Horizontal gene transfer into humans? I am not convinced. Full text of my comments to reporters here

Some news stories about a new paper claiming evidence for horizontal gene transfer into humans and other chordates. I got asked by many reporters about it and some used some of my email comments in their articles.

See for example

 Here is the full text of my responses:

“got asked by another reporter to comment on this

so – have seen the paper 

it is interesting .. but I am not overwhelmed by what they present in the paper itself. For example, the HAS story seems really incomplete as presented (e.g., the Figure showing the tree does not have all the HAS1, HAS2, HAS3 genes even though they imply they studied that). “

I have been looking through the supplemental information. I find it impossible to judge the quality of this paper without being able to see the alignments they used for each phylogenetic tree. I cannot find alignments for the trees even after going to their Figshare site with the trees. I therefore think there is not much to say about the paper until being able to see those. 

Without seeing the alignments I offer multiple alternative hypothesis for their findings

  1. They have identified genes for which they are unable to produce reasonable alingnments. Alignments are central to phylogenetic analysis and if their alignments are poor quality then the trees will show all sorts of anomalies that have nothing to do with phylogenetic history. By scanning through 1000s of genes and flagging those with unusual patterns they may be selectively identifying genes for which producing good alignments between species is tough. I note – clustalw is a bit notorious for not producing idea alignments in some cases.
  2. I do not buy their arguments for why gene loss is not a possible explanation. They need to present more detail on how many gene losses would be required for each gene family under consideration and then present some evidence for why that # of gene losses is less likely than HGT.
  3. They have not even considered as far as I can tell, the possibility of divergent evolution (as opposed to gene loss) in many taxa which could lead to them being unable to identify homologs in some species
  4. I am not convinced by the arguments against long branch attraction as an explanation for some of the tree patterns.
  5. Related to alignments they need to show which regions of alignments they excluded from phylo
  6. Convergent evolution could also explain some of the patterns they observe.
  7. I could go on. I am NOT saying that HGT into chordates is impossible. It seems plausible. But it is up to them to exclude other MORE plausible alternatives and I just do not think they have done that.

Reporter: asking if it was OK to quote me

Yes it is OK to quote from me. I would like to reiterate – I am not saying they are wrong. Just that I would like to see (1) all the data (e.g., alignments) that unreels their conclusions and (2) them do more to exclude other possibilities.

Reporter asking what other analyses could they do

So – I don’t want to be difficult, but it is their job to figure out how to do such tests before claiming they have strong evidence for HGT. 

In general, this is pretty typical of claims of HGT. Many researchers show evidence that is consistent with the occurence of HGT (which they did here) but few actually explicitly test alternative hypotheses such as gene loss, bad alignments, convergence, divergence, contamination, random noise, and more. I think their work is certainly interesting, but they just have not tested all of these alternatives. And I personally have grown a bit tired of pointing out how people can do better controls for their papers.

Reporter asking about initial impressions:

I see little here that is particularly convincing evidence for HGT …

My follow up email

Note – I am not saying that this is a bad paper — just that I am not overwhelmed by their evidence and especially by what they put in the paper. 

For example, the HAS1 gene story seems incomplete.  Figure 3 seems to show just HAS1 but in the text the say they show the same thing for all HAS genes.  And the tree they show shows a tiny subset of all the available sequences (e.g., HAS1 HAS2 HAS3 and fungal and bacterial homologs).  They claim that they now have proof that HAS1 was transferred near the base of chordates but I just don’t see how they tested alternative hypotheses …

Some related links:

Also here are some presentations from many years ago with some discussion of HGT

Ugg – story about gene transfer/evolution based on NSF press release has a NASA-esque smell

Well, this made me cringe many many times: Extreme Algae Thieves Its Genes From Bacteria – Science News – redOrbit: Science

The article discusses a new paper which itself sounds potentially interesting.  The paper itself sounds somewhat interesting.  But that is besides the point.  The parts that made me cringe are the inaccurate or overhyped statements about the novelty of this work.  Here are some of the statements I find troubling

  • While the ability to pilfer genes from another microorganism has been seen before, scientists have never observed this ability in a eukaryote – an organism with a nucleus.”  
    • Wow.  Completely ludicrous.  There are hundreds if not thousands of papers on lateral gene transfer to organisms with nuclei.  
  • “The results give us new insights into evolution,” said co-author Gerald Schoenknecht of Oklahoma State University’s Department of Botany. “Before this, there was not much indication that eukaryotes acquire genes from bacteria.”
    • Same complaint as above. 
  • “The age of comparative genome sequencing began only slightly more than a decade ago, and revealed a new mechanism of evolution – horizontal gene transfer – that would not have been discovered any other way,” said co-author Matt Kane, program director in the National Science Foundation’s (NSF) Division of Environmental Biology. “This finding extends our understanding of the role that this mechanism plays in evolution to eukaryotic microorganisms.”
    • This quote is deeply troubling.  Genome sequencing did not reveal a new mechanism of evolution.  And it is thus also inaccurate to say ‘it would not have been discovered any other way“.  Lateral gene transfer was studies for many many many years before the first genome sequence was determined.  Certainly, comparative genome analysis helped reveal the extent of gene transfer but it is seriously inaccurate to say it “revealed a new mechanism of evolution“.  Here for example is a link to a google search for the specific phrase “lateral gene transfer” in papers published prior to 1995.  And here is one for the phrase “horizontal gene transfer“. 
    • I hoped that this was a misquote because the person quoted is Matt Kane – an NSF program officer responsible for many areas related to microbial studies.  But alas I found the press release from NSF with the same quote.  Perhaps NSF PR people misquoted Matt.  I hope they misquoted Matt.  Because if not – the quote grossly oversells genome sequencing and what has been learned from it and rather than standing on the shoulders of giants it makes the giants of the past seem like ants.  
  • “It’s usually assumed that organisms with a nucleus cannot copy genes from different species–that’s why eukaryotes depend on sex to recombine their genomes. “How has Galdieria managed to overcome this limitation? It’s an exciting question. What Galdieria did is “a dream come true for biotechnology,” says Weber.”
    • This is wrong in so so many ways.  Again, as discussed above, eukaryotes have been known to undergo gene transfer for many years.  
    • And to say that the inability to acquire genes by LGT is why eukaryotes depend on sex to recombine their genes?  Really?  Uggh.  As far as I know there are no major theories out there that suggest sex is there because eukaryotes cannot undergo lateral transfer (although certainly some theories on the origin and maintenance of sex do indeed relate to increasing diversity by recombination).
    • And what makes this a dream come true for Biotech exactly? 
    • I note – this too was in the NSF press release.  Has NSF suddenly decided to become like NASA in terms of ludicrous PRs? 
I note – I do worry about the effect of calling out NSF on this in terms of my ability to get grants from them.  But this is just terrible stuff in this PR and story and it needs to be stopped.  I note further that I consider Matt Kane a friend and I hope that he clarifies his quote here and also manages to get NSF to be more rigorous in their PRs.