The only thing I would add is that some of the papers I have directed Richard to, such as the Alu paper and a few others, have not, as of yet, been responded to by Richard. These papers also test Richard’s hypothesis of a bottleneck to two, and reject it.
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Ok, Linkage disequilibrium - here we go. This will probably steal some thunder from my full treatment later, but here’s a sampling.
In a bottleneck to 2 people, four versions of any given chromosome pass through the bottleneck (two in each person). Each chromosome has variants on it in a particular pattern. These four chromosomes are now what are called haplotype blocks - groupings of alleles physically linked together.
After the bottleneck, recombination through chromosome breakage and rejoining (“crossing over”) will be necessary to start mixing and matching the four sets into new patterns. The closer together two variants are, the less likely a crossing over event will occur between them.
The overall, average recombination (crossing over) rate in humans is around 1% per generation for every million base pairs. This rate can and does vary somewhat across the genome, but the variants we are discussing here are really, really close together - 1000 base pairs apart or less. Crossing over between two such alleles is thus really rare.
You can see the region that Richard and I are discussing here if you want to look at the raw data. (You’ll have to play around with the default settings to show all the variants. Click on “tracks” and then “variation” to see the alleles.)
If we were to pack a significant number of alleles into two people, such that the alleles would survive the bottleneck, that would place those alleles into four sets of very tightly linked variants, or haplotype blocks. As the population expands exponentially after the bottleneck - required in order to save as much variation as possible in this scenario - the vast, vast majority of offspring would inherit one of the four blocks without any crossing over. This would continue for generations, with only extremely rare crossing over events eventually breaking up the haplotype blocks.
Once those new, rare, recombinant offspring arise their new haplotype blocks will have to drift up to the intermediate frequencies we see in some cases for such blocks. All of the issues facing drift for individual alleles (as Steve has modelled for us) also apply to new blocks.
The net effect is that the resulting population would be heavily biased towards the starting four haplotype blocks, with all the variants packed together, and there would be fewer haplotype blocks that arose through crossing over.
When we look at this region we don’t see what a bottleneck to four would predict. We don’t see all the variants grouped together into four different haplotype blocks. We see the variants dispersed in different combinations. What we see just doesn’t fit a two-person bottleneck model.
This sort of analysis was done at a massive, genome-wide scale by Tenesa et al, 2007, and they conclude that human population sizes have stayed in the several thousands over the last 200,000 years, as I discuss in the book. This group looks at millions of marker pairs, many of which are much further apart than the ones in this small region of the genome we are discussing here.
No amount of juggling of recombination rates will get these sorts of studies down to 2. To get down to two requires special pleading in the extreme.
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What amazes me in all of this is that even with all the time and effort put into this conversation, there hasn’t been a single acknowledgement from Richard Buggs that he was wrong or even a mere acknowledgement for that matter of the evidence that has been presented to him.
He hasn’t even issued a thank you for all the time that you and Steve have put into answering this.
I’m hoping he doesn’t dig in his heels and prove to be immune to evidence, but I fear he has done just that.
I tend to see things a little differently, as there has been a good mutual exchange of ideas and interpretations. We are then capable of looking at the evidence and making our own judgements regarding their validity. In exchanges like this, we seldom see a situation where positions are changed remarkably, but it does help clarify the issues and provides an opportunity for all involved to express their thoughts to our benefit. My thanks to Dr. Buggs and Dr. Venema for their contributions.
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He certainly has. He has thanked them repeatedly. Here’s an example.
Here’s another example.
Here’s another one.
Two more times in this post.
More thanks here.
Here also.
Richard has been very courteous, grateful, and appreciative. The entire discussion has been complex and difficult, with occasional obvious frustration, but the level of decorum has been extremely high.
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Will there ever be a (Part 2) ?
If there is to be one, it could be something along the lines:
Adam, Eve and Population Genetics: A Reply to the book: “Theistic Evolution: A Scientific, Philosophical, and Theological Critique”
I see that this book is at the bargain cost of $60.00.
I’ve been going through my sofa, trying to pull together the purchase price. I’m up to $3.23, 2 safety pins and three “fun sized” Charleston Chews. I’ll trade the pins, the candy, or both (!) for the remaining $56.77.
Hi all,
I have been away over the weekend visiting my parents with my wife and son, and have just got back to this discussion today. I see that @cwhenderson has made some comments designed as a summary of where things are at. For my part I would briefly say this.
I came into this discussion with two questions in my mind:
- Does chapter three of Adam and the Genome make a convincing case that humans have never passed through a bottleneck of two?
- Is there a better case that can be made?
I came to both of these questions with an open mind. Regarding question (1) I had very serious concerns about Dennis’ chapter, which I expressed to him privately in an email in the spring, and then later made public. I did think that Dennis might be able to defend his chapter well when challenged and come up with missing references. So far, however, I have been disappointed with his defence of his chapter (thought grateful that he has made it), and I have growing certainty that even if his conclusion - that there never was such a bottleneck - is correct, it is correct for the wrong reasons. Regarding question (2) Dennis has cited some papers that were not alluded to in his book, which I still need to read. Given my disappointment in the other citations that Dennis has pointed me to in the past through his chapter and in this discussion, I am not optimistic that any of these will really support his case when examined closely. But I will read them in case they do prove his point. In addition, Steve Schaffner has given some evidence from allele frequency distributions that these make a case against a bottleneck of two. This is an intriguing argument, but I have questions that have not been fully dealt with regarding the role in the model of alleles that are derived from before the bottleneck, and also the effect of population structure. I also note that because Steve has presented this analysis that is not in the peer reviewed literature, it seems probable that he does not find what is already in the peer reviewed literature as convincing as Dennis does. I am also getting less optimistic that there is a strong case to be made against a bottleneck of two because I have not had any responses to my blog at Nature Eco Evo - which was aimed at research scientists and has been read many times - saying that I am clearly wrong and have missed a crucial piece of evidence that shows that a bottleneck of two is effectively disproven. I maintain an open mind on this wider issue however.
The reason why I stopped asking @glipsnort questions was because he was taking some time out over Thanksgiving, and he has not yet responded to the questions I posed just after he left the discussion.[quote=“DennisVenema, post:119, topic:37039”]
The only thing I would add is that some of the papers I have directed Richard to, such as the Alu paper and a few others, have not, as of yet, been responded to by Richard. These papers also test Richard’s hypothesis of a bottleneck to two, and reject it.
[/quote]
I will come on to those papers in due course, Dennis, as we have not yet completed our discussion of Zhao et al 2000, which is the first one of the batch of papers that you directed me to that I have addressed. As we have discussed, the parts of this paper that you highlighted did not test a hypothesis of a bottleneck of two and do not support your certainty against this hypotheses. I think you have agreed with that critique and we are now in the midst of a discussion as to whether or not the final coalescent analysis of the paper is persuasive evidence against a population bottleneck of two.
I have just had a read through the comments that you made about this since I have been away for the weekend. I am glad to see that you have backed away from your claim that 75 variants could not make it through a bottleneck of two, and that you are now talking about how they are arranged in haplotypes over the 10Kb region. That is much more appropriate and to the point. However, you present no analysis of the haplotype structure of the region we are discussing, nor do the authors Zhao et al write about this in any detail. You are quite out on a limb here, making claims about the data that the authors do not make.
Please could you present some analysis of their data and show that there are not four major haplotypes for the higher frequency variants that could have come through a bottleneck? As you know, linkage disequilibrium in the human genome means that very few of the haplotypes that are possible from existing SNVs are present in human populations.
Please note that I have already commented on your use to the Tenesa et al paper in my Nature Eco Evo blog, and I am looking forward to your response to my critique.
I would also note, Dennis, that as well as the outstanding task you have given me of reading though four more papers (which I plan to fulfil), I have also suggested a task for you that I believe remains outstanding:[quote=“RichardBuggs, post:108, topic:37039”]
to explain in your own words (without help from Steve) what Steve was modelling, and how it shows that a bottleneck of two is unlikely to have happened.
[/quote]
I am sure that many of the readers following this discussion would welcome such a summary.
Hi Richard - welcome back to the conversation.
I’ll let @glipsnort comment on his confidence re: the data as we have it, but don’t forget he’s also waiting for evidence of a turtle rather than a duck…
I’m also hoping that eventually you’ll take this on yourself too - you’re a biologist, after all, so this should be possible for you to work on this for yourself. The 1000 genomes data set would be the logical place to start. How about a model that proposes and explains the linkage disequilibrium data coming from just 2 people? I think if you started working on that angle you would quickly see the problems. It’s not without reason that both Steve and I have been asking you to do some modelling for yourself.
Eventually I hope to have a full reply to you done. I’ve given Part 2 to Brad and Jim, and I’m waiting for their feedback. Pending that I’ll draft part 3. I’m also unusually busy this week with a number of events, so, don’t hold your breath…
I also don’t know why you keep saying things like I don’t allude to the papers I’ve cited to you in the book. Do you really think I would write a book for a popular audience and just make a guess at what the data says? Or is it more likely that I would read the evidence at some depth before writing the book?
I’m also surprised that you haven’t already read those papers. If I was in your shoes, I would have familiarized myself with the field as a whole before mounting a public critique.
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I am one of the readers who wants to see the evidence for a bottleneck of two. If I have missed it in all the posts, could you please link to it? Are there any scientists who argue for a bottleneck of two any time in the last 100,000 years?
As I said before, I have only one question for this discussion. Does your understanding of the data support the idea of an Adam and Eve who had no ancestors at all (neither human nor pre-human), as the universal progenitors of every human who has ever lived, with no humans descending from any parallel humans or pre-humans, approximately 6,000 years ago? That’s all that matters to me.
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Richard,
While we’re waiting on Dennis’ reply, I’m hoping you can bring a little more clarity in your main critique with respect to the studies he referenced for you.
For what it’s worth, I can give you my own impression of what may be happening here by way of analogy. Let’s say we have a YEC criticize the available peer-reviewed literature for not testing his “hypothesis” of an ice canopy. While the mainstream scientist may provide you with references till they’re blue in the face on paleoclimatology, physics, cosmology, etc., you continue to object that your particular “hypothesis” of an ice canopy has not been explicitly tested and rejected and so all this bravado from scientists on their confidence of what the earth looked like in the ancient past is faulty. So, as this mainstream scientist just cannot dig up a laser-focused rebuttal to your particular arbitrary model, they simply run calculations for you demonstrating the implausibility of your claim. Which you then take to be a weakness of the existing literature. Why run the numbers if the available studies already refute it you say?
I think (or hope) we can all see the absurdity of such an approach. And while I’m getting the sense that this MAY be what is happening here with your critique on Dennis, I don’t know it. So I’m hoping you can clear this up for me. What are your main issues with how he is or is not engaging the available literature? As succinctly and clearly as you can sum them up? I look forward to your thoughts.
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Agreed, I haven’t even seen anything like this at AIG or ICR. Granted, I don’t read exhaustively at either site, but such a claim would’ve likely caught my attention.
Organizations like AIG and ICR have made a kind of hamfisted attempt to do this with lots of fuzzy talk about Mitochondrial Eve, and AIG has made its own claim about a genetic bottleneck. This recent genetic bottleneck argument is obviously being promoted by the Discovery Institute. However, CMI is following the current discussion at Biologos.
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In order to “see” what I’m getting at, you would have to look at the 1000 genomes data and assemble the various haplotypes in their sample from the region in question. There are more in the database now, obviously, than when the paper was published. This is part of what I was saying when I said that some of what you are looking for is just familiarity with published data sets.
This region of the genome is not atypical. It has a haplotype structure like other regions, and scrolling through the data yourself is the best way to convince yourself that it could not descend from just two individuals.
If you want to see how this sort of thing looks, here’s a paper (PDF) that does this for a limited data set for the entirety of human chromosome 21. Look at figure 2 - those are 20 individual chromosomes from their sample (African, Asian, Caucasian). Note well that this is an early paper with a limited data set, but there are more than four common haplotypes even in this very limited data set. Note also how closely linked these SNP sites are. The problem for a 2-person bottleneck hypothesis only gets worse as you add in the reams of data we’ve added since.
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@cwhenderson, @Jonathan_Burke : All we have seen from Dr. Buggs is a list of assigned tasks for how @DennisVenema should run the data differently.
There has been zero effort made to run data the way Dr. Buggs says it should be run, so that we can all see for ourselves.
@RichardBuggs, how long before you do a test run … even with hypothetical data?
Richard’s suggestion that all common variation was packed into two founding individuals and then recombined afterwards into the patterns we see today is actually found in the YEC literature. (Yes, I spend too much time on these things - sigh). Robert Carter is an example of a YEC who tries to get around the bottleneck/founding with 2 problem this way. The challenge for YECs (and Richard) is explaining the patterns we see in the present day with reasonable recombination events. There is also the issue of drift to intermediate frequencies, because small haplotype blocks are effectively “alleles” that can increase or decrease in frequency like individual variants. Although I think Carter starts with a population of one, since Eve is a clone of Adam (presumably with a subtracted Y and a doubled X). In this case, you have to deal with only two original chromosomes, not four.
Why would @DennisVenema need to describe separately what @glipsnort was modelling, if Steve himself already explained very clearly what he was modelling? What purpose does that serve, other than “testing” Dennis? It appears to be an unnecessary demand that does not further the conversation.
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I would suggest that this approach would be more consistent with a literal interpretation of Genesis.
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I think this is where AIG goes now too, though I can’t recall exactly.
And it points out the problems with a very literal interpretation. The genetic makeup of Eve. The origin of Eve’s biomass (what does a rib weigh? a pound, depending on which rib?). The genetics of the offspring. The problem of creation of mankind on the 6th day vs Genesis 2 story. To take it as addressing science places you in a strange position if you try to explain it all. I do not mean to sidetrack the conversation, but these issues are what are going on in the background in my mind when these sorts of discussions come up. If further discussion along these lines is desired, we can move to another post to maintain the integrity of this discussion.
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In some ways it is relevant to the conversation… Richard has been asking about a bottleneck to two individuals, but perhaps a bottleneck to one is what really should be discussed here. In that case we’d be down to only two starting chromosomes.
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