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Tuesday, November 07, 2017

Lateral gene transfer in eukaryotes - where's the evidence?











  1. Readers might want to know that Martin suggests that eukaryote LGT claims are fundamentally Lamarckian, whereas prokaryotic LGT claims are not.

    1. Some scientists suggest that eukaryotic anaerobes took on bacterial genes (by LGT) in order to survive in an anaerobic environment.

      Martin points out several flaws in this argument. He demonstrates that sets of multiple genes would have to be inherited as modules in order to confer selective advantage. He also points out that the evidence does not support this hypothesis.

      In addition, and almost as an aside, he says ....

      Looking at the matter openly, the claims that eukaryotes acquire genes from anaerobes and then inherit them so that progeny may survive in anaerobic habitats are completely Lamarckian in the terms of what biologists today associate with Lamarck ...

    2. Fair comparisons of LGT in prokaryotes vs. eukaryotes cannot properly be done at the moment because there are thousands of complete and closed prokaryotic genomes sequences, but there are very few completely sequenced eukaryotic genomes. It is quite premature to conclude that eukaryotes (mostly unicells) don't acquire genes laterally often and continuously.

      Logically, there is no reason to preclude this. Unlike animals, most eukaryotes don't separate germ from soma, most eukaryotes are unicells--protists. Eukaryotic genomes are constantly invaded by viruses and all other kinds of mobile genetic elements (as it is overwhelmingly well documented). These are known to move around all kinds of genes with them. Many eukaryotes are phagotrophic, which means that plenty of DNA is released in cytosols, like when organelles are lysed (the source of EGT). Plenty of protists also harbour endosymbionts, most of which are constantly digested releasing DNA. Conjugation between prokaryotes are eukaryotes is well known. The conjugative plasmids can carry many genes with them, as we know happens in prokaryotes.

      The coming years will certainly provide a much clearer view on this issue. Complete eukaryotic genomes (from telomere to telomere) can now be cheaply sequenced combining long- and short-read sequencing techonologies. But it is a mistake to dogmatically take a strong position in this debate. The current data are contaminated for sure, but also too scarce and incomplete.


      It's not just lamarckian, it makes it seem as if eukaryotes somehow "know" what they're doing and which genes to "take" from prokaryotes, because they are somehow "aware" that these genes will be useful to their descendants in the future.

      As everyone should know, that's not how evolution works. The Watchmaker is blind!

  2. I don't have references ready but over the years my impression was that there is tons of evidence in fungi and protists. Vaguely remember a paper on Phytophthora infestans where a marker from one strain made it into another - all within one season in a single field of potatoes.

  3. what about

  4. The evidence for HGT from prokaryotes to eukaryotes is compelling

    1. I think there's a difference between endosymbiosis and lateral gene transfer. Not everybody agrees. Anyway, the point in Larry's opening post is about the claims for tad more recent LGTs, which, for humans, seems like a rather hasty conclusion.

    2. @ Gabriel:

      But you did not describe the thrust of this exceptional article.

      The authors describe a Eukaryote's complete loss of the Mitochondria and an enhancement of substrate level ATP synthesis by co-opting genes from anaerobic bacteria

      Their findings seem sound enough Tommy jaundiced eye

    3. Yeah. I should not answer in haste.
      Interesting paper. Thanks.

  5. Of course the same arguments as to why eukaryotic LGT is rare can also be applied to the rather credulous claims of rampant LGT in bacteria and archaea. LGT anywhere is not unlike selection in that it should be the absolute *last* explanation when other explanations have been ruled out, not the go-to explanation for anything.

    1. I agree. I think LGT occurs in bacteria but not to the extent claimed in the scientific literature.

      I'm pretty skeptical of those massive pangenomes.

    2. This won't be the last word on this subject...stay tuned. Meanwhile I suggest going to PubMed and searching for Wolbachia and horizontal gene transfer in insects and nematodes. Pay close attention to recent findings in pillbugs. Then search for papers on the origin of genes in giant viruses of eukaryotes. Then search for papers on remnants of giant virus genomes in eukaryotic genomes. Then search for papers documenting conjugation between bacteria and eukaryotes. After reading these papers, then re-read what Martin has said.

    3. @ajames roger

      There are two issues here. The first is whether Bill is right about claims of abundant LGT in eukaryotes. Do YOU think typical eukaryotic species contain 100-200 new genes recently acquired from bacteria by LGT? If not, what do YOU think is a reasonable number?

      Martin is not denying that LGT exists in eukaryotes ... he's just questioning whether it's rare or abundant.

      The second issue is his critique of your papers. Martin's main argument against abundant LGT is that we don't see accumulation in lineages. I think that's a good argument.

      He recognizes that you (and others) have a counter-argument that accounts for this lack of accumulation. He calls it "lateral late." It's the idea that many genes may have been borrowed from bacteria relatively recently so they don't show up in extensive clades.

      His critique of your papers raises some interesting questions. Do you care to respond?

    4. I'm posting this in two pieces:
      @Laurence A. Moran

      You said:

      “There are two issues here.”

      There are far more than two issues here, but I’ll get to that in a minute.


      This sounds like a simple question to answer but it is not. It is really critical to define what is meant by “recently acquired” in this context. How are we deciding whether or not a given gene in this species was recently acquired? Can a sister species or strain have it too? In the end, different studies reporting LGT use different criteria to define what they will count as an LGT into the genome of a species (this happens in prokaryotic genomic analyses too, by the way). Because eukaryotic genomics lags behind prokaryotic genomics in terms of the number and density of genomes sampled from eukaryotes, it is often the case that new species whose genomes are sequenced can be distantly related to other eukaryotes whose genomes have been characterized and hence the numbers of genes reported from this genome to be derived from LGT (and not shared with other genomes characterized) is relatively large. This doesn’t necessarily mean the rate of LGT is very high – which is the real question we want to answer.

      Attempts to actually quantify rates of LGT into eukaryotes are hampered by the fact that, outside of animals, the sampling breadth and density of high quality eukaryotic genomes is pretty low. However, it has been attempted in Fungi using rigourous methods (see: Szöllözi et al. (2015) Philos Trans R Soc Lond B Biol Sci. 370:20140335)

      In any case, I think it is entirely reasonable that for some genomes of eukaryotes that are distantly related to other sequenced eukaryotes, that we will see 100-200 genes derived by LGT from bacteria. Of course, once genomes of closer relatives of that organism are sequenced, then we will see that some of them share some of these LGTs and some do not…the expected pattern of gains of traits over a phylogenetic tree. This is precisely what we, and others, have reported (see Eme et al. (2017) Curr Biol. 27:807-820, Vikeved et al., (2016) PLoS Negl Trop Dis. 10:e0004326).

      “ If not, what do YOU think is a reasonable number?”

      As I said above, I don’t think this is a very sensible question because it depends on how closely related is that genome to other characterized genomes and how you count the LGTs. The more sensible question is what is the rate of LGT per unit time. That likely varies greatly over eukaryotic groups. Metazoans with sequestered germlines probably have a much lower rate than some protists or Fungi, for example.

      I note that neither you nor Bill Martin actually provided a clear statement of what IS a reasonable amount of LGT in eukaryotes to expect.


      Ah yes, the old ‘shifting goalposts’ phenomenon. In the first page of Martin’s Bioessays piece he poses the question: “Could it be that eukaryote LGT does not really exist to any significant extent in nature, but is an artefact produced by genome analysis pipielines?” The implication of his article is that the answer to this question is “Yes”. But Martin leaves himself wiggle room by saying he doesn’t deny that LGT in eukaryote ever happens.

      In Ku and Martin (2016) BMC Biol. 14:89, the following statement is made: “Our analyses indicate that eukaryotes do not acquire genes through continual LGT like prokaryotes do.”
      That sounds a lot like saying it doesn’t happen at all. But then, if someone (like me) starts to point out the Wolbachia examples, or other insect examples (e.g. Moran and Jarvik (2010) Science 328(5978):624-7; Husnik and McCutcheon (2016) Proc. Natl. Acad. Sci. USA), or the very abundant examples in fungi (e.g. Ropars et al. (2015) Curr. Biol. 25(19):2562-9) and the dozens of well documented cases in protists, then the reply is: “Martin is not denying that LGT exists in eukaryotes”. This is a clever rhetorical device, but I’m not sure it is a very constructive way to move forward.

      In any case, you state in your blog (as Bill says in his article): “Second, there’s no reasonable mechanism for LGT as there is in bacteria”

      This is false. Mechanisms mediating LGT in eukaryotes are well documented and include natural transformation, conjugation between bacteria and eukaryotes, cell fusion, viruses that can carry phylogenetically diverse collections of genes, and, DNA acquisition from endosymbionts.

      Here are some references:
      1) Nevoigt, E., Fassbender, A. & Stahl, U. Cells of the yeast Saccharomyces cerevisiae are transformable by DNA under non-artificial conditions. Yeast 16, 1107–1110 (2000).
      2) Lacroix, B. & Citovsky, V. Transfer of DNA from Bacteria to Eukaryotes. mBio 7, (2016).
      3) Soanes, D. & Richards, T. A. Horizontal gene transfer in eukaryotic plant pathogens. Annu. Rev. Phytopathol. 52, 583–614 (2014).
      4) Filée, J. Multiple occurrences of giant virus core genes acquired by eukaryotic genomes: the visible part of the iceberg? Virology 466–467, 53–59 (2014).
      5) Dunning Hotopp et al. Widespread lateral gene transfer from intracellular bacteria to multicellular eukaryotes. Science 317:1753-6 (2007)


      Except that it completely ignores the literature on ancient and recent LGTs in eukaryotes. It might be worth reading Szöllösi et al. reference given above and Richards et al. Plant Cell. (2009) 21:1897-911 and Soanes & Richards (2014))


      That is a mischaracterization of our arguments. I suggest reading:

      1) Leger, M. M., Eme, L., Hug, L. A. & Roger, A. J. Novel Hydrogenosomes in the Microaerophilic Jakobid Stygiella incarcerata. Mol. Biol. Evol. 33, 2318–2336 (2016).
      2) Stairs, C.W., Leger, M.M. & Roger, A.J. Diversity and origins of anaerobic metabolism in mitochondria and related organelles.Philos Trans R Soc Lond B Biol Sci. Sep 26;370(1678):20140326. doi: 10.1098/rstb.2014.0326. (2015)
      3) Roger AJ, Muñoz-Gómez SA, Kamikawa R. The Origin and Diversification of Mitochondria..Curr Biol 27:R1177-R1192. doi: 10.1016/j.cub.2017.09.015. (2017)

      “His critique of your papers raises some interesting questions. Do you care to respond?”

      The most interesting question it raises – a question that everyone should be asking -- is why is Martin so strongly opposed to the idea of LGT in eukaryotes?

    6. Martin and Salzberg's excellent critiques of genomic contamination notwithstanding, I found it very difficult to say that "horizontal transfer is rare" in eukaryotes. There are lots of good examples, and according to the Lynch & Conery genome theory TEs and other genomic parasites, often originating from other species, are actually to blame for very large fractions of the genome (introns and intergenic regions, for example). We reviewed data briefly for our paper "How reticulated are species?"

      For genes, how about the yellow gene family? Only found in insects and prokaryotes, according to this paper. Ferguson, L.C., Green, J., Surridge, A., & Jiggins, C. 2011. Evolution of the insect yellow gene family. Molecular Biology and Evolution 28:257-272.

    7. @jas
      I agree with your comments except for the point where you say "Martin and Salzberg's excellent critiques of genomic contamination...". I think everyone in the field more or less knew about the 'tardigate' contamination and the Salzberg take-downs of human genome LGTs. Much of Martin's article is not aimed at known cases of contamination; it is suggesting that contamination is a widespread 'cause' of false eukaryote LGT inferences. He is suggesting that a very large number of researchers in this field have made demonstrably false claims.

  6. How is this relevant for the claim a few years ago that eukaryotic genomes are roughly equal fusions of a bacterial and archeal genome?
    Martin isn't saying the prok to euk HGT never occurs its just rarer than everyone else is saying, though I wouldn't have thought ~100 prokaryotic genes in a eukaryotic genome is very many.

    1. ((should have read LMs last comment before posting this! ))

    2. Bill Martin has a nice paper showing that eukaryotic genomes are largely bacterial, and owe little to Archaea (except "informational" genes). Can look it out if you'd like. But these bacterial genes may largely derive from the initial mitochondrial endosymbiosis; it's not clear.

  7. (Larry said) Do YOU think typical eukaryotic species contain 100-200 new genes recently acquired from bacteria by LGT?

    If there are 100-200 new ones for each eukaryotic species, that is a huge number as it would pretty rapidly become the origin of most genes. And then those would be in turn replaced.

    I think one has to specify how new is "new". Perhaps Bill Martin does.

    1. @Joe Felsenstein
      Exactly! This is the point of my first paragraph in post above. This is really a question of the rate of gene gain by LGT per unit time. BTW, Bill Martin does not specify his expectations about this in the article, only that current reports are 'too much'.

    2. @ajamesroger: You're right-- I should have read that comment more closely, you nailed it.

      (I'll have fo tell the molecular evolutionist Andrew J. Roger that soneone here is using his name as a "handle").

    3. @Joe Felsenstein
      He already's me!

    4. The Web of Life

      Are there two different origins of life?

      The Web and the Net?
      Or, are they the same thing? Do they replace the old Darwinian tree of life some here still hold on like grim death?


  8. Hi Joe, you have to read the pape, not the blog. Try page 3.

    But let’s give those genes the full benefit of doubt as LGTs, and call the 0.5% values in Figure 1 real. A Drosophila genome has
    about 15 000 coding sequences. At 0.5%, that means 75 LGTs per
    genome. Now let’s assume that they entered the fly lineage about
    70 million years ago, just before divergence. Rounded, that is a
    convenient one-new-gene-via-LGT-per-million years, as a rough
    and conservative estimate on the rate. Recall that if we assume
    any of those acquisitions occurred during Drosophila lineage
    divergence, the rate just gets higher. For comparison, an old
    conservative estimate for the Escherichia coli rate was 16 kb per
    million years.[37,38] “Aha” say LGTproponents, the eukaryote rate
    is about 20 times lower than that of the prokaryote: everything is
    fine. No, nothing is fine.
    At a rate of one gene via LGT per million years, different
    lineages of animals that trace to the Cambrian explosion[39]
    should have acquired 700 different prokaryotic genes each.
    Furthermore, different major lineages (supergroups) of eukaryotes
    are about 1.6 billion years old,[39] so each supergroup
    should have accumulated 1600 different prokaryotic genes each
    because the LGT mechanism should produce lineage specific
    cumulative effects, just like sequence divergence does. Do we see
    eukaryotes acquiring new prokaryotic genes in a lineage-specific
    manner? Do we see a cumulative effect? No.

    1. Bill, I agree. In fact that was my point: even very low rates of ongoing LGT would lead to numbers of cases of LGT far greater than what we see. The typical eukaryotic reproduction event involves no LGT, and although LGT does exist in eukaryotes, it must be at a very low level.

      I'll leave you and Andrew to argue about how close to zero it really is.

  9. Dear Andrew,

    Shifting goalposts? Read the literature. The following quote is from Embley and Martin (1998) A hydrogen producing mitochondrion. Nature 396:517-519.

    "One view is that the genes were acquired by eukaryotes through horizontal gene transfer from one or more prokaryotic
    donors, other than the antecedent of mitochondria. If this were the case, the genes for these pathways in anaerobic eukaryotes should trace to different prokaryotic (eubacterial
    or archaebacterial) sources. An alternative view is that the eukaryotic genes involved in anaerobic ATP synthesis were
    inherited from a single common ancestor of mitochondria and hydrogenosomes. These genes are thought to have been transferred to the host’s chromosomes, because they are
    not found in any known mitochondrial genome. In this case, the common ancestor of contemporary eukaryotes would have
    acquired, from a facultatively anaerobic protomitochondrion, a genome’s worth of genes for all-purpose survival. These genes
    were then left to the workings of selection and common descent. From this we can predict that, across the anaerobic eukaryotes in Fig. 1, each gene should ultimately trace to a single eubacterial source."

    We can confirm: The goalposts are stable.

    If the world of adaptive eukarote LGT, proponents need to explain why it is always the specific genes that are acquired to provide the needed trait (Lamarckian genetics). In prokaryotes, genes are acquired at random from throughout (largely) random donor genomes, which is why pangenomes appear (a cumulative effect). In eukaryotes, the adaptive LGT dogma is "acquire at will and as needed", I will not finish the sentence with suggestions regarding "as needed by whom and for what?" I have been waiting for 20 years to see cumulative effects. I have waited long enough. They are not there. Its time to say so.

    One can always argue like a lawyer or (an intelligent design proponent) and rest one's case on an individual published paper (or three or four, ot thirty or forty) and say "because of those the truth is found." But I am looking for cumulative effects of eukaryote LGT. There are not 30 or 40 papers about that for eukaryotes. If 40 papers all make the same mistake, it does not make them true, it just makes them numerous.

    I am trying to figure out what happens in nature, not just trying to publish the next paper. In nature, if the stuff you are saying is true, then you need to see cumulative effects (am I predicting the title of a future paper?).

    I do not expect you to say you wre wrong, too many careers are dependent on the eukaryote LGT story being true. And I really don't care very much at all what you think, I am concerned with the written record as it appears in the library. So folks will find ways to keep eukaryote LGT true enough to keep publishing and getting grants and stuff. Fine. But like I said in my paper, if eukaryote LGT is real (as in actually occurring in noature for the last 2 billion years), then it needs to produce cumulative effects like sequence divergence (generally) and pangenomes (in prokaryotes) do.

    That is not a case of shifted goalposts, because the old ones are still cemented in place and intact (see above). It is a new set of goalposts in addition, at the other end of the field.

    On the positive side, the future for eukaryote LGT remains bright. We see examples from modern politics and science that you don't either to be right or even to represent a majority in order to attain position of influence.

    Taxpayers can expect us to get it as right as it gets in our day and age. So start writing that chapter for somebody's genetics textbook about adaptive eukaryote lateral genetics (without using the term Lamarck).

    Lateral particularism. Now there is a good title.

    So, there it is, this is my entire blogwork for this year. That should give you and your group enough to talk about for the next 24 months, I reckon.

    Yours sincerely,


    1. @Bill

      I will only address the points that are directly relevant to the science here and will not discuss your apocalyptic sociology of science musings and ridicule of eukaryote LGT advocates.

      1) Regarding Drosophila genomes. Your statement implying Yoshida et al. (2017) claimed “0.5% of LGTs per Drosophila genome” is a misrepresentation of that paper. The authors used a method to flag potential LGTs in a given genome of interest that deliberately excluded genomes from sister taxa (in this case arthropods and nematodes). So many of the flagged genes in each genome have orthologs in the other genomes. Yoshida et al. (2017) never stated or implied that these LGTs were specific to each genome. Readers can verify this for themselves (see Yoshida et al. 2017)

      2) Regarding my comment about ‘shifting goalposts’. My comment was in reference to whether or not examples of bona fide eukaryote LGT cases count as evidence against your general claims. In Ku and Martin (2016) BMC Biol. 14:89, the following statement is made: “Our analyses indicate that eukaryotes do not acquire genes through continual LGT like prokaryotes do.” That is a categorical statement…it is different from saying “eukaryotes rarely acquire genes through continual LGT”. But in your Bioessays paper and Ku et al. (2015) you do admit that eukaryote LGT does sometimes occur. It is difficult to mount a case for eukaryote LGT by pointing out clear indisputable examples when there has been no clear statement of what would constitute an acceptable amount of ‘cumulative effects’ of eukaryote LGT to satisfy you.

      3) I completely agree that you have consistently argued since 1998 that genes encoding enzymes of anaerobic metabolism that occur in mitochondrion-related organelles originated in eukaryotes from the genome of the mitochondrial endosymbiont. I have not suggested otherwise.

      4) The main argument against cumulative effects of LGT in eukaryotes comes from interpretations of the analyses of Ku et al. (2015). Here is a direct quote from that paper that is discussing ~1000 genes of prokaryotic origin that appear to be unique to the eukaryotic supergroup Archaeplastida (i.e. apparent lineage-specific acquisitions = cumulative effects):

      “Did Archaeplastida acquire ~68% of their lineage-specific EPCs from hundreds of independent non-cyanobacterial donors? That is what the trees imply, while the gene distributions suggest two episodic acquisitions, each at the origin of plastids and mitochondria.”

      In other words, if we dismiss out of hand the phylogenies of ~680 proteins each of which is suggestive of LGT, then we see no ‘cumulative effects’ of LGT. Are there artefacts that cause incorrect topological inference in phylogenies? Yes of course. But if this many phylogenies are not to be trusted, then why do Ku et al. (2015) even bother to make them? Why bother taking seriously phylogenetic evidence for endosymbiotic organelle origins? Invoking phylogenetic artefacts without providing evidence of a specific problem, or invoking LGTs in prokaryotes erasing evidence of ancestry is a bit too easy.

      Yoshida et al. (2017) PLoS Biol. 2017 15:e2002266. doi: 10.1371/journal.pbio.2002266

      Ku et al. (2015) Nature 524:427-32. doi: 10.1038/nature14963.

  10. Prof. Roger asks a crucial question: "why is Martin so strongly opposed to the idea of LGT in eukaryotes?" The answer is pretty obvious. As Prof. Martin explained in this blog few days ago, one of the foundations of the "hydrogen hypothesis" is that all genes involved in anaerobic metabolism in eukaryotes come from the ancestral mitochondrial endosymbiont which, in his hypothesis, was a facultative anaerobe. Accepting that eukaryotes can acquire bacterial genes by LGT and, especially, genes involved in anaerobic metabolism, is bad news for the whole hypothesis. As examples of LGT in eukaryotic anaerobes have accumulated in recent years, Prof. Martin has engaged in a very aggressive propaganda against any form of non-mitochondrial-or-plastidial LGT in eukaryotes. Qualifying those LGTs of "Lamarckian" is absurd; they follow exactly the same (Darwinian) rules as LGTs in prokaryotes.

  11. Mechanisms mediating LGT in eukaryotes: