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.
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.
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.