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Human Genome More Like a Functional Network

bshell writes "An article in science blog says we may have to rethink how genes work. So called "junk DNA" actually appears to be functional. What's more it works in a mysterious way involving multiple overlaps that seems to be connected in some sort of network." From the article: "The ENCODE consortium's major findings include the discovery that the majority of DNA in the human genome is transcribed into functional molecules, called RNA, and that these transcripts extensively overlap one another. This broad pattern of transcription challenges the long-standing view that the human genome consists of a relatively small set of discrete genes, along with a vast amount of so-called junk DNA that is not biologically active. The new data indicates the genome contains very little unused sequences and, in fact, is a complex, interwoven network. In this network, genes are just one of many types of DNA sequences that have a functional impact. "Our perspective of transcription and genes may have to evolve," the researchers state in their Nature paper, noting the network model of the genome "poses some interesting mechanistic questions" that have yet to be answered."

18 of 304 comments (clear)

  1. Of course its not junk by thogard · · Score: 5, Interesting

    Its what we in the programming field would call the Data Segment.

    1. Re:Of course its not junk by Profane+MuthaFucka · · Score: 5, Funny

      If an analogy were something standing up, it could fall down. But if it's a car then the analogy would drive away.

      --
      Fascism trolls keeping me up every night. When I starts a preachin', he HITS ME WITH HIS REICH!
    2. Re:Of course its not junk by Founder+of+PostGenet · · Score: 5, Informative

      The genome is fractal - governing fractal growth of organelles, organs and organisms. Even from a single fractal template (e.g. the algorithm of z=z^2+C) an enormously "complex" pattern, full of self-similar repetitions will develop. The "gene"-parts of the genome determine "fractal templates" of proteins, while the "PostGene"-sequences supply the auxiliary information necessary for iterative hierarchical development (architecture of complex protein structures). This concept/utility (FractoGene) triggered 300+ entries in slashdot in 2002 when an algorithmic approach first challenged the "gene/junk" dogma. The saga (including slashdot reference) is recorded at http://www.junkdna.com/ (as well as on http://www.fractogene.com/ ) Of course it is not junk... "junkDNA" is not a scientific term any more - but an important nickname for "the biggest mistake in the history of molecular biology". pellionisz_at_junkdna.com

    3. Re:Of course its not junk by TekPolitik · · Score: 4, Insightful

      Its what we in the programming field would call the Data Segment.

      Overlapping, independent sequences? It's quite obviously spaghetti code.

    4. Re:Of course its not junk by Grail · · Score: 4, Interesting

      In laymans terms, the "Junk DNA" provides the bootstrap routine and program code of an life form building nano-machine. The "Gene DNA" provides the instructions to the life-form-building-machine on how to make this life form a "human" or "fly" or "bacteria".

      Papers such as A minimal gene set for cellular life derived by comparison of complete bacterial genomes provide some first steps into understanding how all this DNA works together.

      And to the grandparent post - I would argue that the "junk DNA" is not the data segment. For decades we've been thinking of the "Gene DNA" as the program when it is in fact the input data, while the "Junk DNA" is the boot loader, operating system and interpreter. But the machine doesn't build stuff and then move on (like a human-built factory) - it replicates itself, subtly altering the replicants to become more specialised along a growth path that will make one new machine produce stuff that will eventually become a femur, while the other new machine starts building stuff that will eventually become a gluteus maximus.

      I've heard of a project where a company set out to create a synthetic bacteria based on the minimal possible DNA, which they could then patent, and use as a base for testing genome manipulation or gene therapy or some such nonsense. Not sure if that's fact or fiction though.

    5. Re:Of course its not junk by cdn2k1 · · Score: 4, Funny

      It's like the Internet. At a glance it looks like you've made an insightful comment. But if you study it too closely you realize you've just made another redundant posting.

    6. Re:Of course its not junk by MikShapi · · Score: 4, Insightful

      Not quite. Your analogy appears somewhat broken.

      Here's the question - is non-gene DNA /machinery/ or /DATA/?

      If it's the latter, junk DNA would be conceptually closer to filesystem metadata (and maybe even "free diskspace" in as far as introns etc. go) than the OS.
      I fail to see how it bootstraps anything. A DNA molecule does not to my best knowledge start proliferating on its own when put on agar. Cellular facilities are required. True, you build said cell facilities from data stored in genes, but still I can't find any underlying principle shared by the bootloader, OS or whatever interpreter on my computer and my non-gene-coding DNA.

      FWIW, I'm a coder, a unix sysadmin and a (somewhat late-aged) biochem undergrad student, so feel free to dive as deep as you like into a technical comparison. I've been playing with comparison models of my own for a while (all of which have the annoying habit of breaking at one point or another) and am intrigued to hear more ideas on this.

      --
      -
    7. Re:Of course its not junk by ikkonoishi · · Score: 4, Funny

      A metacar?

      Or would that be a car that would only allow other cars to ride in it?

  2. My hairbrained idea... by Panaflex · · Score: 4, Interesting

    It's somewhat funny - I remember having this exact discussion with my genetics professor. I was a chem major who is now a developer.

    It seems to me that DNA/RNA is "machine code" and data which runs on the laws of nature. It's a layer removed from silicon design, more akin to a self-modifying FPGA.

    In other words we're so far only looked at the boot code and associated data. The "program" is what we were calling junk.

    And it makes sense - if you think of the program as a massive recursion network which builds common parts (stem cells) and then organizes and specializes.

    I know that's a simple bastardization ... but perhaps I've just looked at too much dissassembler. I will feel a little vinticated if this is proven.

    --
    I said no... but I missed and it came out yes.
  3. Re:error correction by crashfrog · · Score: 4, Informative

    I don't think evolution would be very kind to unneeded material.

    There's really almost no selection pressure against extra DNA sequences, particularly ones with no associated promoter. One of the proofs of this is the fact that the human genome is comprised more of endogenous retroviruses than actual functional sequences.

    --
    I never have frustrations, the reason is, to wit:
    If at first I don't succeed, I quit!
  4. Its just code that's there for debugging purposes by timothydsears · · Score: 4, Funny

    These scientists have probably been looking at cells running in the debugger...

  5. sneaky by Takichi · · Score: 4, Funny

    Our perspective of transcription and genes may have to evolve well played ... well ... played.
  6. Junk DNA by narced · · Score: 4, Funny

    I walk down the street and see 100s of people who appear to be predominantly junk DNA.

  7. This is hardly 'news'.. by comm2k · · Score: 4, Interesting

    Why it was called junk before you'd ask? Because our definition of what is useful wasnt all that accurate.. just looking at so called open reading frames and declaring everything else to be junk does not work. There is also the problem with insertions in a gene sequence that are either not or alternatively used. There are plenty of sequences that are never translated (no proteins are made of it) BUT without them we would be missing a big chunk of regulators etc. 'Recent' findings like ribozymes, IRES elemtens, attenuation elements etc. are all not translated into a protein yet serve a very specific function. Some of this 'junk' also serves as a insulator / separator between various sequences. We may never be able to map every nucleotide to some function but declaring it junk from the get go was just looking to be proven wrong. Just look up NCBI and look for some good reviews on this topic ;)

  8. Re:junk genes was a junk idea by Daniel+Dvorkin · · Score: 5, Interesting

    Whenever I read something like this, I get a reminder how poor is biologists' comprehension of Computer Science, Information Theory, and languages.

    Whenever I read a post like this, I get a reminder how poor is most techies' comprehension of biology, and more specifically, what biologists do.

    Third, why this obsession with zeroing in on a magic gene that causes X? Do they think the language of DNA is context free? Defects could indeed be expected to have no context, but for the rest-- which genes determine a person's blood type? Eye color? Skin color? Going about that task by trying to find the magic gene for something like that is like a person who never learned to read trying to figure out the plot of a book by trying to recognize patterns of letters.

    Okay, why do we care? Because finding the genes (note my use of the plural there) that influence certain traits is the first step toward understanding the overall processes that create them. Obviously this is most critical in the area of genetic disease, although it's interesting for everything else too. We've known for decades that most traits, including diseases, aren't controlled by a single "magic gene." What statistical geneticists try to do is find locations on the genome which have a strong relationship to the trait of interest. And we know perfectly well that there will be a whole bunch of these locations for most traits, and that some of them may represent genes and some may represent something else. The purpose is basically to give the wet-lab biologists something to zero in on.

    Second, two of the examples you chose -- blood type and eye color -- are really terrible ones for your argument, because genetically speaking they're very simple traits (two or three loci each, IIRC) and, at least in the case of blood type, we know exactly where they are in the genome. Eye color I'm not sure about, and skin color is a little more complicated, but not a whole lot more so.

    Please do not confuse the pop-sci "scientists seek gene for X" writeups with what really goes on in the world of genetic research. It has exactly as much to do with real science as TV portrayals of hackers have to do with real computing.

    --
    The correlation between ignorance of statistics and using "correlation is not causation" as an argument is close to 1.
  9. Re:error correction by cnettel · · Score: 4, Insightful
    Genome space is damn cheap, just like disk space. The added tax on each cell to carry bloat is minimal. No matter how much is transcripted, we can analyze the sequences that we do see in the "junk". They are often very repetitive, with some sequences clearly deriving from viruses that integrate into the genome. The added selectional advantage of having the same (possibly now suppressed, but originally pathological) sequence, over and over, should be quite small, and the pattern and frequency of changes seems to indicate that most of these regions do not undergo any directed selection, i.e. mutations that do appear are kept at random, indicating "no value".

    We have this huge disk, and most of it is malware or free space. The results in RTFA are interesting, but the general idea that we can measure the frequency of changes and statistically determine whether evolution is working on a specific sequence, should still be sound, so if they are indeed used, it is probably in a far less sequence-sensitive context (sometimes overall folds, sometimes just stochastic effects from the whole pool of junk transcripts affecting the balance in the nucleus).

  10. Re:error correction by dch24 · · Score: 4, Interesting

    crashfrog, you may have to correct me, but here's a start...

    There's really almost no selection pressure against extra DNA sequences,
    This refers to the process in evolution where an organism fails to reproduce due to having a disadvantage that the other critters in the species don't have. So if a pig that has useless DNA sequences tacked on in its genome has a statistically lower chance of having piglets, there's pressure against those useless DNA sequences.

    crashfrog is saying that for a reason he explains (below) extra DNA isn't going to have any effect on the organism's chances of reproducing.

    particularly ones with no associated promoter.
    A promoter is a marker in the DNA strand. The protein "machine" (a transcription factor) that gets the "data" off the DNA and into the cell's outside chemistry has a "socket" that matches the "plug" formed by the specific pairs of the "promoter" marker. It's like the transcription factor searches for #! /bin/perl and that's how it knows to start copying off DNA code. (While on the subject, just because it has #! /bin/perl doesn't mean it will get executed, and even after it's been executed it might get a SIGKILL.) Promoters are not just found in DNA, but read on wikipedia for more on that.

    One of the proofs of this is the fact that the human genome is comprised more of endogenous retroviruses than actual functional sequences.
    I'm not sure if I can do this last sentence piece by piece, so here goes...

    An endogeneous retrovirus is a kind of virus that infects DNA. So when the cell splits, the virus gets copied along with it. For instance, some scientists think Multiple Sclerosis is one of these retroviruses that has infected our DNA. So when we look at the entire human genome, all the pairs in the whole DNA sequence, and we look at where all the promoters are, it seems (according to current theory -- we may learn more about this!) at a first glance there are some pretty long stretches with no promoters. That is to say, they are either empty sectors on the disk, or some of them look like retrovirus DNA code.

    How'd I do at explaining that? Like I said, crashfrog should probably amend my explanation...

  11. Re:Messy Speghetti Help by Savage-Rabbit · · Score: 4, Interesting

    They need to hire some Perl and 60's-style-COBOL programmers who know how to read tangled code ;-) My experience with Perl developers is that writing tangled code isn't a problem for them. It's reading, even their own, tangled code that they find difficult. I sat down with a Perl guru where I worked some years ago trying to debug a particularly nasty piece of Perl code. The whole time he kept going on about "Who writes code like this!?!" until we looked it up in the CVS repository and it turned out it was he himself who wrote that particular block a few years earlier. Syntactic flexibility is nice but it has a downside.
    --
    Only to idiots, are orders laws.
    -- Henning von Tresckow