National Geographic

Yet-Another-Genome Syndrome

There’s a certain kind of headline I have become sick of: “Scientists Have Sequenced the Genome of Species X!”

haemophilus genome 440Fifteen years ago, things were different. In 1995, scientists published the first complete genome of a free-living organisms ever–that of a nasty germ called Haemophilus influenzae. Bear in mind, this was in the dark ages of the twentieth century, when a scientist might spend a decade trying to decipher the sequence of a single gene.

And then, with a giant thwomp, a team of scientists dropped not just one gene, but 1740 genes, spelled out across 1.8 million base pairs of DNA. At the core of the paper was an image of the entire genome, a kaleidoscopic wheel marking all the genes that it takes to be H. influenzae. It had a hypnotizing effect, like a genomic mandala. Looking at it, you knew that biology would never be the same.

Looking over that paper today, I’m struck by what a catalog it is. The authors listed every gene and sorted them by their likely function. They didn’t find a lot of big surprises about H. influenzae itself. It had genes for metabolism, they reported, and genes for attaching to host cells, and for sensing the environment. But scientists already knew that. What was remarkable was the simple fact that scientists could now sequence so much DNA in so little time.

Then came more microbes. Then, ten years ago this coming June, came a rough draft of the human genome. Then finished drafts of other animals: chickens, mice, flies, worms. Flowers, truffles, and malaria-causing parasites. They came faster and faster, cheaper and cheaper. The acceleration now means that the simple accomplishment of sequencing a genome is no longer news.

torrent220On Wednesday I caught a talk at Yale by Jonathan Rothberg, a scientist who invented “next-generation sequencing” in 2005. By sequencing vast numbers of DNA fragments at once, the new technology made it possible to get a genome’s sequence far faster than earlier methods. Rothberg’s company, 454, got bought up by Roche, leaving him without a lot to do. So he came up with a new machine: a genome sequencer about the size of a desktop printer that can knock out complete genomes with high accuracy in a matter of hours. Rothberg has been unveiling details of the machine over the past few weeks. To convince his audience that the machine actually works, he flashed another mandala wheel–the 4.7 million base pairs of E. coli.

I recalled when the first E. coli genome was published in 1997. It was the result of years of work by 17 co-authors, an event celebrated in newspapers. Now Rothberg just threw up a quick slide of the germ’s genome just to show what he could do in a matter of hours. And I have to say that the sight of yet another circular map of a genome, on its own, no longer gave me a thrill. It’s a bit like someone waving you over to a telescope and saying, “Look! I found a star!”

What remains truly exciting is the kind of research starts after the genomes are sequenced: discovering what genes do, mapping out the networks in which genes cooperate, and reconstructing the deep history of life. Thanks to the hundreds of genomes of microbes scientists can now compare, for example, they can see how the history of life is, in some ways, more like a web than a tree. Insights like these are newsworthy. The sequencing of those genomes, on its own, is not.

And yet my email inbox still gets overwhelmed with press releases about the next new genome sequence. The press releases typically read like this:

“Scientists have sequenced the genome of species X. Their research, published today in the Journal of Terribly Important Studies, will lead to new insights about this important species. Maybe it will even cure cancer or eliminate world hunger!”

And then those press releases give rise to news articles. Here are dozens of pieces that came out over the past couple days, describing the freshly-sequenced genome of the zebra finch. What did the scientists actually learn about zebra finches through this exercise? The articles typically referred to 800 genes involved in the birds learning how to sing. Of course, nobody seriously would expect them to use just one or two genes for something so complex, so this was no big surprise. The articles also mentioned that a lot of the genes were similar to human language genes. This is not really news, either. For the most part, the articles look to the future–to experiments that scientists will be able to do on zebra finches, in the hopes of learning about human speech. But that’s not news of an achievement–that’s a promise.

Perhaps press release writers and journalists are still operating on the assumption that any new genome is news. But that assumption has been wrong for years now. Let’s wait to see what scientists actually discover in those marvelous mandalas.

[Update: Thanks to Jonathan Eisen for coining the easy-t0-remember acronym for my current disorder: YAGS. That goes into my personal lexicon right away.]

Add Yours.

  1. Jonathan Eisen
    April 2, 2010

    You have a mini typo – you say Rothwell not Rothberg in the middle …

    [CZ: Fixed. Thanks]

  2. Darren Garrison
    April 3, 2010

    Okay, is that an iPod dock built into the portable gene sequencer?

    http://www.iontorrent.com/ion-personal-genome-machine-sequencer/

  3. Bob O’H
    April 3, 2010

    Oh, you just wait for the mildew genome sequence to be published. Then/i> you’ll be excited.

  4. David
    April 3, 2010

    It would seem that each new genome is not published in The Journal of Terribly Important Studies but in Science or Nature. It is not clear to me why these papers qualify as the type of important new breakthrough that is expected of research in other disciplines for consideration by these journals. Also, I would quibble that the history of prokaryotic life (i.e., Archaea and Eubacteria) may be web like, but that is not as much the case for Eukarya.

  5. Jean Lynn
    April 3, 2010

    Gosh, I’m sorry you’re annoyed when the mainstream media report human-genome results that bore you. And, yes, the hyperbolic interpretations are troubling. And, wow, how cool is the concept that, as you say, “the history of life is, in some ways, more like a web than a tree.”

    How well have I succeeded in presenting myself as a gullible science-illiterate member of the great unwashed?

    One can be both a geek and a human being.

  6. Trevor Marshall
    April 3, 2010

    The fundamental mistake with trying to find association between the human genome and disease, at least until we actually pin down the human genome, and narrow down the current 3 million SNPs (it was actually 20 million at the last conference I attended) to a comprehensible figure, is that human geneticists have not yet come to grips with the fact that the human DNA/RNA fragments they are sequencing are likely contaminated by RNA/DNA from species from the Human Microbiome. I have been trying to promote the concept that the interplay between the human genome and the human metagenome, which we have shown leads to chronic disease, is imponderably huge in scale. Sadly, I find few in Clinical Medicine who are even capable of getting their minds around the word “imponderable,” and even fewer who are prepared to let go of their simplistic concepts describing the way way Medicine thinks human and pathogenic genomes interact. We have an interesting decade ahead of us, as well as behind us…

  7. Damian McColl
    April 3, 2010

    Um excuse me but every genome is exciting and has the potential to reveal novel insights about life. That you find this incredible advancement of genomic technology and the riches of biological information that it brings boring says more about you. Perhaps you have a gene for “limited amazement capacity”. These studies have the power to back up your book “Evolution”.seems to me you might find a deeper and more positive message in this explosion of information.

    [CZ: It is indeed amazing that scientists can now sequence entire genomes so quickly and inexpensively. But the sequencing of any one of those thousands of genomes is not cause for a lengthy article in a newspaper. The insights gained from studying that genome may (or may not) be a cause for one.]

  8. amba (Annie Gottlieb)
    April 4, 2010

    I think it’s really “Yawn . . . Another Genome” Syndrome.

  9. Steve G
    April 5, 2010

    Geneomes are exciting, but with a few exceptions, a 3 page paper describing the GC content, number of genes, and the number of transposable elements is not worth publication in a major journal. It’s also EXTREMELY disappointing to see a genome paper in a big journal, and the authors fail to do their due diligence and make the data available or put it in some form that is useful (i.e. an Ensembl genome browser). Merely reporting on the acquisition of the genome sequence and dumping the supercontig sequences into GenBank is not important without some resources and analysis to back it up.

  10. Matt Mealiffe, MD
    April 5, 2010

    Carl -
    I agree. Although some of the stuff at the bleeding edge of the technology development can be very interesting, the actual sequencing of a genome has become much less interesting (particularly for me when it is non-human). It is what comes after that is so much more fun, interesting, and creative.

    It’s also interesting that when everyone talks about the rapidly falling costs of sequencing, they often do not factor in costs for the downstream analysis and sifting through the data. This, of course, is necessary to maximize the value of the investment one has made in sequencing in the first place.

    Matt Mealiffe

  11. Mike Spear
    April 6, 2010

    You are bang on by noting that what comes after the sequencing is of major importance and I think that is also where the research journals, popular science publications, and general media start to move in different directions. Research papers get published to check off that part of the grant application (apart from the many legit reasons to do it as well), general science publications tweak it to make it understandable to more of the interested public, and the general media finds a way to give it a one-off treatment.
    The follow-up in the general media to that “what happens next” event is generally not as easy to understand, not quite as easy to write headlines for, and is often years after the initial announcement. That leaves the public and the politicians who fund much of this research wondering what all the fuss is over genomics because they see a big story followed by deafening silence.
    Could we soon find ourselves in a similar situation to manned space flight where it became a bit ho-hum, not enough “what do we do with it now” buzz generated, until finally funding started to disappear ?

    Mike

  12. David Pollock
    April 6, 2010

    I can’t help wanting to tweak my old graduate school friend Jon Eisen a bit on this one. I can understand why he might be yawning about more bacterial (or achaeal) genomes, but given that he is still publishing bacterial genomes one at a time in PLoS ONE (1,2,3), and there is almost 300-1000 times as much information in a vertebrate genome, it still seems quite appropriate to publish a vertebrate genome in Nature. Further, since Nature’s impact factor is around 30, it seems that Eisen is perhaps expecting the upcoming (peer-edited and open source) PLoS ONE impact factor to be around 0.1, an abysmally low number. On the other hand, the going ratio of bacterial genomes to vertebrate genomes to get into Nature appears to be 56:1 (4), so Eisen is going to have to start producing a lot more bacteria for next time if the vertebrate papers are going to drop from Nature down to the peer-edited journals.

    1) The complete genome sequence of Haloferax volcanii DS2, a model archaeon.
    Hartman AL, Norais C, Badger JH, Delmas S, Haldenby S, Madupu R, Robinson J, Khouri H, Ren Q, Lowe TM, Maupin-Furlow J, Pohlschroder M, Daniels C, Pfeiffer F, Allers T, Eisen JA.
    PLoS One. 2010 Mar 19;5(3):e9605.

    2) The complete genome of Teredinibacter turnerae T7901: an intracellular endosymbiont of marine wood-boring bivalves (shipworms).
    Yang JC, Madupu R, Durkin AS, Ekborg NA, Pedamallu CS, Hostetler JB, Radune D, Toms BS, Henrissat B, Coutinho PM, Schwarz S, Field L, Trindade-Silva AE, Soares CA, Elshahawi S, Hanora A, Schmidt EW, Haygood MG, Posfai J, Benner J, Madinger C, Nove J, Anton B, Chaudhary K, Foster J, Holman A, Kumar S, Lessard PA, Luyten YA, Slatko B, Wood N, Wu B, Teplitski M, Mougous JD, Ward N, Eisen JA, Badger JH, Distel DL.
    PLoS One. 2009 Jul 1;4(7):e6085.

    3) Complete genome sequence of the aerobic CO-oxidizing thermophile Thermomicrobium roseum.
    Wu D, Raymond J, Wu M, Chatterji S, Ren Q, Graham JE, Bryant DA, Robb F, Colman A, Tallon LJ, Badger JH, Madupu R, Ward NL, Eisen JA.
    PLoS One. 2009;4(1):e4207. Epub 2009 Jan 16.

    4) A phylogeny-driven genomic encyclopaedia of Bacteria and Archaea.
    Wu D, Hugenholtz P, Mavromatis K, Pukall R, Dalin E, Ivanova NN, Kunin V, Goodwin L, Wu M, Tindall BJ, Hooper SD, Pati A, Lykidis A, Spring S, Anderson IJ, D’haeseleer P, Zemla A, Singer M, Lapidus A, Nolan M, Copeland A, Han C, Chen F, Cheng JF, Lucas S, Kerfeld C, Lang E, Gronow S, Chain P, Bruce D, Rubin EM, Kyrpides NC, Klenk HP, Eisen JA.
    Nature. 2009 Dec 24;462(7276):1056-60.

  13. Jonathan Eisen
    April 6, 2010

    Hey I never said I didn’t like the finch genome paper. I simply was quoting Mr. Carl Zimmer and helping him out with the YAGS acronym.

  14. Jonathan Eisen
    April 6, 2010

    But now that my old friend Dr. David Pollock has entered the fray I guess I should comment a bit more. 1) The fact that microbial genomics is light years ahead of animal genomics is the reason why it takes more sequencing to get a microbial genome paper published than a animal genome paper 2) Note – Pollock did not mention that paper #4, which has 56 genomes, is by, well, me. 3) Papers should be judged not by the journal in which they are published but by the content therein. If Dr. Pollock wants to not bother to read papers, and to judge them by what journal they are published in, so be it. I prefer to read papers, and judge them by what they find and report.

  15. miko
    April 6, 2010

    Nature publishes animal genomes because they are citations machines, not because they are interesting science in themselves.

  16. David Pollock
    April 6, 2010

    I won’t extend the discussion of microbes versus animals because I think Dr. Eisen and I both agree that having the genome of a species is cool; and besides, it is a hard life studying microbes as compared to charismatic macrovertebrates.

    Point #3 is more interesting. I think Eisen knows, though, that (regardless of what I personally can or can’t be bothered with) if it was really the content of a paper that mattered rather than the journal in which it was published, we would have a culture that judged scientists solely on the quality, the content and impact of their work, rather than where it is published. Wouldn’t we? If those things were truly more important, wouldn’t those then be the sole characteristics that journalists would focus on as well?

    Jon, thanks for adding the point about your authorship on paper #4; I had intended that to be clear, but was perhaps too subtle. I hope none of my other intended points are too subtle. In the interests of full disclosure, I should also mention that I was an author on the finch genome paper and on the opossum genome paper (along with 70 or so of my closest friends on each), and that my former postdoc Wanjun Gu was on these papers, and on the recent panda genome paper. For the record (and on the more serious side), I hope people will take Jon and colleagues’ points about phylogeny-driven selection of genomes to sequence (paper #4) and apply them to future choices for animals as well as bacteria.

  17. Carl Zimmer
    April 6, 2010

    David [20]–I just want to point out that YAGS is, for me, a disease whose vector is journalism and press releases. Of course, genomes ought to be published in scientific journals. I just don’t see why the media need to give special attention to them in 2010.

  18. Sergy
    April 6, 2010

    Why special attention? Because you can! Because you have occasion to tell something about some interesting organism.

    [CZ: But who decides that there will be such an occasion? And why is that occasion so often the sequencing of a genome?]

  19. Jonathan Eisen
    April 6, 2010

    David, Carl, Sergy, etc — Writing here to address the last few points – will respond to David’s bait about publishing later.

    Regarding genome papers per se, I think many of these genome papers, mine included represent a strange hybrid between review papers and new discovery. Sometimes, the new discoveries in the genome papers are really interesting and important. But much of the time they are not. So they are cool in a way in that they represent a focus point for everything that is cool and important about an organism, or a branch in the tree of life. And in many cases, genome papers report really novel and interesting findings. But if I can restate what Carl sort of said in my own way – I think the issue with the 1000th microbial genome paper and the 50th animal genome paper and so on is not that the science is bad – the problem is that there is lots of good science out there and that genome papers have gotten a bit more attention than they deserve. Genome sequences are great – they are my scientific life blood. But lets not overhype them at the expense of other fantastically interesting stuff being done in genetics, cell biology, ecology, evolution, neurobiology, microbiology, etc.

  20. Damian McColl
    May 5, 2010

    [CZ: It is indeed amazing that scientists can now sequence entire genomes so quickly and inexpensively. But the sequencing of any one of those thousands of genomes is not cause for a lengthy article in a newspaper. The insights gained from studying that genome may (or may not) be a cause for one.]

    I’m just greatful that our newspapers bother to publish any science at all no matter how un-newsworthy you think it is. Genomes are lot more interesting and significant than most of the so called “news”. Why don’t write an article that synthesizes a lot of significant findings from individual genomes (and which you presumably find interesting) and submit that to the newspapers. I believe that is part of the “Carl Zimmer job descriptor”. Newspapers have limited space and so they tend to focus on short articles that most people may get in the 25 seconds or so they actually bother to read them.

  21. William Skyvington
    September 8, 2010

    Anybody (even an intelligent scientist such as CZ) has the right to declare that he/she has become blasé about such-and-such an aspect of scientific discovery and technological progress. But why make a public declaration concerning this lack of enthusiasm, as if it were interesting news? Countless individuals remain perpetually excited by the quest for knowledge… even when it’s simply YAGS stuff. Incidentally, that acronym is a typical specimen of smart-ass terminology invented by dull journalists.

  22. Burial Brishen
    August 21, 2012

    Even though this is an old post, I found this blog on Ask. This is a helpful post. I hope to see you remove the primary idea of this post and make a second post, and maybe include a video, also? If you do, it would be greatly appreciated.

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  6. Carl Zimmer on genome sequencing | AlbinoMouse

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