Yes, except most folks who go in for this sort of thing think that A & E were flawless - so they would be - wait for it - perfect for each other.
I’ll see myself out…
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Hi Dennis,
That is absolutely right. As I said in the text accompanying the figure:
I would attribute these to mutations since a bottleneck, or, in some cases, recombination.
My point is that we can quite credibly trace the different haplotypes currently found in individuals back to four ancestral haplotypes.
best wishes,
Richard
Some of your recombination events would require two crossovers in a very short physical space. We would then be left wondering why none of the single crossover events are present in the data set. The single crossover events would have to occur first, and then drift to an appreciable frequency to allow for a reasonable chance of a second crossover event to occur. These haplotypes are not derived from four ancestral types. If they were, why do we not see the single recombinant classes in the data? A far more parsimonious explanation is an ancestral haplotype set greater than 4.
Also, have a look at the data set for chromosome 21 in that paper I posted. How are you going to get that diversity down to 4 starting sets? Your model predicts you should be able to do this for the entire genome.
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As a fly on the wall from time to time, thanks for the interesting discussion. Recently it seems to have lost some of its interesting character. This is an aside to the main content of the debate but I do think a clarification is warranted. In his prefatory remarks to this discussion Dennis also says:
…and a reply to Dr. Buggs was clearly not going to be a note that I could dash off in a spare few minutes. And so I left the email unanswered – sorry Richard, if I may call you that – and after a while I forgot about it. Not surprisingly, and completely understandably, Dr. Buggs assumed I wasn’t going to respond, and posted the email on his webpage as an open letter.
One can understand forgetting and certainly can understand not being able to dash off a five minute explanation on a detailed subject. And I’m sure the apology is appreciated. However, as someone who knows both Dennis and Richard, Richard made me aware of his note to Dennis, since there was no reply, shortly after the original note was sent. I would ask Richard if he ever heard from you Dennis, and upon hearing not, reminded you on at least three distinct occasions over the 4+ months passing Richard’s correspondence, asking if you were going to reply. Thus it is important to note that Richard had attempted to discourse privately at first. And there was no need for Richard to have assumed anything regarding your future intentions to respond or not. There simply wasn’t a response - with ample opportunity to provide at least something. So in that context he went public to stimulate a discussion - “before mounting a public critique” as you put it. And as far as I can see, he has well demonstrated familiarity with the literature, whether one agrees with certain ideas put forward or not.
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Hi Paul - welcome to BioLogos. Nice to have friends I know in real life on here as well.
Yes, I was remiss in not replying to Richard, despite your reminders. I think I would have eventually got around to something of a reply - at least I hope so - even if Richard hadn’t posted his letter as an open letter. I do get a fair number of “you’re wrong” - type emails, though not usually from other biologists.
I was correct in that it would not be a quick reply, though! Here we are already several thousand words in already, and more to come… hopefully the fact that the conversation is in the public domain will be useful to some.
Thanks for the welcome, Dennis. And yes - it is not a short discussion! I hope it will be useful as well.
Hi Dennis, I am teaching an intensive postgraduate module over the current fortnight so my responses are going to be slower than they were previously, sorry. Which of the variant positions are you suggesting are double recombinants? Why don’t you think a mutation or gene conversion would be more parsimonious for these?
Let’s keep our focus on this dataset for now. As well as being interesting and a nice illustration that our readers can follow, it is also critical in answering the question of whether the Zhao et al paper supports your case or not.
By the way, I thought of you all as I passed this pub in Westminster yesterday. Dennis, is you’re ever in London, we should meet here for a pint!
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I believe one can trace everything back anywhere from thousands of haplotypes, to a couple dozen, to six, four, two or even a single ancestral haplotype if one is willing to extend the possible lineages far enough backwards in time. For the time spans involved it doesn’t seem credible on the basis of characterized mechanisms we observe today.
Dennis Venema is correct when he notes that the notion of a bottleneck of two individuals wasn’t discarded out of hand or left untested. It appears the analyses simply don’t support it. I wonder if archaeological results could even support it.
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Archaeological evidence shows human populations well above 2, 10 or even 100 for thousands and thousands of years … well past the time horizon of Adam & Eve 6000 years ago.
Who do you think built that buried open air temple in Anatolia 10,000 years ago?
[quote=“RichardBuggs, post:143, topic:37039”]
I think it is fairly clear to the eye that the data present can be divided fairly easily into four groups, that could correspond to small variations on four ancestral haplotypes.[/quote]
I’m another non-specialist with some questions. I’m curious what the data would say about the Y chromosome. Would you suggest that there the data would be explainable as a single group? And in the case of the X chromosome, it would divide fairly easily into three groups (one from the male and two from the female at the bottleneck)?
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My measly BS in Zoology didn’t include much in the way of population genetics, but here is my summary of this discussion using an analogy.
A bunch of scientists are trying to estimate the average weight of a population of elephants. They come up with three different and independent methods of estimating their weight, such as dropping them from airplanes and measuring their terminal velocity, or measuring the weight of water they displace from a tank. They tally their data and find that Method A gives an estimate of 10,500 lbs, Method B gives an estimate of 12,300 lbs., and Method C gives and estimate of 9,600 lbs.
Along comes a scientist who claims that maybe elephants only weigh 2 lbs. He won’t say why he thinks that, or even what evidence leads him to suggest such a thing. This skeptical scientist also states that the methods the scientists used couldn’t detect a 2 lb elephant, but doesn’t explain why. He even claims that a 2 lb elephant would look identical to a 12,000 lb elephant, but also doesn’t explain why this is or back it up with any data.
So we are left with a very, very large group of scientists who have 3 independent methods that all give answers that are close to one another and a single scientist who claims all the other scientists are wrong by a factor of 1,000 for apparently no justifiable reason. Does that seem like it is even a debate?
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Hi Steve @glipsnort thanks for re-joining the discussion. I hope you had a good holiday.
Sorry, my bad. That drop makes perfect sense.
In your original model it seemed that the ancestral frequencies were contributing very little at all to the allele frequencies predicted by the model in the present day, and this is why I assumed that many of them were drifting to zero. Population structure could prevent this drift to zero from happening due to differential fixation of alleles in sub-populations, which could then be supplied back into larger populations when the sub-populations meet again. As for granularity, I was not suggesting a simple or constant sub-structuring of the population. As I said in my original response to your model[quote=“RichardBuggs, post:53, topic:37039”]
I am saying that Steve’s model (at least in its current preliminary form) is making the approximation that there is one single interbreeding population that has been present in Africa throughout history, and that mating is random within that population. However, the actual history is almost certainly very different to this. The population would have been divided into smaller tribal groups which mainly bred within themselves. Within these small populations, some new mutations would have spread to all individuals and reached an allele frequency of 100%. In other tribes these mutations would not have happened at all. Thus if you treated them all as a large population, you would see an allele frequency spectrum that would depend on how many individuals you sampled from each tribe. It is more complicated than this because every-so-often tribes would meet each other after a long time of separation and interbreed, or one tribe would take over another tribe and subsume it within itself. Such a complex history, over tens or hundreds of thousands of years would be impossible to reconstruct accurately, but would distort the allele frequency spectrum away from what we would expect from a single population with random mating. It gets even more complicated if we start also including monogamy, or polygamy.
[/quote]
On reflection, as I have stated above, I would also extend this argument to the ancestral variants. You have argued convincingly that if we simply divide the population into 10 sub-populations and these do not meet or interbreed, then we cannot fit the data. However I am suggesting that reality is far more complex than this, and a long history of sub-division, re-meeting, conquest, occasional migrants etc would tend to result in a smooth curve of allele frequencies, rather than granularity.
Also, I mentioned earlier the issue of mating system. Do you have separate sexes in the model, or hermaphrodites? If the latter, could they self-fertilise? If you did have separate sexes and life-long sexual partners, how would that affect the allele frequencies?
Asking this question reminds me of another question I was meaning to ask: how did you determine the ancestral state of the alleles?
Thank you, that is very interesting. I am glad to see it has a closer fit to the actual data. I wonder if a complex population structure and some admixture from out of Africa could improve the fit further.
Just a thought: what if you parameterised the ancestral population with the genetic diversity found in present day chimpanzees?
To return to the issue of admixture from our of Africa you previously said[quote=“glipsnort, post:67, topic:37039”]
In general, a fragmented population (inside or outside Africa) creates two classes of parts of the genome: those with genetic ancestry entirely within one population, and those with ancestry from a second population. The former will have coalescence times (and therefore diversities) characteristic of the population of the single population, while the latter will have longer coalescence times and higher diversities; their most recent common ancestor has to lie before the time the populations diverged, or at least far enough back for earlier migration to have carried the lineage into the second population. This signature – many regions with low diversity, some with much higher diversity – is also the signature of a bottleneck, in which some regions have variation that made it through the bottleneck and some don’t.
[/quote]
But how would this be distinguishable in an allele frequency spectrum?
I sympathise - this is taking far longer than I had expected also. One issue we have is that as your model is not published, there are still various details of it that we as readers are unclear about (hence my questions above). Would you consider writing this up as a publication, so that everything can be clearly laid out? Or would you be willing to share the code of your model so others can examine it and perhaps play with more scenarios?
Perhaps so, but it is a fascinating issue and one on which is raised (and I fear is the subject of unsubstantiated claims) in “Adam and the Genome”
Could I push you a little on this, please, as it seems quite a faint denial. Are you as certain that a bottleneck of two has not happened as you are that the earth rotates around the sun? Which of the arguments that Dennis makes in the chapter three of “Adam and the Genome” do you find convincing?
Once again, I really appreciate the time you are putting into this discussion, and the expertise that you bring.
Could I ask if there is any evidence which would suggest these ought not to be in the same category of certainty?
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Other than your religious beliefs, what makes you doubt the overwhelming consensus among population geneticists that historic human populations have not dipped down to 2 people in the last several hundred thousand years?
From what I have seen, you haven’t been able to point to a single peer reviewed paper that puts any of these conclusions in doubt. Dennis Venema has even cited papers that specifically test the hypothesis of a 2 person bottleneck in historic human populations and the data strongly rejected that hypothesis:
“Genetic variation at most loci examined in human populations indicates that the (effective) population size has been approximately 10(4) (i.e., 10,000) for the past 1 Myr and that individuals have been genetically united rather tightly. Also suggested is that the population size has never dropped to a few individuals, even in a single generation. These impose important requirements for the hypotheses for the origin of modern humans: a relatively large population size and frequent migration if populations were geographically subdivided. Any hypothesis that assumes a small number of founding individuals throughout the late Pleistocene can be rejected.”
What scientific evidence do you find so convincing that it makes you doubt these conclusions?
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Someone stop me if I’m wrong (@glipsnort @T_aquaticus ), but this is starting to look like special pleading. If we need to posit the existence of self-fertilizing hermaphrodites for which we have no actual evidence, in order to have a chance at getting the bottleneck down to an original pair, it seems we’re drifting well into the zone of apologetics, and further away from actual science.
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I think it may be the exact opposite of what you are suggesting. Buggs is making sure that glipsnort’s model is using diploid dioecious (i.e. separate sexes) organisms. On the flip side, I don’t know if that really matters that much unless we are focusing on the y chromosome.
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Since glipsnort was modeling a human population, this question still makes no sense to me.
@glipsnort - I hope that everything is going as well for you in New England as it is for the Patriots.
If you could post your code to Github along with a very brief readme of which parameters were used for which posts, I can promise that you will see at least one download. I have recently been studying how to run MCMC simulations in Python, and I would love to see how a master of the craft does it in R.
A Github post would have the additional benefit of allowing those who want further info about your simulations to get it self-service by studying your code. The alternative, as we have seen, is that you do the work of addressing ad-hoc concerns yourself–and that does not seem like a fair or viable solution.
Best,
Chris Falter
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