Keruru retracted his previous endorsement of the N/Nₑ argument, and much to my chagrin, he was right to do so: the derivation of Kimura’s substitution identity never needed Nₑ on either side of the algebraic equation. Supply is 2Nμ in the census N, the fixation probability of a new copy is 1/(2N) in the same N, the two correctly cancel, and the fact that the effective population Nₑ was regularly written into the supply side was nothing more than careless notation by the authors of the biology textbooks over the years, it was not a hidden move by Kimura back in 1968. Thanks to this additional evidence that biologists can’t do math, this error means that it will be necessary to produce a 3rd Edition of Probability Zero to correct my mistake in this regard. Mea maxima culpa, dammit.
The second part of his post is not correct. He says zero fixations across the ancient-DNA window is exactly what neutral theory predicts, so the data cannot discriminate. The arithmetic holds given one number: Nₑ ≈ 10,000 — which comes from θ = 4Nₑμ, which presupposes k = μ, the identity under test. He has retracted an empirical falsification of the clock by feeding in a parameter that the clock manufactures; Charlesworth flagged this exact circularity in 2009, and Keruru himself, two sections later, calls Nₑ “estimated from the quantity it is then used to explain.” He diagnosed the disease in Section 3 and caught it in Section 2. His chains carry it from the other side: they differ in offspring-number variance, never the contested axis, while his sweepstakes parent is drawn uniformly at random — setting the one parameter in dispute, the covariance between who breeds and what they carry, to zero by fiat.
And most crucially, his work never contains a census population. His own supply term at Nₑ = 10,000 gives 740,000 new mutations per generation; Kong et al. (2012) times the global birth rate gives 2.5 × 10¹¹, a factor of 330,000 — which does not touch his repaired algebra but demolishes the literature that algebra abandons. He rescued three lines and orphaned fifty-seven years of applying them. Then he names frequency drift as “the analysis that should have been run.” As it happens, I ran it while writing the first edition of PZ: the Allen Ancient DNA Resource, 1,372 Neolithic against 680 modern Europeans, has rs35619459 moving 29.3% → 91.3%, a twelve-sigma excursion against his own stated expectation, and a drift-variance Nₑ near 2 rather than ten thousand. The signal is the size of a population turnover — structure, non-exchangeability, the very thing his model pinned at zero.
Nevertheless, I owe him a considerable debt of gratitude and not just for pointing out my mistake. For, as we’ve repeatedly seen over the course of this project, the identification of one particular flaw, and the subsequent process of correcting it, has led to a new discovery. The mechanism he reached for in the second part— that the fixation time is so enormous almost nothing destined to fix finishes inside the window — is exactly right, and it turned out to be the most productive thing in the exchange. He relied upon it to argue the data cannot test the clock; but when it is reversed, that same mechanism does not protect the clock, it provides a time limit. If the chance a destined allele completes within T generations scales as exp(−π²Nₑ/T), then k = μ cannot be realized at all in any population large enough for that transit to run 4Nₑ generations — and at census population scale that exponent becomes a ceiling on population size, about ten thousand for a large vertebrate, above which gennetic drift is not slow but entirely shut down.
That is the argument of my new paper entitled The Hard Limits of Fixation Through Genetic Drift which you can read at the preprint site, and it exists only because Keruru identified my mistaken identification of Kimura’s algebraic non-error.
ABSTRACT: The Hard Limits of Fixation Through Genetic Drift,
Kimura’s neutral substitution rate, k = μ, is a steady-state identity: it holds only after a population has held one size for the roughly 4Nₑ generations a neutral allele needs to drift from a single copy to fixation. That transit has never been checked against the number of generations that species lineages have actually had. Checking them yields a hard ceiling on population size, X = (Vₖ + 2)·G/16 — reproductive variance and lineage generations alone, with no mutation rate, no coalescent quantity, and no fitted constant. For a large, long-lived vertebrate the effective ceiling falls to about ten thousand individuals. Above it, a neutral allele’s chance of fixing within the generations its lineage will ever have is not merely small but exponentially small, of order exp(−π²Nₑ/G) — for humans at current size, about one in ten to the seventy-eight-millionth. Humans number more than eight billion, the better part of a million times over the line; the African elephant, endangered at four hundred thousand and falling, is still forty times too abundant for drift to complete to fixation. No vertebrate population is simultaneously large enough to persist as a species and small enough to fix a neutral allele by drift. What substitution these abundant populations show is not produced at their current size; it is residual drainage from the smaller populations they descend from. The domain of k = μ is confined to demographic conditions that no non-endangered species is capable of meeting.
