Keruru has uncovered some interesting things in his review of the mathematics underlying Kimura’s cancellation, which I have shown is a) incorrect for most species and b) a Portuguese mathematician has shown to be mathematically incorrect:
In February I argued that the mathematics underwriting neutral theory was broken. The argument had two legs. The first, drawn from a preprint I had read approvingly, held that Kimura’s substitution-rate identity
k = μrests on an equivocation: that the effective population size N<sub>e</sub> is made to stand for two incompatible quantities — a mutation-supply term and a drift term — which are then cancelled against each other. The second was empirical: an ancient-DNA analysis reporting essentially zero allele fixations across a million loci in the 240 generations separating Early Neolithic Europe from the present.Both legs have given way. I want to set out how, because the manner of their failure is more interesting than the original claim, and because the instinct behind the essay turns out to have been sound while its aim was off by about thirty degrees.
The equivocation that isn’t
Written as
k = 2N_e μ × 1/(2N_e) = μ, the objection looks devastating. Mutation supply is a biochemical fact about replicating cells and scales with the number of individuals actually reproducing. Drift is a statistical fact about sampling variance and scales with something much smaller and considerably slipperier. Two different numbers wearing the same symbol, cancelled against each other, yielding a result that has calibrated half of molecular anthropology.The trouble is that the derivation does not require N<sub>e</sub> in either position, and the textbook notation is simply careless.
Mutation supply is
2Nμwith N the census count — mutations occur in gametes, and every reproducing individual contributes gametes. The fixation probability of a single new neutral mutant is its initial frequency, and one new copy among 2N copies has frequency1/(2N)— census again. The two census terms cancel. N<sub>e</sub> never enters, and so cannot be equivocated upon.Why is the fixation probability equal to the initial frequency? Not by assumption. Under neutrality the expected change in allele frequency each generation is zero, which makes the frequency a bounded martingale; a bounded martingale that must eventually be absorbed at 0 or 1 has absorption probability at 1 equal to its starting value. That is optional stopping, and it is a theorem rather than a modelling convention.
The claim is testable without any diffusion approximation at all, using exact finite Markov chains. I built two. The first is ordinary Wright–Fisher. The second is a sweepstakes model: half the time, half the population is replaced wholesale by clones of a single randomly chosen parent — reproductive skew of the kind documented in Atlantic cod and Pacific oysters, wildly outside anything Wright and Fisher had in mind. Measured from heterozygosity decay, the sweepstakes chain has an effective size 5.6 times smaller than the Wright–Fisher chain at identical census size.
The fixation probability of a single new mutant in both chains: exactly
1/(2N_census), to fifteen decimal places.N<sub>e</sub> can be dragged around by a factor of six and the fixation probability does not move. It follows that my own demographic work on the collapse in variance of reproductive success — a real finding, and one I still stand behind — does not touch the substitution rate. It changes coalescent depth, standing diversity, and every estimate of N<sub>e</sub> derived from them. It leaves
k = μexactly where it was.
First, the problem with Kimura turns out to be even more significant than I originally believed. I was pretty sure that Keruru had been led off track the moment that he mentioned the word “martingale” because that’s the retreat that every AI, including both Claude Athos and the entire Red Team, initially made. You cannot use AI to provide you the answer; you have to know at least the correct shape of the answer before you ask the AI.
I’ll post my full response to Keruru later this week. His work here is very far from valueless, as I will demonstrate, but it is nevertheless incorrect due to his failure to anchor the abstract mathematical elements in material reality. This also, rather fortuitously, demonstrates the importance of the Triveritas, as any one link in the triad is capable of serious error when allowed to operate outside the bounds of the other two.
But the epicycle wasn’t elsewhere. There are multiple epicyles.
k = μ is a correct baseline for asking whether something other than drift is happening. But it is not a rate at which anything can be observed to occur in a sexual, age-structured, demographically non-stationary population — which is every organism anyone cares about.