Author: Jonathan Eisen

Just reading this paper and thought I would start a new “section” here on my blog.  Journal club light.  Just some notes and quick comments.

Today I am selecting this paper: Phylo SI: a new genome-wide approach for prokaryotic phylogeny.  It caught my eye because, well, I am interested in genome-wide phylogeny.

So I glanced at the paper’s abstract:

The evolutionary history of all life forms is usually represented as a vertical tree-like process. In prokaryotes, however, the vertical signal is partly obscured by the massive influence of horizontal gene transfer (HGT). The HGT creates widespread discordance between evolutionary histories of different genes as genomes become mosaics of gene histories. Thus, the Tree of Life (TOL) has been questioned as an appropriate representation of the evolution of prokaryotes. Nevertheless a common hypothesis is that prokaryotic evolution is primarily tree-like, and a routine effort is made to place new isolates in their appropriate location in the TOL. Moreover, it appears desirable to exploit non–tree-like evolutionary processes for the task of microbial classification. In this work, we present a novel technique that builds on the straightforward observation that gene order conservation (‘synteny’) decreases in time as a result of gene mobility. This is particularly true in prokaryotes, mainly due to HGT. Using a ‘synteny index’ (SI) that measures the average synteny between a pair of genomes, we developed the phylogenetic reconstruction tool ‘Phylo SI’. Phylo SI offers several attractive properties such as easy bootstrapping, high sensitivity in cases where phylogenetic signal is weak and computational efficiency. Phylo SI was tested both on simulated data and on two bacterial data sets and compared with two well-established phylogenetic methods. Phylo SI is particularly efficient on short evolutionary distances where synteny footprints remain detectable, whereas the nucleotide substitution signal is too weak for reliable sequence-based phylogenetic reconstruction. The method is publicly available at http://research.haifa.ac.il/ssagi/software/PhyloSI.zip.

And something continued to catch my eye there.  It was the use of “gene order conservation” as the data for the phylogenetic analysis.  Hmm.  I am generally skeptical of most uses of gene order for inferring phylogeny that I have seen.  Why?  Well, because it seems to me that gene order is less likely to be a useful character than sequences in alignments (which is the standard for inferring phylogeny).  Why do I feel this way?  Well, for two main reasons:

1) Sequence alignments are robust.  They have been used and used and used and shown to be quite powerful and useful (even though they are not perfect).  The rich literature on alignments has shown where and when and how they are useful.  And where and when and how they are not.  And we have powerful, tested methods to use such alignments.

2) Gene order seems less likely to be robust.  I am not saying it is not useful.  But the literature I have seen suggests to me that gene order is more prone to convergent evolution than sequence.  And gene order is more prone to enormous variation in rates and patterns of evolution.  And gene order does not actually have a lot of characters to use compared to whole genome alignment based phylogenetics.

I could go on and on.  There are many other reasons I prefer sequence alignments over gene order.  But I am willing to consider that gene order could be more useful than I imagine.  So I read on.  And the first thing I did (which is almost always the first thing I do for new phylogenetic methods papers) was I looked at their phylogenetic results.  And so off to Figure 9. And the results did little to convince me that their method was better than existing alignment based methods.

I am sure people cannot see this that well.  But basically, I looked through the tree and there were just too many things that are inconsistent with trees that are very supported by lots of other data.

For example

which has in one clade species that almost certainly should not group together.  In particular the presence of Neisseria in this group is very strange given that all other analysis put it in the Protebacteria and the Proteobacteria are found in other parts of the tree.

And there is another clade like this

With Francisella (also considered a Proteobacteria) in a clade with things from many other Phyla.

And then there is this one.

Which has gamma Proteobactera, alpha Proteobacteria, Spirochetes, and others all together in one clade.

I could go on.  But this is journal club light.  I just do not have time right now to dig much deeper.  But on first look, I am certainly not overwhelmed with a desire to use gene order instead of sequence alignments to infer phylogenetic trees for bacteria.  Again, I am not saying the method does not have its uses.  It easily could be useful in many ways.  But for inferring trees of all bacteria at once – does not seem to be the right thing.