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A "junk DNA" discussion

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  • #16
    [QUOTE=jordanriver;91855]

    If so much is conserved, maybe its because they still have a necessary function, hundreds of millions of years seems like an awful long time for "junk" to survive if there is no cost benefit.
    I'm not sure how to interpret this. Are you talking about the survival of ANY unnecessary sequences, or the survival of some specific sequences, over such long periods of time? I would think any particular sequence which survives "hundreds of millions of years", which is to say can be found in nearly every eukaryotic species, is prima facie necessary and functional, whether we know what it does or not.

    Think of a sink where the drain rate matches the faucet rate. There will always be water in the sink, but it won't be the SAME water over any longer period of time.

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    • #17
      [QUOTE=phank;91883]
      Originally posted by jordanriver View Post
      I'm not sure how to interpret this. Are you talking about the survival of ANY unnecessary sequences, or the survival of some specific sequences, over such long periods of time? I would think any particular sequence which survives "hundreds of millions of years", which is to say can be found in nearly every eukaryotic species, is prima facie necessary and functional, whether we know what it does or not.

      Think of a sink where the drain rate matches the faucet rate. There will always be water in the sink, but it won't be the SAME water over any longer period of time.
      Are the molecules of water that went down the sink, to be replaced by new molecules of water from the faucet,
      analogous to the molecules of non-functional ncRNA/ncDNA that get 'purified' away
      .ie negative selection
      To say that crony capitalism is not true/free market capitalism, is like saying a grand slam is not true baseball, or like saying scoring a touchdown is not true American football ...Stefan Mykhaylo D

      Comment


      • #18
        [QUOTE=jordanriver;91905]
        Originally posted by phank View Post
        Are the molecules of water that went down the sink, to be replaced by new molecules of water from the faucet,
        analogous to the molecules of non-functional ncRNA/ncDNA that get 'purified' away
        .ie negative selection
        And replaced by new "discarded" DNA sequences, which in turn are not conserved as a sequence. AIUI, the "sink" is slowly filling up over the course of deep time, as newly broken or repetitive sequences get replicated faster than they get discarded. Lurch surely knows vastly more than I about that.

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        • #19
          [QUOTE=phank;91967]
          Originally posted by jordanriver View Post
          And replaced by new "discarded" DNA sequences, which in turn are not conserved as a sequence. AIUI, the "sink" is slowly filling up over the course of deep time, as newly broken or repetitive sequences get replicated faster than they get discarded. Lurch surely knows vastly more than I about that.
          don't forget about the problem of population fitness, I mean, all that extra useless baggage.
          OTOH, there is such a thing as extinction.
          To say that crony capitalism is not true/free market capitalism, is like saying a grand slam is not true baseball, or like saying scoring a touchdown is not true American football ...Stefan Mykhaylo D

          Comment


          • #20
            Originally posted by jordanriver View Post
            don't forget about the problem of population fitness, I mean, all that extra useless baggage.
            OTOH, there is such a thing as extinction.
            Somehow I doubt that excess genetic baggage contributes much to extinctions. My reading is that species kind of "set up", and become resistant to genetic changes except mostly through speciation. Or maybe that populations do drift, but that the drift doesn't particularly track environmental changes.

            I'm not aware that something as low-level as cell reproduction handicaps species because there's too much "junk" in the genome. But I'm certainly not the expert on this.

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            • #21
              Originally posted by jordanriver View Post
              If so much is conserved, maybe its because they still have a necessary function, hundreds of millions of years seems like an awful long time for "junk" to survive if there is no cost benefit.
              That's just it, the sequences aren't conserved. They are accumulating mutations at a rate consistent with neutral drift. That is what the abstract I cited was focused on, how a functional DNA sequence could have every base changed without destroying function, or how mutations could never happen in these stretches of DNA, both of which seem like preposterous ideas.

              At the same time, there is really no selective pressure for removing all of the junk DNA from most genomes. The onion has a 100 billion base genome, abot 30 times the size of the human genome, and it seems to chug along just fine. Some species of amoeba have genomes nearly 200 times larger than the human genome, and they do just fine. Only in phosphorous poor environments do we see evidence of negative selection on genome sizes due to DNA having a phosphate backbone. One such species is the bladderwort which has a genome of just 80 million bases which is just 1/30th of the humane genome, and a staggering 1/1250th of the onion genome. I can't see how the onion is 1,250 times more complex than the bladderwort, can you?

              I don't know if 100% is argued for, but there is negative selection/purifying selection/, outside of conserved noncoding sequences.

              at least that's what I've read.
              Yes, and that conserved sequence is included in the 10% of the human genome that is thought to have function.

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              • #22
                Originally posted by jordanriver View Post
                don't forget about the problem of population fitness, I mean, all that extra useless baggage.
                OTOH, there is such a thing as extinction.
                You would need to show that there is a selective disadvantage to having a larger genome. How much more energy is needed to replicate billions of bases compared to the overall energy budget of the organism? I would think that the energy budget for DNA replication is extremely tiny. For example, there are proteins in your muscle cells called SERCA's that pump calcium back into intracellular compartments so that muscles will stop contracting. SERCA proteins make up about 1/4th of the dry weight of muscle cell. Everytime they pump calcium back into the sarcoplasmic reticulum it requires an ATP, the same ATP that is used to extend a single base on a DNA molecule. From my experience, a muscle cell can use up more ATP's in a simple workout than it used to make all of the DNA in that muscle cell.

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                • #23
                  Originally posted by Method View Post
                  You would need to show that there is a selective disadvantage to having a larger genome. How much more energy is needed to replicate billions of bases compared to the overall energy budget of the organism? I would think that the energy budget for DNA replication is extremely tiny. For example, there are proteins in your muscle cells called SERCA's that pump calcium back into intracellular compartments so that muscles will stop contracting. SERCA proteins make up about 1/4th of the dry weight of muscle cell. Everytime they pump calcium back into the sarcoplasmic reticulum it requires an ATP, the same ATP that is used to extend a single base on a DNA molecule. From my experience, a muscle cell can use up more ATP's in a simple workout than it used to make all of the DNA in that muscle cell.
                  your reasoning sounds logical.
                  but so were papers from Nature and GenomeBiology, which seemed to be using incredulity arguments (me guilty too)
                  Transposons, or Jumping Genes: Not Junk DNA?
                  " The fact that the V-SINEs are so highly conserved suggests that, even though their true function is still unknown, these TEs must have some specific role. If not, then why do so many different species share the same, or similar, V-SINEs? Over 500 million years is a long time for "junk" to survive if it has no purpose."
                  http://www.nature.com/scitable/topic...-junk-dna-1211
                  Regulatory RNAs and the demise of 'junk' DNA
                  "These observations of low-level, regulated transcription across much of the mammalian genome demonstrate that much more RNA is being generated in our cells than we previously thought. With the mounting evidence of large amounts of transcription, the question becomes: are all these transcripts functional? No one yet has the answer, but it seems hard to fathom why evolution would have selected for such extensive transcription if it were useless or wasteful.
                  http://genomebiology.com/2006/7/9/328
                  anyway, its possible my interpretation of the papers is mistaken.

                  wouldn't be the first time.
                  To say that crony capitalism is not true/free market capitalism, is like saying a grand slam is not true baseball, or like saying scoring a touchdown is not true American football ...Stefan Mykhaylo D

                  Comment


                  • #24
                    Originally posted by jordanriver View Post
                    your reasoning sounds logical.
                    but so were papers from Nature and GenomeBiology, which seemed to be using incredulity arguments (me guilty too)
                    1. Finding function for some transposable elements does not demonstrate that all transposable elements have function.

                    2. DNA that is transcribed into mRNA at very low levels is most likely due to leaky trascriptase activity and has nothing to do with the function or lack of function of that DNA. To use my analogy from ealier, low level mRNA production as an indication of function is the same as saying that your junk in the kitchen trash can has function because it releases odor molecules into the air. Just doing something is not function.

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                    • #25
                      and then there's cancer.
                      Too many papers suggesting mutated ncDNA/ncRNA is linked to cancer.

                      of course, since cancer is primarily a disease of the aged, and evolution is dispassionate, one could argue a selective advantage, selecting out those who consume resources but no longer contribute to population fitness (make babies)

                      OTOH, the cancer seems to be linked to mutated ncRNA that is known to have LOST a function, the function of suppressing cancer.
                      I admit I have not been able to find links to what happens when mutations accumulate in DNA/RNA that is not only non-coding but also non-functioning. ...I mean, its not like they were busy 'suppressing' anything important.
                      To say that crony capitalism is not true/free market capitalism, is like saying a grand slam is not true baseball, or like saying scoring a touchdown is not true American football ...Stefan Mykhaylo D

                      Comment


                      • #26
                        Originally posted by jordanriver View Post
                        and then there's cancer.
                        Too many papers suggesting mutated ncDNA/ncRNA is linked to cancer.

                        of course, since cancer is primarily a disease of the aged, and evolution is dispassionate, one could argue a selective advantage, selecting out those who consume resources but no longer contribute to population fitness (make babies)
                        Not validly. Reproduction has no clue about anything else in the universe that might be consuming resources. It happens or it doesn't.

                        OTOH, the cancer seems to be linked to mutated ncRNA that is known to have LOST a function, the function of suppressing cancer.
                        Do you have a link here?

                        I admit I have not been able to find links to what happens when mutations accumulate in DNA/RNA that is not only non-coding but also non-functioning. ...I mean, its not like they were busy 'suppressing' anything important.
                        As I understand it, there's quite a bit on this subject out there. Pseudogenes, for example. Is this what you mean?

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                        • #27
                          Originally posted by jordanriver View Post
                          and then there's cancer.
                          Too many papers suggesting mutated ncDNA/ncRNA is linked to cancer.
                          Non-coding DNA/RNA is not a synonym for junk DNA.

                          of course, since cancer is primarily a disease of the aged, and evolution is dispassionate, one could argue a selective advantage, selecting out those who consume resources but no longer contribute to population fitness (make babies)
                          OTOH, the cancer seems to be linked to mutated ncRNA that is known to have LOST a function, the function of suppressing cancer.
                          Finding non-coding RNA that has function does not mean that all non-coding RNA has function. If non-coding RNA has function then a percentage of mutations in that RNA will have a negative impact on the fitness of the individual and be selected against. Therefore, we should see a conservation of sequence in RNA molecules that have function. That is not what we see for about 90% of the human genome.

                          I admit I have not been able to find links to what happens when mutations accumulate in DNA/RNA that is not only non-coding but also non-functioning. ...I mean, its not like they were busy 'suppressing' anything important.
                          Non-coding RNA's that suppress tumor formation would have function and would show signs of conservation of sequence compared to non-functional DNA.

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                          • #28
                            Originally posted by Method View Post
                            Non-coding DNA/RNA is not a synonym for junk DNA.

                            .
                            Proposal; defining term
                            How about use only "non-functional" or "functional"
                            (even "pseudogene" can refer to functional according to Nature citation in wiki 's 'pseudogene')
                            To say that crony capitalism is not true/free market capitalism, is like saying a grand slam is not true baseball, or like saying scoring a touchdown is not true American football ...Stefan Mykhaylo D

                            Comment


                            • #29
                              jordanriver said: "OTOH, the cancer seems to be linked to mutated ncRNA that is known to have LOST a function, the function of suppressing cancer"
                              Originally posted by phank View Post
                              Do you have a link here?
                              hmmm, I thought I did on page 1, but here's a couple more or more
                              ScienceDaily
                              Sieving through 'junk' DNA reveals disease-causing genetic mutations
                              "Researchers can now identify DNA regions within non-coding DNA, the major part of the genome that is not translated into a protein, where mutations can cause diseases such as cancer.

                              Their approach reveals many potential genetic variants within non-coding DNA that drive the development of a variety of different cancers. This approach has great potential to find other disease-causing variants.

                              Unlike the coding region of the genome where our 23,000 protein-coding genes lie, the non-coding region -- which makes up 98% of our genome -- is poorly understood. Recent studies have emphasised the biological value of the non-coding regions, previously considered 'junk' DNA, in the regulation of proteins."
                              http://www.sciencedaily.com/releases...1003142321.htm
                              Junk DNA, Decoded At Last, Reveals Genetic Mutations Contributing To The Development Of Cancer
                              "To understand the role of junk DNA in cancer development, Dr. Emmanouil Dermitzakis, a professor of genetics at University of Geneva, and his colleagues focused their efforts on a study of colorectal cancer. Using genome sequencing technology, the team of geneticists compared healthy tissue and tumor tissue from 103 patients, searching for elements in the vast, non-coding portion of the genome that might impact the development of colorectal cancer. The UNIGE team was able to identify two kinds of non-coding mutations that have an impact on the development of colorectal cancer. First, hereditary mutations, passive in healthy tissue, were found to be active in tumors and seemed to contribute to cancer progression. Second, the researchers also observed how the mutations acquired over time regulated gene expression and affected both the genesis and progression of colorectal tumors."
                              http://www.medicaldaily.com/junk-dna...-cancer-294552
                              Transposable Elements: No More 'Junk DNA'
                              "Since the advent of whole-genome sequencing, transposable elements (TEs), just thought to be 'junk' DNA, have been noticed because of their numerous copies in various eukaryotic genomes. Many studies about TEs have been conducted to discover their functions in their host genomes. Based on the results of those studies, it has been generally accepted that they have a function to cause genomic and genetic variations. However, their infinite functions are not fully elucidated.

                              ...In cases where an inserted TE causes a harmful effect on its host genome, the TE is likely to go to inactivation and fossilization by evolutionary accumulation of mutations and silencing effects...

                              ...DNA methylation is a strict silencing mechanism, and the host genome could use this process to repress the activation of TEs. In general, DNA methylation occurs in CpG dinucleotide. Because Alu and SVA elements have a high degree of CpG dinucleotides, they are vulnerable to methylation. It was observed that TEs regain their activity to mobilize and regulate the expression of host genes when the silencing effect becomes slackened with increasing genomic instability. In addition, the demethylation of TEs is associated with human diseases, commonly in cancer.

                              miRNAs, one of the most active factors regulating gene expression, could be derived from TEs. Fifty-five genes derived from TEs were identified in the human genome, and their characterization showed that TE-derived miRNAs could potentially regulate the complex and dynamics of human genes.
                              http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543922/
                              Cancer regulator microRNA: potential relevance in diagnosis, prognosis and treatment of cancer:
                              "MicroRNAs (miRNAs) are small (typically 22 nucleotides) non-coding, endogenous, single-stranded RNAs. MiRNA genes are evolutionarily conserved and are located within the introns or exons of protein-coding genes, as well as in intergenic areas. Before the discovery of miRNAs, it had been known that a large part of the genome is not translated into proteins. This so called "junk" DNA was thought to be evolution debris with no function. Recently, the explosive research in this area has established miRNAs as powerful regulators of gene expression. While only about 1,424 human miRNA sequences have been identified so far, genomic computational analysis indicates that as many as 50,000 miRNAs may exist in the human genome, and each may have multiple targets based on similar sequences in the 3'-UTR of mRNA. MiRNAs have been implicated in different areas such as the immune response, neural development, DNA repair, apoptosis, oxidative stress response and others and it is impressive the list of diseases which have recently been found to be associated with abnormal miRNA expression.
                              Here, we focus our attention on the importance of cancer regulator miRNAs. They are divided into oncomiRs and anti-oncomiRs that negatively regulate tumor suppressor genes and oncogenes, respectively. Importantly, the association of miRNAs with cancer has prompted additional functional classification of these short RNAs and their potential relevance in cancer diagnosis, prognosis and treatment
                              http://www.ncbi.nlm.nih.gov/pubmed/22204349
                              Pseudogenes: Pseudo-functional or key regulators in health and disease?
                              "Pseudogenes have long been labeled as "junk" DNA, failed copies of genes that arise during the evolution of genomes. However, recent results are challenging this moniker; indeed, some pseudogenes appear to harbor the potential to regulate their protein-coding cousins. Far from being silent relics, many pseudogenes are transcribed into RNA, some exhibiting a tissue-specific pattern of activation. Pseudogene transcripts can be processed into short interfering RNAs that regulate coding genes through the RNAi pathway. In another remarkable discovery, it has been shown that pseudogenes are capable of regulating tumor suppressors and oncogenes by acting as microRNA decoys. The finding that pseudogenes are often deregulated during cancer progression warrants further investigation into the true extent of pseudogene function. In this review, we describe the ways in which pseudogenes exert their effect on coding genes and explore the role of pseudogenes in the increasingly complex web of noncoding RNA that contributes to normal cellular regulation.

                              EVOLUTION AND CONSERVATION OF PSEUDOGENES
                              "Pseudogenes are sometimes considered to represent "neutral sequence," in which mutations that accumulate are neither selected for or against (Li et al. 1981). However, this premise relies on the assumption that pseudogenes are functionally inert. There is recent evidence that pseudogenes are functionally active, and therefore, studying their evolution and conservation could support a functional role and give insight into their potential mechanism of action.

                              ....overexpression of a putative pseudogene transcript (Oct4P1) leads to inhibition of mesenchymal stem cell differentiation while stimulating proliferation. An inverse correlation was observed between BRAF pseudogene transcription and the quantity of BRAF mutations during the progression of papillary thyroid carcinoma (Zou et al. 2009). Forced transcription of the BRAF pseudogene stimulated MAP kinase signaling, transformed NIH3T3 cells in culture, and induced tumors in nude mice (Zou et al. 2009). Fascinatingly, the Xist noncoding RNA, which mediates dosage compensation by coating the inactive X chromosome in mammals and mediating epigenetic repression, may have evolved by pseudogenization of a protein-coding ancestor called Lnx3 (Duret et al. 2006).
                              http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078729/
                              To say that crony capitalism is not true/free market capitalism, is like saying a grand slam is not true baseball, or like saying scoring a touchdown is not true American football ...Stefan Mykhaylo D

                              Comment


                              • #30
                                Originally posted by jordanriver View Post
                                Proposal; defining term
                                How about use only "non-functional" or "functional"
                                (even "pseudogene" can refer to functional according to Nature citation in wiki 's 'pseudogene')
                                This is why I posted links to the "function wars", wherein various authorities struggle with various definitions of "function". These vary from "required for the fitness of the phenotype" (includes perhaps 10% of the human genome) to "does something, even if only transcribed" (ENCODE estimates about 80% of the human genome). The problem is, it's often hard to determine a specific function. Some sequences surely have no function, others are clearly critical, but there are sequences that have been conserved for very long periods but whose function is not known. So "function" here is defined indirectly - IF a given sequence is conserved (or almost exactly conserved, where variations are few and synonymous) for long enough, THEN it's functional even if the function has not been determined.

                                But even so, consider a sequence that functions as a "spacer", doing (apparently) nothing more than using up enough space to prevent frame shift errors between chromosomes during reproduction. This function is important, BUT the spacing sequence is free to mutate quite drastically, so long as it does not change size. So non-conservation isn't a sure indication of non-function either.

                                Another concern here is that evolution tends to be very opportunistic. Let's say a gene breaks, no longer serving the only function it had. Let's say immediately after this, it becomes "junk". BUT before it can be lost, some mutation permits it to be repurposed. Homologies across the biosphere show extensive repurposing, from the examples you give up to the former "ribs" that eventually became parts of the ear, etc. We do the same thing - a broken chair is often used as a doorstop, a clothes hanger, even for firewood. So there might be periods of non-function during a longer process of change in function.
                                Last edited by phank; 08-26-2014, 08:43 AM.

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