The interesting genomes are almost gone!

Sep 29 2010 Published by under [Biology&Environment]

So I was minding my own bloggy business the other day and ran across a link at the John Hawks weblog to the discussion we were having the other day about press announcements pre-empting publishing. While reading, I came across this gem:

I think genomics has come to an inflection point -- organisms whose genomes are obviously of some utility, but which have not yet been subject of a whole-genome sequencing project, are getting scarce. It's not enough to sequence a genome, if you want to do glamor science. You have to have some, you know, science in there -- pushing theoretical understanding in some way.

I was going to leave a comment there, but it's one of those comment-free monoblogues, so we can discuss this here instead. Whereas I agree with the second part about needing to find something interesting in a genome and do a thorough analysis to get it into a glamor journal, the first part is what made me stop and say "WUT?" This is the kind of stuff that drives me nuts, as I have mentioned before because what is really meant is that we're running out of 'interesting' animal genomes to sequence. If you ask me, we hit that point a while back, but there are a shit-ton of interesting genomes out there we have virtually no idea about.

Depending on who you believe*, there are probably 5-7 'supergroups' into which all eukaryotes can be classified. Of those groups, 2 (or 3, again, based on classification scheme) have not a single published genome sequence and many major lineages within those groups are also unrepresented. We have few or no genomes to use when investigating some of the major innovations in eukaryotic evolution. We know virtually nothing about ecologically important (and truly bizarre) organisms, like dinoflagellates, at the genomic level. To say that interesting genomes are getting scarce is to admit that your view is "if it ain't animal, it's crap", which is a pretty sad statement for a biologist.

I'm not suggesting that we all go out and find a bizarre beast to work on, but simply that we allow for the possibility that there is important science happening outside of animals (and even plants, on a bad day). There is even the chance (though not a requirement) that the discoveries in Other organisms could advance the science in animals. You never know what unusual cell might change the way we look at fundamental cellular processes.

Hey there, I'm Tetrahymena. We probably haven't met, but there have been dozens of critical discoveries made using me as a study subject, including Nobel Prize winning research catalytic RNA and telomerase. But, you know, whatever. Oh, did I mention I have two nuclei that are different forms of essentially the same information, but function completely differently? Other than all that, I'm boring as hell.

*The fact that there is active debate on the major groups of eukaryotic organisms should be half decent evidence that we need to more broadly sample organisms rather than sequencing 1000 of the same genus.

17 responses so far

  • Dan Gaston says:

    Thanks for this post. As a PhD student in one of the research labs contributing heavily to the Eukaryotic supergroup work (excavates in particular), it's nice to see someone beating me to the punch on making this point. There is just so much we don't know about eukaryotic diversity, let alone diversity in general once we include all of the Bacteria and Archea. We aren't in danger of running out of interesting genomes to sequence anytime soon. Compared to that background animals are a relatively small group of organsims with very little genomic diversity.

  • David says:

    I completely disagree with the sentiment that "all the good genomes are taken" for one major reason - organism diversity. Large-scale studies of genome landscapes within large taxonomic assemblages are of great importance for our basic understanding of genome biology. To date however, the major focus in generating genome drafts for eukaryotes has been on obtaining taxonomic breadth. Unfortunately, such a broad sampling has led to cases in which a single species comes to represent an entire assemblage of diverse organisms (e.g. Anolis carolinensis for all squamates; Xenopus for all anurans; and, until recently, Gallus for all birds, etc.).

    Thus, one runs the risk of drawing inaccurate conclusions about the group when observations may actually be unique to that one taxon rather than the group as a whole. In other words, one significant drawback to this approach is that there is a substantial danger of overgeneralizing and a lack of appreciation of the diversity in certain groups of organisms.

    For example, what does it mean to be a squamate from a genomic perspective. The only squamate genome to be sequences so far is Anolis carolinensis. Does this mean we should take only this taxon's word for it? Does understanding the Anolis genome mean that we automatically understand geckos, or iguanas, or snakes? I don't think so. If we want to understand what it means to be a lizard in a general sense, it makes no sense to look at only one lizard. As an analogy, would you want the alien visitors to select a single human (say, Sarah Palin) and generalize to all humanity?

    As a scientist I'm big on getting second (third, fourth, fifth) opinions. Forgive the animal-centrism.

  • If we're really truly running out of "interesting" genomes (singular entities) -- and I do not think we are -- then it's time we turned to focus on metagenomes.

  • theshortearedowl says:

    I think genomics has come to an inflection point — organisms whose genomes are obviously of some utility, but which have not yet been subject of a whole-genome sequencing project, are getting scarce.

    Yeah, and in the future we'll only need 4 computers for the whole world.

    What he means is "waah, I can't guarantee a paper in Nature just cos I sequenced a genome anymore, waaahh!!" Well what do you expect? When I was an undergrad, one of my professors related how he did his whole PhD sequencing one gene. Try and even get a paper out of that any more!

    Come on people! Genomics is just getting interesting! There's not much you can do with just one genome - but soon we'll have lots! Lots of different but related species, lots of the same species, one of every major group! Woohoo!

  • Dan Gaston says:

    David: If we look through sequenced eukaryotic genomes on a supergroup basis I think we'll find that the Metazoans are one of the most extensively sequenced groups out there. Metazoans + Fungi even more so. Probably the next runner up would be Land Plants, at least there we are starting to get further away in terms of taxonomic breadth. The problem is that when we talk about genome diversity we are really talking about two different (but both important) things when we talk about depth versus breadth.

    Why are different animal lineages different from one another? Well, it seems to me that most animal lineages are different from one another, genomically, in very different ways from say two distantly related protists within the Excavata or Rhizaria for instance. Given any two protists sampled from the Eukaryotic supergroups that aren't primarily multi-cellular organisms (ie not Metazoans or Fungi), they are likely to differ hugely in their actual gene content, genome size, whether they are aerobic or anaerobic, have very different functioning organelles (aerobic mitochondria versus a hydrogenosome or mitosome), etc.

    If we look at multi-cellular organisms these genomic differences will either be absent or be far more subtle. What we will observe though will be more variations in regulatory sequences, copy-number variations, etc (please correct me if I am wrong). They are both important to understand, but for different reasons.

  • [...] This post was mentioned on Twitter by Bora Zivkovic, Fred and Howard McLeod, ScientopiaBlogs. ScientopiaBlogs said: The interesting genomes are almost gone! [...]

  • I want a passenger pigeon genome.

    Just saying.

  • Isabel says:

    We actually don't have many plant genomes and the ones we do tend to be crop plants, all from the same group, angiosperms. Many major groups, such as ferns, do not have a single genome. We also do not have a charophyte genome, the closet algal relatives of land plants.

  • proflikesubstance says:

    'Many' is all relative. Like I said above, there are major lineages (think plants + green algae + red algae + glaucophytes, which are all in the same supergroup) that have no published genomes (yes, some are being worked on). So the fact that there are > 20 genomes in the lineage you are concerned with, is again, a relative paucity. Relative only to animals.

  • [...] The interesting genomes are almost gone! [...]

  • John Hawks says:

    Hey, thanks for picking up this topic!

    I completely agree -- you describe many of the reasons why genomics is important and interesting, while genomes themselves are boring.

    It seemed pretty transparent from the reporting on the Tasmanian devil genome rush that many sequencing projects are looking for the easy score -- charismatic species, little science beyond press release and sequencing runs necessary. And that just doesn't cut it anymore.

    I'm a little sad that the reason isn't the journalists got wise, but that they've run out of charismatic species.

  • Seeing the title, I was mentally getting ready to rant VERY LOUDLY in the comments. Luckily, I read the post instead. You see, I happen to occasionally occupy space in a lab that does plenty of genomes, of really booooring organisms like super-reduced microsporidia and things with tertiary plastid endosymbiosis and such. I'm sure they'd all agree that there's nothing interesting left to sequence, and we know everything there is to know about life. I mean, primordial ooze like Amoeba dubia can't -possibly- have a large and complex genome, can it? And I'm sure dinoflagellate genomes are about as diminutive as the cells themselves. Even their chromatin structure is freaking boring and not weird in any way whatsoever, and did not lead to them being called 'mesokaryotes' at one point...

    To me, shit like the apple genome or whatever is boring as hell; Naegleria or Reticulomyxa, or Joenia, on the other hand, is/would be freaking -amazing-. Oh what I'd give for a complete foraminiferan genome... some of them also have nuclear dualism, like ciliates; except, unlike ciliates, no one has yet gotten around to examining the molecular biology of it.

    To add to Dan's comment, there's also VASTLY more diversity in cellular structure among non-Animal-Fungal-Plant eukaryotes. Multicellularity tends to result in cells getting bland and stupid, as there's many of them and sloppiness in each one (ie, loss of various structures and processes in diff cell types) is tolerated. A unicellular organism must be entirely self-sufficient, and thus selective pressures to maitain a 'better' cell are much stronger. Overspecialisation leads to enabled degradation of the individuals not only in terms of education and training of human beings!

    @Prof-Like Substance
    I think the major problem here is that most people, ranging from laypeople to students to faculty, have absolutely no idea how limited, outdated and outright wrong their view of biodiversity is. Some subdisciplines are worse than others, with some published peer-reviewed papers ion "high" journals (lol) still work under the assumption that plants, animals and fungi share a common origin of multicellularity, sometime shortly after yeast (ironically, yeasts are secondarily unicellular, lulz). Just recently, our only-slightly-outdated textbook showed the Whittaker '63 five kingdom classification diagram as if it's even marginally relevant outside history of science classes. With only a casual mention of Three Domains, because, y'know, bacteria are boring and irrelevant and stuff. The worst part was the relative abundance pie chart, with 75% of it being animals, and "monera"+"protista" sharing the last 5%. Most people see nothing wrong with that. Most journals don't either.

    And "You never know what unusual cell might change the way we look at fundamental cellular processes." would be my overall research statement in a sentence 😉 Very seldom do protists, for example, get any credit for their contributions (well, their scientists' contributions too) to cell biology. Haptophytes were instrumental in deciphering the workings of the Golgi, due to their amazing coccolith secretion story. Forams were key in realising that the cytoskeleton is actually a highly dynamic structure, due to their awesome reticulopodial system where unusual alterations of tubulin allow for a 10x increase in polymerisation speed compared to the rest of the eukaryotic domain we know of. Do either of those get mentioned in undergrad textbooks? Not really.

    I'm very happy that someone outside our tiny field agrees with that sentiment =D Some faculty convey this aura of "I don't need to know any of this for MY research, because MY research is too awesome for facts". My fellow students typically give me the "oh so you wanna work on primitive slime" look and proceed to brag about how they're applying to Bigshot's lab and had the high honour of making eye contact with Bigshot's student's student. Yeah, well, we may not have many Bigshots, but at least our field is awesome, both in terms of research and in personal attitudes of its members. Dan would probably agree, right?

  • theshortearedowl says:

    That situation is changing; there is a great resource for plant genomes both published and in progress here:

    Plant genomes are often problematic; how do you provide a definitive sequence of something that has variable ploidy? That set the maize genome project back years.

    But yes, we need more non-angiosperms. This is exactly what I was saying though - the interesting bit comes when we have enough different genomes to really start piecing together their evolution, at population, species and higher levels.

  • theshortearedowl says:

    Please! Orchids? Leatherback turtle? Blue whale? Anyone else want to play?

  • Isabel says:

    If you are referring to my comment about plants, I think the link the shorteared owl provided (thanks!) proves my point. I absolutely agree with you about the other super-groups, but from the same objective (non-anthropocentric) evolutionary point of view, the plant choices have been very frustrating, i.e. only two completed non-angiosperm genomes in the entire green plant lineage that includes the land plants! The greening of the terrestrial earth, one of the major chapters of evolution of life on earth, was a done deal long before angiosperms appeared on the scene. The reason we have so many angiosperm genomes is obviously related to the same human bias that brought us the large number of animal genomes. So I think it's the same problem you bring up in the OP but on a different scale. To those interested in land plant evolution in general, how helpful is 20+ genomes from a single derived clade?

  • Dan Gaston says:

    @PsiWavefunction Agreed, although I think we have bigshots, they just aren't people known outside of a relatively moderate sized scientific community. Also, almost all of them, are awesome and kickass. Its nice to know I can go to a conference and walk up to our Bigshots and strike up a conversation as a student, or buy them a beer in a pub.

    One thing I always like to keep in mind, that my boss has said a few times in regards to Mitochondria and related organelles, is imagine what science textbooks would say about "typical" mitochondria if we had of picked a different model organism to work with than say yeast. What if we had of looked at Trypanosomes instead and aerobic mitochondria where thought to be the oddball? The view, outside of say protistology and some molecular phylogenetics, of biological diversity is heavily skewed by the past choices in model organisms.

    @John Hawks: I would still disagree with you on your statement of individual genomes being boring. YAGs (Yet Another Genome) of very closely related organisms in relatively well studied lineages (like Animals) that exhibit very little novelty in their genomic content are pretty damn boring and uninteresting. But fortunately that just isn't true for the vast majority of unicellular organisms. Or even some multicelluar ones. Sequencing the Ectocarpus genome was exciting because it is the only representative for another lineage with an independent origin of multicellularity. If we sequence a Foram or Apusozoan it will be exciting because nothing like it has been sequenced before.

  • Heavy says:

    I feel for you all. I have literally hundreds of genomes to work with in a single genus.....

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