, then any mutations would most likely be deleterious. You need non-coding DNA to serve both as a scratch pad and a buffer against excessive changes.
That's not why junk DNA exist, because mutation rates are pre-site and not per-replication you can't have a "scratch pad". But the fact we have ~50 mutations but are not dead is strong evidence that much of our genomes are junk. The other possibility is that biological function are easy to come by in sequence space.wd400
December 9, 2014
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