Beyond Reasonable Doubt? A Test for Common Ancestry


(Paul A Nelson) #16

OK, thanks. I’ll see if I can find him and obtain the data.


(Paul A Nelson) #17

Here’s why I am worried about the alignments (Bojian Zhong is senior author on this paper):

Notice that the phylogenetic signal from chloroplast sequences was “improved” by editing out GC sites which caused problems with a monophyletic hypothesis.

Such practices are widespread in molecular phylogenetics. These methods rarely elicit critical comment because monophyly is taken as given. One should only use “phylogenetically informative” sites in constructing evolutionary trees.

I should be able to reach Zhong by email later today or tomorrow (traveling right now, but will have some time tomorrow).


(Bill Cole) #18

The test in the paper seems to be independent of a transitional mechanism. Is this the case?


(Blogging Graduate Student) #19

Yes, the test has nothing to do with mechanisms of “transitions”, it’s just a test of CA versus SA. The “what”, not the “how”.


(Bill Cole) #20

I then agree with Joshua that the prokaryotic to eukaryotic transition is not a good example based on the papers test method as so many new proteins were added during this transition. Comparing homologous proteins does not explain much.

This does limit the subject to common descent vs universal common descent.


(Blogging Graduate Student) #21

To be clear, they didn’t didn’t edit out GC sites that “caused problem with a monophyletic hypothesis”, they edited out GC sites that were contributing to the unresolved nature of classifications with Chlorophyta. The phylogeny of the classes within Chlorophyta (as well as the monophyly of some of these classes) was thus far unresolved, giving conflicting results and weak support in different studies. Fang et al set out to resolve these conflicts - to find the real phylogeny, regardless of what it was. There’s nothing to suggest that the authors were cherry-picking sites to remove in order to support a particular phylogeny, as you seem to be suggesting.

Their reasoning holds up - if GC heterogenous sites are known to be rapidly-evolving and lacking any useful phylogenetic signal, it stands to reason that they be removed, reducing the noise in the rest of the analysis.

Are you suggesting that these phylogenetically “uninformative” sites are actually some kind of signature of seperate ancestry? Can you elaborate on that?


(Blogging Graduate Student) #22

As I said in the OP, strictly speaking this isn’t about universal common descent because it’s not including all groups of organisms, but it is including a great many groups that creationists/IDers should be concerned with.

Edit: actually I noticed that I didn’t include the line about this not being strictly about universal common ancestry in the OP (I must have deleted it in the final draft), so apologies if that wasn’t clear.


(S. Joshua Swamidass) #25

That would be really helpful @pnelson. Thanks.

I’ve been thinking about this study, and have some questions about it. It is not clear they have done the right controls.

@evograd, honestly, I’m not sure this is a valid test. And this is coming from a scientist that affirms common descent. I am no anti-evolutionist. I could be wrong, but it seems it is fairly easy to build a generative model that would show evidence of common descent according to this test. Here is how we could do it.

  1. Define a relatively large convex space in sequence space as “functional” (e.g. a fixed set of differences from a centroid sequence).
  2. Sample sequences uniformly from this functional space to assign sequences to different species.

There is no reason to think it must be a convex space. I’m just saying that here to make it easy to visualize. I’m pretty sure the same finding would apply for any shaped space, as long as it is large enough.

Now, look at the basic intuition here:

the expectation that, under evolution, the ancestral sequence of one natural group of taxa will be more similar to the ancestral sequence of a second natural group of taxa, than to any sequence from the first group will be to any sequence from the second.

Now, in this generative model, which does not include common descent, the same prediction is made. The ancestral sequence will be approximately the “average” of all the sequences in the taxa, and will statistically be much closer to the centroid sequence. So the ancestral sequences will always be closer to one another than the extant sequences are to one another.

Unless I am missing something, it appears that this is a flawed test. Did I miss anything @evograd? What do you think @pnelson?


(S. Joshua Swamidass) #26

I think I disagree. The test’s expectation starts from an understanding of sequence evolution, which is a transitional mechanism. It seems they are presuming largely neutral mutation with negative selection in setting the expectation for common descent.

Once again, @evograd, am I missing something? What do you think @Joel_Duff and @pnelson?


(Blogging Graduate Student) #27

Yes, they’re beginning with assumptions about the stochastic nature of sequence evolution, but at the same time their results in figure 4, whereby ancestral convergence increases with sequence length, acts as a somewhat independent confirmation of this implicit assumption.


(Ashwin S) #28

I am trying to understand exactly what you said… are you referring to how the clades are initially defined? (i.e based on similarity between functionally conserved sequences?)

In that case would the test be more neutral if non conserved sequences are selected.

If i am way off the mark (which is very likely), can you explain in a way a non specialist could understand?


(Blogging Graduate Student) #29

I’m not sure I quite understand what you’re describing. I’ll go with what I understood it to mean for now, but please correct me if I misunderstood.

So if we define a corner of sequence space as “functional”, then if this corner is big enough there will inevitably be a “centroid” sequence that is equidistant from each of the edges of this space. I agree with this part, but the second part seems suspect to me. If we samples sequences in this space uniformly, putting half of the sampled sequences into group 1, and half into group 2, then surely there would be no significant difference between the average distance between sequences in group 1 and 2, and the distance between the inferred ancestral sequences of group 1 and 2?

The only way to the observed pattern would be to sample from 2 different ends of the sequence space, one side for group 1 and 1 side from group 2. This is the point of the test though - the ancestral sequences will more closer than the average extant sequences because each group has neutrally explored different “sides” of the sequence space, and that the sequence space is inherently convex because of common ancestry. If there was no common ancestry, there would be no reason to expect this kind of “divergent angle” in the explored sequence space.

I think is the crux of it - precisely that the ancestral sequence will not be the “average” sequence. If it was, then we’d never expect to see any significant results in their test. Remember, they’re comparing the “average” sequences of each group and comparing the ancestral sequences of each group. If the average sequence and ancestral sequence were basically the same, the test wouldn’t return any significant differences in their comparisons, leading to results that would fit the null model. What the test does is see whether the inferred ancestral sequences are different to the average sequences. If they’re not, the null model would fit the results. If they are, then there are 2 options: either the ancestral sequences converge or diverge, relative to the comparison of the average sequences from each group. I’m not sure what it would mean if the ancestral sequences were more diverged, it might imply that the groups have seperate origins but are converging in the same direction over time, but the implications of the ancestral sequence converging is clear. The groups diverged form an ancestral sequence AKA common ancestry.


(Paul A Nelson) #30

On what basis are the sites “known to be rapidly-evolving” and “lacking any useful phylogenetic signal”? Every site in the sequences has a history. Right? So how do we know which sites represent noise?

I’ll comment further in this thread after I obtain the unaligned and aligned sequences from Zhong (from the PLoS 2013 paper linked by evograd).


(Blogging Graduate Student) #31

Well, in this case, Fang et al. point out:

By contrast, the phylogenetic tree inferred from the removed GC-heterogeneous sites of the gc_168 dataset under the heterogeneous model is poorly supported (supplementary Fig. S13), which indicated that these GC-heterogeneous sites contain noisy signals.


(S. Joshua Swamidass) #32

Because we can directly measure the increased rate of mutation, and see that it corresponds also with increased divergence. That is independent corroborating experimental evidence that they are less phlyogentically informative.


(Ashwin S) #33

This is a valid point and I can see why scientists use it for making phylogenetic trees based on assumptions of common descent.
However, the paper states that it wants to test seperate ancestry of individual species as well as that of CAs in a group as a null hypothesis. In such a case, shouldn’t they refrain from segregating sites in any way? Or is their claim that using “long sequences” would even things out fair?
Also I am really interested in your conversation with @evograd on the paper. Is his understanding of your point correct. Do you accept his argument for the premise of the test?

I request you to respond as and when you have time.

@evograd- I appreciate you pointing out this paper. I think Theobalds paper was a step in the right direction (even though his method was falsified). I am glad to see scientists continue to develop a formal test for common ancestry.


(S. Joshua Swamidass) #34

There is no assumption of common descent in my claim. It is just a valid point, without an assumption of common descent. I’m not engaging in polemics here. This just logic. Do not dismiss what I am saying by assigning assumptions to it that are not there.

I take my scientific claims very seriously. If you think there might be an assumption, you can ask. Please do not assert falsely there is an assumption in order to dismiss it. I understand you may not know the assumptions behind my point, which is why you should ask the question instead.


(Ashwin S) #35

Fair enough.Just to clarify, I was talking about assumptions made in phylogenetic trees. Not assumptions you made…That’s why I asked further questions which would clarify the issue as below.

Edit:@swamidass, pls note that right now I am not trying to make arguments for or against this paper. I am just trying to understand it… Hence the questions…


(S. Joshua Swamidass) #36

I want to be clear here. I affirm evolutionary science including common descent. Also, my thoughts here are provisional. Nonetheless, as I’ve been thinking carefully about this, I do not think this is a valid test of common ancestry. It appears that an obvious special creation model that would produce the exact same results.

Why is this important? We have really strong arguments for common descent. Incorrect arguments, however, do much to cloud truth. We have no need for them. Of course, maybe I missed something and I want to put this out there to be reviewed.

This does not appear to be true. It appears you misread the paper, or miswrote what you correctly read. Let me show you what I mean. Here are the key parts of their methodology…

For Step 1 we take two subgroups of taxa X and Y (see Figure 1) that on independent evidence have non-overlapping subtrees; that is, they are natural subgroups (or clades). …

The program MUSCLE [14] is used for calculating alignment scores, see details later. For Step 5, the pairwise alignment score s(ax,ay) is then calculated between the inferred ancestral sequences ax and ay (we call this the ‘ancestral score’), with higher values showing that ancestral sequences are more similar (Table 1). In Step 6 we then calculate the alignment score s( i , j ) for all pairs of sequences (with just one sequence from each of the two subgroups). From the resulting distribution of between-subgroup scores (see Figure 2) we calculate (Step 7) the probability p of observing scores at least as high as the ancestral score under the null model, which we now describe.

They are NOT comparing the ancestral sequence difference to the average sequence difference (as you say). Rather, they are comparing the ancestral sequence difference to the distribution of inter-group pairwise differences. That is why they show these cumulative distribution plots (see Figure 2):

Given that fact, it remains exactly true what I said in the first place.

What I mean by a “generative model” here, is a non-common descent generative model, based on picking things from a defined space of sequences with a defined protein function.

So good. We agree.

What I am saying is that the “average” is approximately the same (not exactly) as the “ancestral” in this conception. That remains true. You had misunderstood the algorithm. It is comparing the distance between the ancestral/average and the distribution of inter group distances.

Remember, also, that the groups are not uniformly distributed in space. One group is one half of the convex space, the other group is the other half. If the extant sequences are confined this way, with any spread at all, it might even be possible to mathematically prove, that the ancestral sequences must be more similar than the median of the comparison distribution. I don’t have that proof yet, but my instinct tells me that such a proof is actually possible.

Contrast with their claim:

Our test is based on the expectation that, under evolution, the ancestral sequence of one natural group of taxa will be more similar to the ancestral sequence of a second natural group of taxa, than to any sequence from the first group will be to any sequence from the second. In contrast, a variety of proposed non-evolutionary models either do not make this prediction, or require so many parameters that they cannot be said to make any testable predictions at all.

First off all, they are being sloppy here. By that definition of their test, several figures here would seem to invalidate the predictions of common descent (!). Setting aside the sloppy language, notice that they do not even appear to test any of these non-evolutionary models (why not?). I might have missed it, it appears they have no negative controls, and merely make a high level logical argument of the expectations of a non-evolutionary model. This, honestly, seems to be poor methodology.

It is possible I missed something in the paper. I want to be corrected if I am wrong. If I am wrong, there are less consequential tings to work through. This, however, towers over the rest in potentially invalidating the entire study.

What do you think @evograd and @pnelson ?


(S. Joshua Swamidass) #37

Great. These are all small potatoes questions though. I’m concerned about a more fundamental problem, that cannot be easily rectified. If my concern is justified, the test is not valid, and these other points are not important to engage.

In this case there is no assumption being made. They are making a statement that:

  1. We can build two trees of two groups of related sequence. (de facto true, no assumption)
  2. If common descent is true, (that is the claim to be tested)
  3. then there will be a specific mathematical pattern observable in these these two tree. (because it is between the two different trees, no common descent assumed)

No assumption of common descent. It is really critical to carefully understand these things instead of kicking up noise (not saying you are doing that @Ashwin_s). Bad arguments against bad arguments just add to the confusion. We want to get this right. I have no incentive to be dishonest or sloppy here. Quite the opposite.