Thursday, August 30, 2007

Adaptationomics Award #1 - Wolbachia DNA sneaking into host genomes

Well, I have decided to start a new award. For years I have been fighting against the tide on the tendency for people doing genomics work to resort to silly adaptationist arguments for observations. The argument goes something like this. We sequenced a genome (or did some type of genomics). We made an observation of something weird being present (take your pick - it could be a gene order or a gene expression pattern or whatever). We conclude that this observation MUST have an adaptive explanation. We have come up one such adaptive explanation. Therefore this explanation must be correct.

Gould and Lewontin railed against this type of thing many years ago and others have since. Just because something is there does not mean it is adaptive (e.g., it could be neutral or detrimental). And even if something is adaptive, just because you can think of an adaptive explanation does not mean your explanation is correct.

And this is so common in genomics I have decided to invent a new word - Adaptationomics. And I am giving out my first award in this to Jack Warren Werren and colleagues for their recent press release on their new study of lateral transfer in Wolbachia (plus it lets me plug their new study which is pretty ^$%# cool).

Basically, in their study (led by a past colleague of mine from TIGR, the brilliant up and coming Julie Dunning Hotopp) they showed that there have been multiple lateral transfers of DNA from Wolbachia (which are intracellular parasites that can infect germ cells) into invertebrates. Furthermore they showed that that the DNA transfered to the host genome is not completely transient and that in many cases it is passed on to future generations. This is interesting because it is the first report of strong evidence for such "stable" transfers from bacteria into multicellular species. Of course, one could say that this finding is not that surprising given that Wolbachia infect germ cells and given that DNA transfer from organellar genomes to nuclear genomes is quite common. But Wolbachia are not organelles and since it appears that their DNA can readily move into genomes of multicellular species, this opens up a new window into our understanding of gene transfer.

This of course does not mean that the DNA is anything but "junk" in terms of functions in the host genome. And this is where the adaptationomics comes in. One of the press releases associated with the paper has a bit of an outrageous adaptationomics claim that I would like to counter. In response to their finding of a nearly complete Wolbachia genome in the nuclear genome of a fly Warren Werren says
The chance that a chunk of DNA of this magnitude is totally neutral, I think, is pretty small, so the implication is that it has imparted of some selective advantage to the host.
And Dunning Hotopp in a Nature article says:
The discovery also hints that the bacterial genome must have provided some sort of evolutionary advantage to its host. "You're talking about a significant portion of its DNA that is now from Wolbachia," says Julie Dunning Hotopp, a geneticist at the J. Craig Venter Institute in Rockville, Maryland, who led the study. "There has to be some sort of selection to carry around that much extra DNA."
This notion that the DNA MUST have an beneficial function is pure adaptationomics. Consider the movement of DNA from organellar genomes into the nucleus. Such movement occurs at an incredibly high rate and the DNA seems to be maintained in the host genomes for millions of years. For example, when we were sequencing the Arabidospsis genome, we found at least one if not more whole copies of the mitochondrial genome embedded in the nuclear genome and we concluded this was likely a non adaptive event. That is, the mt DNA was not conferring some advantage on Arabidopsis plants. There is extensive work on what are called "numts" (nuclear mitochondrial DNA) in humans and other species that makes similar conclusions - the mtDNA in the nucleus is basically junk but it is maintained for long periods of time. Sure, occasionally, the DNA confers some selective advantage. But this is a very rare event and one cannot infer that some DNA is advantageous simply because it is present. This is especially the case for eukaryotes which are generally more able than bacteria to maintain DNA that confers little selective benefit.

So I would argue that WarrenWerren and colleagues appears to have fallen for the adaptationomics trap - they want to believe these Wolbachia DNA inserts confer some selective advantage. But there is no need to assume this simply because the DNA is there.

Anyway - as is the case more and more. Read the paper. Ignore the interviews and the press releases.

19 comments:

  1. I can't parse: "Basically, in their study that can infect germ cells, DNA transfer may be almost as common as is seen for (led by a past colleague of mine from TIGR, the brilliant up and coming Julie Dunning Hotopp)..."?

    Does adaptationomics subsume the field of evolutionary psychology?

    What do you think of _Genes in Conflict_?
    http://books.google.com/books?id=_XPtp_mtqUQC

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  2. Sorry - my editing somehow moved around half sentences in bizarre ways. Hopefully it is clearer now -- I edited a bunch of things (although Blogger annoyingly does not have an easy way of tracking changes so you cannot see what was changed - just the new text).

    And yes, adaptationism is rampant in much of evolutionary psychology. So presumably when they use genomics in that field, there will be excessive amounts of adaptationomics.

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  3. Hi!

    A (silly) question:

    I do understand that horizontal gene transfers are not necessarily a benefit to the genome recipient, thus won't be under selective pressure. But yet these neutral events are a still a gain of genetic material that can give rise to new functions, novel genes? Maybe allowing the organism , much after the event, to adapt itself to new environment challenges?

    Cheers!

    Mookie E.T.Shea

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  4. Sure lateral transfers, even if they start out as neutral could lead to new functions. And almost certainly do. But (1) gained DNA does not have to be adaptive to initially spread into a host population (I think in bacteria, non beneficial DNA will get eliminated much more rapidly and thus is less likely to spread into the population) and (2) the initial introgression of DNA can be a random event. Warren even says this in the press releases. The only disagreement I have is this notion that there MUST be some functional benefit conferred by the DNA

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  5. Thanks for the link to my story, Jonathan.

    Does gene expression, however low, suggest that at least some of these genes are being selected for?

    Ewen

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  6. No. Gene expression alone is no indication of positive selection. It could be totally spurious.

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  7. A test of whether there is selective constraint on the inserted copy would be helpful in judging whether the insertion provides some function. A lack of constraint would imply that the insertion was neutral. This could be done by comparing nonsynonymous and synonymous divergence, between the inserted sequence and the Wolbachia (Ananassa and Mel). I'm surprised they didn't do this to support their claims of selection, but perhaps I missed something on my quick read through the paper.

    Graham Coop

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  8. Yes, they could have done something like that. Maybe they are doing that now.

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  9. PS congrats on your book coming out, I look forward to reading it.

    I'll see you in Davis sometime soon as I'll visit to prepare for my move.

    Graham

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  10. Looking forward to you being out here. Though I am at some point going to have to go through the book again and award us some adaptationomics awards as, though I tried to go through everything and make sure we did not fall into the adaptationist trap I am sure we did do it some.

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  11. Hi Jonathan,

    I heard that you were calling me bad names, so had to check this out.

    First, let me say that I am fully aware that many features of the genome are not at all adaptive and I am quite familiar with the concept of genetic drift. For a feature to increase significantly by drift, it will need to be neutral or very mildly deleterious in heterozygotes, and to go to fixation it will need to be neutral or effectively so (i.e. depending on population size)also in homozygotes.

    The basis of my remark about the ~1MB insert into D. anannassae is that I am skeptical that an insertion of this magnitude will be nearly neutral. This is conjecture on my part. We will see if it is correct.

    There is also a missing piece of information in the report. We have indirect evidence that the insert could be strongly deleterious in homozygotes (we have not yet proven that the effect is due tdirectly o the insert itself). If this is so, then given that the insert is so widespread and common, it would have to be selectively favored in heterozygotes.

    Thank you for your delightful award.

    Jack Werren

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  12. Thanks for the update Jack. I figured there was more behind the scenes than made it into the paper and press release. And your welcome about the award --- as I said above, I am sure I deserve some of these too and will have to give a few to myself.

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  13. Hi Jonathan

    I think the concept is interesting. However, seems the selective pressure in the host and the consequences of these events require a careful examination. In 2004 it was reported that approximately 492 aa of an ORF related to the polymerase of the Cell Fusing Agent and Kamiti River virus was inserted in the genome of mosquito. So far the discussions seem to assume insertion equals new genes or proteins with new functions. However, these events might lead to other types of molecular control such as siRNA that may lead to selective pressure in different regions of the genome.

    Cheers

    Willy

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  14. I think evolution is just the idea that some people are only interested in things that are alive, and the shorter period of time something is alive the less interested an evolutionist is in the item.

    Hope that doesn't kill the Blog post.

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  15. Julie Dunning Hotopp9/04/2007 8:19 AM

    Thank you for the compliment Jonathan—-it almost mitigates all the pain and agony of your award and the accompanying barrage on other blogs.

    I think you were fair, but I do wish your blog had further emphasized the last point. Of course, I understand why your emphasis is on the evolution aspects. But I do think that any scientist who wants the real science, should read the paper and not the news articles. Reporters take snippets, and do not tell the entire story. I view the purpose of these stories as ranging from alerting scientists to papers they should read to conveying an interesting story to mom and dad. Unfortunately, that does lead to oversimplification. And if you don't read the paper, you'll never know about the amazing Dirofilaria immitis story discovered by Jeremy Foster--that story isn't in any of the press release. And besides, this was my first interview. Give me some slack!

    I think there are much more egregious errors in these stories (of course I’m not responsible for those). For instance, it should be a larger concern to scientists when the Science news story reports in the caption to the figure, “Scientists knew they had found bacterial genes (in yellow, left) inside a developing fly egg, because treating the ovary with antibiotics erased that DNA (right).” I never knew you could cure an organism’s DNA with antibiotics.

    I do think (hypothesize) there has to be some selection, either positive or negative. I can’t prove it; so its not in the real paper. You just cannot make that many nucleotides over and over again, and it not be a drain on the organism. It might be a small drain, but still a drain. And like Jack, I have access to data not presented in this manuscript. But of course, that is cheating.

    Oh, and to the person asking about a dN/dS comparison. The different Drosophila ananassae sequences are too similar—which is presented in the paper. This would be more interesting for the Brugia sequences, which are older. But since we can’t cure the nematodes of Wolbachia infection, I worry that relying on sequences amplified from Wolbachia infected material would not be robust.

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  16. Thanks for the post Julie and if I had known the award would have run away from me like it did, I would have tried to pick something else, since the science here was so cool, and since, well I worked with you and like you.

    A few points though ... if you want the public to read the original science, you should publish in Open Access journals so they can read it. Otherwise you are in fact left to the reporters and the quotes for everything. Cutting off the public from the actual science is a bad idea and the problem with journals like Science, etc is that they are cutoff.

    As for the selection, I picked your quote because in fact I disagree with you. When sequencing euk. genomes we and others have found them littered with organellar DNA. I think most if not all of this can be thought of in the same way as mutations -- usually either detrimental or neutral and only rarely positively selected (your quote implied positive selection, not negative selection). I think because Wolbachia infect germ cells we can view them in some ways like organelles and thus I would stick with them as the model for now. As for making that many nucleotides, I do not buy that argument at all ... introns cost the cell much more energy than any extra DNA since introns are made over and over and over again. But they are still there.

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  17. Julie Dunning Hotopp9/04/2007 12:43 PM

    Science did provide me with one link where anyone can download the paper for free. So everyone has access to the paper, so they have no excuse not to read the paper. It will be on my website shortly (and then will move with me when I move to UM SOM).

    When I made the comment, I meant that I doubted it was neutral, but that it could be either advantageous or disadvantageous. I think people jump to thinking that I meant advantageous. But I didn't.

    We assume that mitochondrial fragments and introns have no function. But who knows, maybe they do. I'm open to the possibilities.

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  18. Well, Science providing you with a link for the PDF that people can get if they are fortunate enough to find your website is simply not my idea of open access. If that is the equivalent, then they should just make everything for free on their site. They know full well that few people will find it on your site.

    As for the selection, what I based my inference on was your statement in the Nature quote "There has to be some sort of selection to carry around that much extra DNA." That implies positive selection was required to keep the DNA there.

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  19. To Willy - I think there are 1 x 10^6 ways that foreign DNA might end up influencing a host. And yes, siRNA is one. I also agree that coding potential is one of the last things to think about ...

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