How do you calibrate the molecular clock?
How do you calibrate the molecular clock -- where you need a few known sequence divergence times -- when you only know a few speciation times?
Yesterday at a meeting (I'm not sure I can tell you which meeting; I'm not sure how open it is supposed to be :-/) we discussed the divergence time of human-orangutan and human-macaque. We need the sequence divergence time to calibrate a CoalHMM model for figuring out some speciation and population genetics parameters of ancestral species.
No definitive answer came up at the meeting, but there was a short discussion by email after the meeting. This paper was sent around, where the divergence times were estimated to 25MYA and 13MYA, respectively, although the last of those numbers is actually the calibration point used in the analysis, so it is an assumption more than an estimate.
The problem is, the 13MYA used for the calibration is based on fossil evidence, and as far as I can see, that would make it an estimate for the speciation time between human and orangutan. We need the sequence divergence time. Speciation time and divergence time can vary with millions of years (if the effective population size is large enough).
If 13MYA is the divergence time between human and orangutan, we get a speciation time that is unrealistically recent. If the divergence time is 18MYA instead, as we assumed in this paper, we would get a speciation time around 12MYA which would match the MBE paper.
But how do you figure out the divergence time needed to calibrate the clock? Is there any way to get it, rather than the speciation time, from fossil evidence?
For our purposes, I suppose we can just as well work with speciation times for our calibration, but not everyone is using CoalHMMs for their analysis, so how do you deal with this problem?
May 29th, 2008 at 8:59 am
Scott Edwards talked about this problem at ESEB in Uppsala last year. The speciation time gives a bound on the sequence divergence time, obviously, so you can treat the species as being a single population before that. He didn't talk about the mathematical details, but I think the idea is clear, and using several loci in the calibration will help, because it gives you a distribution of coalescent times.
May 29th, 2008 at 9:08 am
This is very close to what we do in our CoalHMM modelling. We estimate a speciation time, an effective population time, and a distribution of coalescence times. Fixing any one of these parameters gives us the values for the rest, but without fixing them we only get relative values. If know the speciation time, we know the average divergence time as well, so that is not a problem. What I was thinking was: how do you calibrate the molecular clock without modelling the population genetics of the speciation event? If you take the fossil evidence -- which gives you bounds on the speciation time -- and use this estimate as the divergence time, you could be off by million of years!
I trust the paleontologists to give us reasonably accurate estimates of speciation times, but we need to correct for the coalescence process to get the molecular clock calibrated!
Of course, modeling the coalescence process before speciation is a very simple model of the speciation event, but at least it is better than assuming that speciation and sequence divergence are both instantaneous.
May 30th, 2008 at 6:00 pm
Welcome to the molecular callibration world.
I also trust the paleontologists to give us reasonably accurate estimates of when an individual of a given species lived and where. For sure they do their best. However, so far, I think we have been doing a bad job when using those points of callibration for molecular dating.
When someone dates two fossils, let's say between human and orang to 13MYA, this means, that 13MYA the two species could already be differentiated as we see them today. To my mind there are two main problems. First, as you said this will be closer to the speciation time, but how closer? They could have been separated since 20 MYA and we only found fossils from 13MYA. Thus, this is always a minimun date. Considering this date as a speciation date, we are setting the minimum time backwards in time that we can consider them as different species. The fossil record is probably a small sample from where and when existed a species.
Secondly, I guess this is a minor problem to primates but major for many other species, specially when the fossil record is incomplete. There is an underlying assumption: we assume that the fossil we see is representative, for instance in Orangutan, but this is only true if we assume that the main chracteristics to distinguish species did not change during 13MYA. This is, that human and Orang showed more or less the same morphological differences 13MYA as today. AS I said this is probably not a problem to primates, but for many species, with fragmentary data, I think it is....
However this the best so far we can do.
I agree this generates your question and then when you consider your argument, then the speciation time will be very recent....and then you get in some circularity.
May 31st, 2008 at 6:40 am
If you find a fossil you believe to be a common ancestor of human and orang at, say 14MYA and you find fossils you believe to be an ancestor of only humans at 10MYA, you can reasonably assume that the speciation occurred 10-14MYA. If you only have one of the two, you only have a lower or upper bound, as you say.
An estimate giving you a range of 4MYA is still pretty good. Especially if you have a couple of such estimates.
The problem is, the divergence time could be much earlier than 14MYA, depending on the average coalescence time (the effective population size).
I don't think fossil evidence alone is enough to figure these things out. Molecular data is needed as well.
I guess it all comes down to having enough fossil calibration points to figure out speciation times, then having enough molecular data to model the speciaiton process. If you use a calibration point that leads to obviously incorrect dates elsewhere in your inference, you have a problem, but otherwise it is probably not too bad...