I have some interest in the field of anthropology and evolution but my knowledge in these fields is rather limited. Just recently I got involved in the discussion about the origins of modern humans and Neanderthals. I have read some seminal papers in the field as Krings et al., 1997, Krings et al., 1999, Ovchinnikov et al., 2000 to get some arguments but I had some difficulties in data interpretation in these articles.
My opponent says that if human and neanderthal sequences differ in around 35 positions and human (and diverge at 500 000 ya) and chimpanzee in around 60 postions (Krings, 1997 gave 55, Krings 1999, gave 93) then if we take the substitution rate the same for these comparisons (because human/chimpanzee divergence served as calibration point) the time for human/chimpanzee divergence will be in the range of 1,5 million years, which is senseless. I know that something is wrong in this logic, because Krings, 1999 gave the neanderthal/chimp difference as 94 bp. But I cannot reproduce simple and understandable way of calculation of species divergence age. I think that not all information was presented in papers because it is regarded as a basics for evolutionary biology. I have rather poor background in the field of evolution rates quantitation.
Can you, please, help me to produce the understandable and simple interpretation of the data in the papers, i.e. how to convert the differences in the sequences to the evolutionary divergence age for human/human/, neanderthal/human, human/chimp, neanderthal/chimp? I tried myself the simple quantification based on Krings, 1999 (substitution rate - 0.94x10-7 per site per year per lineage) paper but I got quite strange results that do not correlate to the paper, so I presume that I did not understand methodology:
Humans/chimps = 2,9 mln ya
Neanderthals/chimps = 2,94 mln ya
Hum/Hum = 344 000 ya
Hum/Neand = 1 mln ya
I will be very grateful for any hints or help because this situation drives me crazy.
I tried myself the simple quantification based on Krings, 1999 (substitution rate - 0.94x10-7 per site per year per lineage) paper but I got quite strange results that do not correlate to the paper, so I presume that I did not understand methodology:
Krings et al 1999 (in PNAS Vol. 96, Issue 10, pp 5581-5585, May 11, 1999) cite the following paper for their mathematical methods:
The paper is on-line at Professor Nei's own pages. He has a heap of publications in this area, and many are available there. Unfortunately there are some bad links. I’ve given a link to the paper in question that seems to work. You may need to replace "Nei" with "Nei/Lab" in some URLs.
The maths in this paper is very detailed; I won't try to summarize here.
Examining the pattern of nucleotide substitution for the control region of mitochondrial DNA ( mtDNA ) in humans and chimpanzees, we developed a new mathematical method for estimating the number of transitional and transversional substitutions per site, as well as the total number of nucleotide substitutions. In this method, excess transitions, unequal nucleotide frequencies, and variation of substitution rate among different sites are all taken into account. Application of this method to human and chimpanzee data suggested that the transition / transversion ratio for the entire control region was ~15 and nearly the same for the two species. The 95% confidence interval of the age of the common ancestral mtDNA was estimated to be 80,000-480,000 years in humans and 0.57-2.72 Myr in common chimpanzees.
Hope this helps.
Cheers -- Sylas
Added in edit: link and cite for Krings et al 1999
This message has been edited by Sylas, 12-19-2004 10:06 PM
Also, I would check the sampling size, and compare that with the range existing within the present human population. I would especially consider situations with more of one tribe breeding, more of an in-bred situation, and you are likely to see similar independent and unique features in that group of humans as well.
Actually, most studies IIRC show that Neanderthal features usually fall outside the range of modern humans. In my page here (http://redrival.com/evolusi/humevol5.htm) I showed that the brain volume/body mass ratio of Neanderthals is lower than the H. sapiens ratio, also their semicircular canal curavture (Hublin et al. 1996, Nature 381: 224--226) fall outside the range of modern H. sapiens.
And of course Neanderthals are humans. Australopiths are also humans IMO.
I don't have time to follow the math through in detail so I can't be certain, but I believe there is no simple way to extract the age estimates. The problem is that the mutation rates in mtDNA vary a lot from site to site. At the average mutation rate, you don't have to worry much about the same site mutating multiple times over a few million years, but in reality, with the rate varying so much, some sites will mutate repeatedly. Therefore the divergence between the mtDNA of two species does not increase linearly with time; instead, it increases more and more slowly as mutation saturates the more mutable sites.
If I have understood the background papers correctly from skimming through them, they're modeling the distribution in mutation rates as a gamma distribution with a shape parameter of 0.11. This is a highly skewed distribution, with high probability of low values and a long tail of high values. I.e. most mtDNA sites mutate pretty slowly, but there is a wide spread of mutation rates out to very high values. This is certainly consistent with what I know about mtDNA mutation rates. So you really have to use a fairly sophisticated model to extract an age estimate under these conditions.
(There's another effect you have to worry about here too, which makes it wrong to simply take the ratio of Neandertal/human divergence to human/human divergence. The problem is that population ancestral to humans and Neandertals had some mtDNA variation in it (comparable to the levels seen in modern humans, perhaps), and some of this variants went into the Neandertal line and some into the modern human line. To correct for this you have to know the effective population size of the ancestral population, but I don't think this is a large contributor to the problem here.)