Argweaver uses a generation time of 25 years with a mutation rate of 1.26e-8 mutations per generation, which is equivalent to a mutation rate of 0.52e-9 mutations per year.
Is this the correct number?
Directly Measured Mutation Rates
In the genomic age, with easy sequencing, we can now directly measure the mutation rate. Without getting into the details, there are several ways we can do this. More than one method. A recent review, coallates this recent data, and Figure 1 has all we need to assess the mutation rate more carefully. The mutation rate in human evolution and demographic inference - ScienceDirect
Each color is a different method, and we can see that they are pretty close, centered at about 0.5e-9. This is a result computed from several different studies, using several different methods, which all give us about the same result. This means that ArgWeaver is using an appropriate mutation rate, determined by several independent methods.
Variation in Mutation Rates
Yes, there is variation in mutation rate.
However, the complex effects we see, for example, in the Lenski experiment (which was referenced in this conversation, The dynamics of molecular evolution over 60,000 generations | Nature) are not relevant to this problem. Look at figure 2 from the Lenski paper, which shows how mutation rate varies in each experiment. Look at panel B.
Here we can see there are two groups. One group (red and orange) are mutators, that at some point start rapidly mutating much more than the normal rate. One group (blue - purple) are non-mutators which are just mutating a a more normal rate. The key point is that there is a wild difference between these two groups.
However, this wild of variation in mutation rates is not relevant to mammalian populations. There is much much more constraints on mammalian germline mutation rates, and we do not see such wild swings between populations. So this is an example of an effect in the Lenski experiment that we do not need to account for when studying human DNA. Adding to that pattern, we know that much more of the human genome is non-coding than in bacteria, so it will be more clock like too.
We can measure it in different populations, and we can even detect some differences in the past. These variations, however, in humans are all relatively small. These variations, also, are not always to higher mutation rates, but also to lower mutation rates. So yes, it is likely that mutation rates were slightly higher in particular populations or points in the past (let’s say within 2-fold per year), but it is also likely they were slightly lower at times too. For the most part, this just averages out over long periods when looking at the whole human population. That is not 100% true, but the law of averages is why variation in mutation rate is not going to dramatically increase our confidence interval on TMR4A by much.
Yes, we do expect some variation, but it’s hard to imagine that variation being more than just 10 to 20% when averaged over 10s of thousands of years.
How Much Faster for a TMR4A of 100 kya or 6 kya.
How much faster would we have to see mutation to find a TMR4A a much lower level.
-
If TMR4A was at 100 kya, we would expect the mutation rate to be 2.1e-8 per generation, or 4x more than observed.
-
If TMR4A was at 6 kya, we would expect the mutation rate to be 32e-8 per generation, or 64x more than observed.
We can see that both these rates are well outside the range we see in the observed rates. It is just not likely that a bottleneck of single couple took place at 100 kya, and its entirely inconsistent with the evidence at 6 kya.