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New Science Of Metagenomics to Transform Modern Microbiology?

Posted by ScuttleMonkey on Mon Apr 02, 2007 03:22 PM
from the looking-at-the-small-big-picture dept.
ScienceDaily has a look at the emerging field of metagenomics that watches the DNA of whole communities of microbes to better understand the microbial world. "Metagenomics studies begin by extracting DNA from all the microbes living in a particular environmental sample; there could be thousands or even millions of organisms in one sample. The extracted genetic material consists of millions of random fragments of DNA that can be cloned into a form capable of being maintained in laboratory bacteria. These bacteria are used to create a "library" that includes the genomes of all the microbes found in a habitat, the natural environment of the organisms. Although the genomes are fragmented, new DNA sequencing technology and more powerful computers are allowing scientists to begin making sense of these metagenomic jigsaw puzzles. They can examine gene sequences from thousands of previously unknown microorganisms, or induce the bacteria to express proteins that are screened for capabilities such as vitamin production or antibiotic resistance."
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  • how do you... (Score:3, Insightful)

    by jhfry (829244) on Monday April 02 2007, @03:32PM (#18578747)
    extract dna from millions of microbes?

    I always thought that DNA extraction was a manual process... or at least it required a significant amount of manpower to get.
    • Re:how do you... (Score:4, Informative)

      by Dr. Eggman (932300) on Monday April 02 2007, @03:38PM (#18578839)
      Even if it is manual, there's nothing that says each piece of DNA has to be extracted one at a time. It could be done enmass by taking 'millions of microbes,' shredding the cells and running them through some sort of filter or enzyme that removes the cellular material and leaves the DNA as atleast some fragmented wholes.
      • Re: (Score:3, Informative)

        Even if it is manual, there's nothing that says each piece of DNA has to be extracted one at a time. It could be done enmass by taking 'millions of microbes,' shredding the cells and running them through some sort of filter or enzyme that removes the cellular material and leaves the DNA as atleast some fragmented wholes.

        Which is, as I understand it (my wife does DNA extraction as part of her job) how DNA extraction is done, anyhow, whether its from a single multicellular organism or a mass of (normally, rel

    • That's the point! You scoop up a bit of seawater or goop or whatever, extract DNA from everything in one shot and sequence the whole mess simultaneously. That's the "meta" part.
      • Re: (Score:3, Insightful)

        Ok... I get it now... I just learned more about DNA extraction in the last few minutes as I researched this on my own then I ever thought I would know!

        Gotta love curiosity. We really need an educational system that fosters curiosity and research above all else... it makes learning so much more fun.

        Thanks for the reply!
        • Problem is, the insatiably curious people go into science or engineering or something like that. Teaching gives very few opportunities to satisfy one's curiosity -- at least in a professional capacity. I'm not making any claims about what teachers do in their spare time. And that's certainly not to badmouth teachers either; teachers who love what they do and teach with passion do more good in the world than almost anyone else in the world. But because teaching focuses on what's already known, the best i
          • What I mean, is that I wish we could foster that curosity and make all students interested in discovering and understanding the world around them, the languages we use, and the way our society works and how we can make it better.

            If we could take a kid, from the time that they ask 'why?' about everything, and keep them in that super-curious state all the way through college... we wouldn't need to teach them so much as assist them in teaching themselves. And best of all, they would remember and understand th
    • Re: (Score:3, Informative)

      I am not a biologist, but I was under the impression that current gene sequencing techniques involved taking a rather large sample, mashing it up to break the cell walls and release the DNA molecule from the nucleus, introducing enzymes to further break the strands into smaller, manageable lengths, {magic, wherin those shorter molecules are actually translated to bits on a computer somewhere}, then pattern matching to splice the pieces back together digitally thereafter.

      In theory, this would sequence everyt
    • ...which is why you're still having trouble. The article is in fact about new developments that allow this sort of thing, which as your belief would indicate, has not been possible so far. Check out this paragraph from TFA.

      "Although the genomes are fragmented, new DNA sequencing technology and more powerful computers are allowing scientists to begin making sense of these metagenomic jigsaw puzzles. They can examine gene sequences from thousands of previously unknown microorganisms, or induce the bacteria

      • These kinds of molecular techniques do have an incredible amount of potential, but I am also worried that they could cause us to start neglecting other, vital questions. OK, I've got the genome of these various microbes, fine... but which ones are common in the environment, and which are rare? What do they consume? What consumes them? What proteins do the genes code for? Trying to reduce the complexity of biology down to a genome may cause us to ignore other, important questions.

        It's like trying to unders

        • Yah, the term for this is the "structure-function paradox" and you will see it more and more when you compare disciplines like physics and biology.

          Trying to take a ton of very granular heterogenous data (structure) and trying to figure out the function (how the system "works" or what it "does," or the understanding of the system as a gestalt) gets harder the more data you pick up. This is the problem biologists face and most of the new techniques in bioinformatics are specifically geared to solving it.

          As a
    • Re: (Score:2, Informative)

      Extracting DNA is actually a somewhat trivial process, easily done at home [utah.edu] with common household products [wikipedia.org].

      Its just a matter of breaking down the cell membranes- which are essentially fatty acids with proteins in them, easily dissolved by detergents. Next, separating the DNA from the rest of the cytoplasm, by putting the extract in alcohol.

      A more challenging aspect is preparing the extracted DNA for analysis; you have to clone and amplify the DNA in order to make a DNA library, that becomes more expens
    • You could use one of these [americaninstrument.com] (scroll down), for starters [milk.com].
    • Re: (Score:3, Interesting)

      I always thought that DNA extraction was a manual process... or at least it required a significant amount of manpower to get.
      Nope. That's pretty much been automated in the laboratory, as has much of the analysis. A lot easier than sorting and isolating individual critters, anyway...
    • Re:how do you... (Score:5, Informative)

      by goombah99 (560566) on Monday April 02 2007, @04:01PM (#18579133)
      Meta genomics is usually applied to unculturable communities. As such it can only be done when the source is so abundant that one can get enough DNA to be able to sequence it.



      The best this can do is tell you what genes are present in abundance. Often you may also need primers for that gene so you have to guess a portion of it before you go looking for it. Thus one has some blind spots but these are no worse perhaps than the simple reality that one must always miss some of the low concentration genomes. The presumption is that higher concentration genomes are the most important. That's debatable. If a martian sampled our planet he'd conclude we are irrelevant, and probably that nothing but the top layer of sea water was relevant, given the profile of DNA concentration. Maybe he's right, but I think he'd be missing out on using this to explain a lot of phenomena on earth. How would this explain for example high rise building, deforestation, or changes in the atmosphere, let alone nuclear explosions. For those you might need to sequence us.

      Another problem with this kind of analysis is that while it tells you what is there it does not tell you how the genes interact. For that you need to measure things under varying condittions where relative abundances shift. E.g. finding conditions where nominally the same populations exist--highly coupled envirnonments in equilibrium--where there are different stresses and opportunities. Perhaps the best example of this is depth profiles in sea water. However, obtaining enough degrees of freedom in the experimental conditions, so that one can correlate DNA presence patterns is rough. These self-simmmilar variations can be factored out only under assumptions that need to be justified. Typically Linear factors are assumed and that's almost certainly not true. It certainly would be false in any situation involving either negative feedback or saturation effects. getting enough sample points of entire meta genomes is thus the limit. It's pretty heroic to do even one. And of course one replicate is not enough since one can't distinguish noise from variations one is seeking. So it's all very hard.

      Thus it's sort of a race which will prove more powerful. Reductive decomposition of a population one species at a time or a discovery based meta genomic analysis.

      the simple answer is we need to do both. When it works reduction is far more conclusive about interactions. But there's likely some aspects of community life that dont reside in any one geneome but are traits that float around between different "owners". Likewise, most environments like ground soils have proven to be unculturable so one is sort of stuck with metagenomics or nothing.

      • Meta genomics is usually applied to unculturable communities. As such it can only be done when the source is so abundant that one can get enough DNA to be able to sequence it.

        Abundance of material doesn't pose a problem. Soil samples are so abundant in diverse microorganisms that its actually a problem later on. For water sampling it is quite straight-forward to use tangential flow filters to collect sufficient biomass by simply processing the appropriate volume of water.

        Of the shotgun sequencing type,

      • How would this explain for example high rise building, deforestation, or changes in the atmosphere, let alone nuclear explosions. For those you might need to sequence us.


        You cracked me up.
    • How do you extract dna from millions of microbes?

      You use metagnomes. They're the same gnomes who carry out step 2. If they can figure out how to extract profit from underpants, they can figure out how to extract DNA from millions of microbes.
      • Hopefully they won't cross-class and figure out how to extract profit from microbes. Or worse, how to extract DNA from millions of underpants...
    • how do you extract dna from millions of microbes?

      Extracting DNA is very easy:
      • Smash up a tissue sample (or, in this case, whole organisms)
      • Add a lysis buffer (soap + salt)
      • Add ethanol to precipitate the DNA

      The next step, cloning, is also easy to automate:

      • Add a restriction enzyme (such as EcoR1) to break up the DNA into smaller pieces
      • You now have random DNA fragments; put them into a vector (plasmid, a circular chromosome)
      • Trick some nice friendly bacteria (like E. Coli) into taking the plasmids int
    • I always thought that DNA extraction was a manual process...

      You'd be surprised.
      Modern PCR kits have become so much robust that you can put almost anything at them, and they still manage to duplicate the exact piece of genes that you need, without much artifacts.

      At the last lab where I worked we use to take bacterial colonies and shake them with microbeads and... and thats it.

      We developed a fast, high throughput and dead-cheap methods for genotyping (ie.: puting into sub-families according to gene properties

  • Sounds like this would be just the sort of thing to test out potential DNA snippits before we insert them into our GM foods. I'm all for more GM foods, but I wouldn't say no to a better method of testing. If we could raise large colonies of bacteria with the candidate DNA snippit and 'control' groups without the snippits, we could then use Metagenomics to track protien expressions in the GM colonies and watch for unwanted expressions as well by comparing them with the data gathered from the control colonies
    • Not even close...first of all, such a system wouldn't tell you anything about the interaction of the newly transgenic protein with the host species' proteome (i.e., the normal protein background of say, corn); it would only tell you what the protein does by itself. And if you don't know that already, why would you be trying to insert it into food?

      Nor is metagenomics all that interesting in pure cultures, where you've got billions of bugs with almost identical genomes. It will be much more useful in an extre
  • It would be nice to see if they can do this within a small, confined area, like onboard a small underwater craft to study microorganisms that would otherwise die if removed from the depth. There's bound to be a lot of weird stuff down there that can't currently be studied.
    • In order to sequence DNA you need to completely destroy the cell that houses the DNA (sort of like shucking corn)... so you are going to have to kill whatever you are sequencing (or some of the cells at least... and they are talking about organisms with small cell counts here).
    • I believe this is already being done. I've talked to a VP in a company in this field and he was telling me how they got organisms from extreme environments: undersea volcanic vents, etc.
  • New paradigm (Score:3, Interesting)

    by drooling-dog (189103) on Monday April 02 2007, @03:50PM (#18578975)
    This is really a new paradigm for microbial ecology. Instead of worrying about how thousands of different species (most of them unknown) are interacting with each other, you can now think about what genomic and proteomic resources are present in a habitat. Think of the organisms themselves as just the bags that contain what you're really interested in looking at, and suddenly a lot of insights and high-throughput techniques open up to you.
    • This is a bit like the communist theory that people would share their different abilities freely. Ignoring the aspect that by not sharing freely but only strategically one can achieve both success and simultaneously a more productive community (in terms of resource exploitation) would make understanding capitalism difficult when put under the communist martian's microscope. Thus if this analogy holds determining which "bags" hold which traits may turn out to be more important in determining behavior than
      • Well, I just had 2 pints of beer so I'm not quite sure I understand where the communist ideology fits in, but yes, there is value in understanding how all of the inputs and outputs of a system (social or otherwise) balance out, and now these are can be analyzed very cheaply and easily. Are there feedback loops, synergies, competitive relationships and the like? Sure, and they're important, but this is just another perspective on things that adds to our understanding. It would be tragic if it lead to a deval
  • There was a game called Spore being developed, you would took life from microbial stages of evolution to an interstellar civilization stage. what happened to it i wonder.
  • Source (Score:4, Interesting)

    by Red Flayer (890720) on Monday April 02 2007, @03:59PM (#18579111) Journal
    The article was taken from a National Academies press release [nationalacademies.org]. Here's the full report [nap.edu], parts of which (maybe the whole thing? I didn't check) can be previewed as a pdf if you don't want to purchase the book.

    Oh, and here's a brief (4-page summary) of the report [nas.edu].

    Woulda been nice to have the source info in the summary...
  • US audience:

    Don't tell any Republicans about this.

    The prez is already concerned about the possibility, and I quote from a speech: "human-animal hybrids".

  • Related Resource (Score:2, Interesting)

    by Anonymous Coward
    The Craig Venter Institute's Global Ocean Sampling Expedition has been collecting Metagenomic samples for the past couple of years. Among other things the expedition has doubled the number of putative proteins. An excellent video from the expedition is available at http://plos.cnpg.com/lsca/webinar/venter/20070306/ index.html [cnpg.com] and a set of recently published papers from the expedition are available for free at http://collections.plos.org/plosbiology/gos-2007.p hp [plos.org]

    A website hosting the data from the expediti
  • Since it handles microbes and DNA, it's mildly related:

    You know, pondering about evolution, there is only one thing I have difficulty understanding with evolutionism (which I am a strong proponent of). I don't know if you're a biologist or not, but if someone could give me a good explanation I would be glad.

    In the case of social groups of insects, like bees and ants, you have different classes/groups of individual insects within one hive, some of which are highly specialised. I can't quite understand how th
    • Re: (Score:2, Informative)

      I think you understand the steps in reverse order.

      1. a mutation happen randomly in sperm or egg.
      2. a new queen is born from this mutated reproductive cell.
      3. mutation is positive (e.g. the slave from this queen are more efficient)
      4. the queen give birth to more new queen than one with less efficient slaves

      Let's look at it in another way.
      Infertile workers are like our cells. You can have one white cells which is resistant to HIV, but this mutation won't be passed to your offspring. But maybe one of your sper
      • No, I don't understand it in reverse order. Sigh. This is why I'm never keen to ask anything on slashdot for specific knowledge; one is always treated like some retard, even by people with the best of intentions. I mean, I know that a mutation in a white cell will not pass on to any offspring; that was what I said with my example of organs (the heart). And I know evolution is a very slow process.

        Anyway, you are just trying to be helpful, I suppose. People seem to be a bit on the wrong track whith what I'm a
    • In the case of social groups of insects, like bees and ants, you have different classes/groups of individual insects within one hive, some of which are highly specialised. I can't quite understand how that works, using darwinistic evolution. When one follows the theory of evolutionism with, say, mammals, it makes sense: a genetic change in sperm or egg can lead to an indivdual who is less or more adapted to their environment, and this indivdual passes those traits to his/her offspring.

      But, in the case of so

      • While I admit I didn't read it yet, I'm aware of it's content, and I know there is a lot of critique on it as well. I had a sample of that criticism in the book I'm reading now, which is 'man, beast and zombie'...something I would recommend reading to everyone as well.

        Anyway, people seem to be a bit on the wrong track whith what I'm asking (maybe I explained it wrongly). I'm quite aware of how the way evolution works, and the importance of genes, but I would like to know the specifics how a mutation is tran
        • I'm quite aware of how the way evolution works, and the importance of genes, but I would like to know the specifics how a mutation is transferred by a queen, which is only usuable to worker-ants...

          A queen doesn't do anything, essentially, but lie around and produce offspring. Whether any of the few (proportionately) of those offspring which are fertile have reproductive opportunities depends on the success of the colony, which depends on how effective the workers (etc.) are. Ergo, a queen that produces more

        • all the mutations are in the genes of the queen, but none of it comes to expression in the phenology of the queen

          This is more or less correct. I think what most of the folks here are getting hung up on is some slight miss conceptions and a bit of confusion over your slightly odd use of terminology.

          Okay, A summary of a few points to (hopefully) clear up some of this confusion:

          It is important to distinguish between somatic cell mutations and germ line mutations. Based on what you've said already, it se

    • only one thing I have difficulty understanding with evolutionism (which I am a strong proponent of)

      You're lying. Seriously. Only creationists use phrases like "evolutionism" and "darwinistic evolution."
      • "Only creationists use phrases like "evolutionism" and "darwinistic evolution."

        Your lying. Seriously. Kenan Malik uses 'evolutionism', and one can hardly claim he's a creationist. As an atheist, it would be rather difficult for me to believe in ID.

        Being not native english, I'm not sure what you're getting at; are you implying the terminology is wrong? When I check in an online english dictionary, I see:

        evolutionism (v'-l'sh-nz'm, 'v-) Pronunciation Key
        n.
        1)A theory of biological evolution, especially
        • The original poster has a point: in English, creationists use the term "evolutionism" far more than non-creationists. Non-creationists just say "evolution". Some speculate that the creationist terminology originated from an attempt to make evolution seem less scientific, since the "-ism" suffix is often used to refer to ideologies or belief systems (such as "creationism"!). This is especially apparent when creationists refer to evolutionary biologists as "Darwinists". Try here [pandasthumb.org] (halfway down) and here [cotch.net] a
      • Well, simple enough...ermm...that's to say...can you elaborate, using an actual example of how that would actually happen?

        For instance, like me example:

        "Say the ancestors of the current ants were more simple, less specialised. At a certain moment, in the DNA of a queen-egg, there occurs a mutation; this mutuation turns out to be beneficial - say, the worker-ant develops an enzym which is far more efficient in providing digestable nutrients from raw food, for instance. Now, that ant lives its life, then dies
        • Re: (Score:3, Informative)

          You see, that's where I don't get it: worker ants can be higly specialised, for instance, I've seen ants in the form of (relative) giant sacs which only were useful for storing some sweet excrement other ants gave them. Clearly, a queen having that mutation would die.

          The problem with this is that it ignores that not all genes an organism has are necessarily expressed and that, particularly, the expression of genes may be triggered (or suppressed) by environmental conditions or by the presence or absence of

  • Sad tendency (Score:3, Interesting)

    by mapkinase (958129) on Tuesday April 03 2007, @04:05AM (#18584787) Homepage Journal
    The advent of metagenomics is accentuating a sad trend in science: less lab work, more computers. Do not get me wrong, I feed my kids from the computer desk and I have never touched an "Eppendorf" or "Pipetteman" (not sure about spelling). In the race for grants we are chasing aggrandisement of the projects we are applying to NSF and DOE. More computers, more modeling instead of experimenting.

    I have been reading scientific literature for almost 25 years and the tendency is clear: the results of "computer experemints" (read, modeling) are trusted more and more without any experimental verification. The procentage of sequences in GenBank and Refseq which function is determined only by homology to existing proteins grows. That means we are guessing the function of new proteins by comparing them to the proteins which function we also guessed by comparing to earlier proteins, etc...

    Number of protein folds is limited: 700, 1000, 30000, does not matter: it is limited, but it does not mean the functions are limited in the same way. How on earth are we going to find out the function of completely new protein that have not enough similarity to anything in the database? We cannot do it on computers.

    And obviously we do not have resources to research experimentally 1.5M genes in Refseq. So instead of blindly pumping more and more raw data into our RAID arrays, we need to be more focused on researching the genes, proteins, pathways that have a direct impact on medicine. You know, "stuff that matters".
      • Are you listening? I am telling you that databases you are using get worse and worse, because functional annotation average protein is further and further from experiment and you are telling me that you enjoy using them. Crap in, crap out.
          • YOu do not get it. It is not about the use of computations. It is about deterioriating quality of the computational data that people keep relying on.
    • I'm not sure whether the above post should be marked "astroturfing" but it sure reads a little too positive.

      454's sequencing technology is a welcomed addition to existing technologies, but don't believe the hype, particularly when the person talking has stock options.

      The analysis of genomic sequencing data (metagenomics or otherwise) is highly benefited by large contiguous pieces or ideally whole contiguous genomes. Related to this and more fundemental is the fact that the shorter the pieces of DNA spat