Reversibility and Stochastic Networks VI: The Ewens Sampling Distribution Is Consistent Under Sampling Without ReplacementTextbook
Motivation
The neutral theory of molecular evolution holds that much of the genetic variation observed at the molecular level is caused by selectively neutral mutations rather than by selection. To test it against data one needs the distribution of allele frequencies that a neutral model predicts, and in practice that distribution has to be compared with a sample from the population, never with the whole population. Ewens (Ewens 1972) derived the equilibrium distribution of allele counts under the infinite alleles model, now called the Ewens sampling formula; it underlies classical tests of neutrality and appears throughout combinatorics and probability as the law of the cycle type of an Ewens-distributed random permutation and of the Chinese restaurant process.
Chapter 7 of F. P. Kelly, Reversibility and Stochastic Networks (Wiley, 1979) obtains the infinite alleles model as a limit of the reversible migration processes of Chapters 2 and 6, and uses reversibility to answer questions about allele ages and fixation. The mission formalizes the finite, combinatorial results of that chapter.
Timeline. Kimura and Crow (1964) introduced the infinite alleles model. Ewens (1972) found its equilibrium sampling distribution (7.6). Kingman (1978, J. London Math. Soc.) characterized the consistency of random partitions under sampling, the property Theorem 7.1 asserts for the Ewens family. Kelly (1979, Chapter 7) derived (7.6) as a limit of reversible migration processes, and the consistency and the allele-age results from the reversibility of a labelled population process.
Setting
A population consists of individuals, each carrying an allelic type. Its description is , where is the number of allelic types carried by exactly individuals, so that
For a real parameter , the Ewens distribution on descriptions is
where is the binomial coefficient for real . In the infinite alleles model, individuals die at rate , each death is followed by the birth of an offspring of a uniformly chosen survivor, and the offspring is a mutant of an entirely new type with probability ; then (7.6) is the equilibrium distribution with (7.5).
A random sample of size without replacement is a uniformly random -element subset of the labelled individuals, each of the subsets being equally likely; the sample has a description in the same sense.
The number of individuals carrying one given allele performs a random walk on with intensities
An allele is quasi-fixed when it is the only allele present ().
Formalization targets
Goal: consistency under sampling (Theorem 7.1)
If and the population description is distributed as , then a random sample of size drawn without replacement has description with probability , the same being used for both sizes:
Milestones
- (7.6) is a distribution: and (Exercise 7.1.3).
- Theorem 7.1 for , the case the book's proof establishes first.
- Corollary 7.5, the identity of its proof: the probability that a uniformly chosen individual's allele is carried by exactly individuals is
- Theorem 7.9: the probability that the walk (7.8) started at reaches before satisfies
Significance
The results. Consistency under sampling is what makes the Ewens formula usable as a statistical model: the predicted distribution for an observed sample does not depend on the unknown population size, only on . Kelly deduces from it the sufficiency of the number of alleles in a sample for and the heterozygosity (Exercises 7.1.5, 7.1.8). The formula (7.9) gives the equilibrium frequency of the oldest allele, and Theorem 7.9 gives the quasi-fixation probability from which the mean time between quasi-fixations follows (Corollary 7.10).
Formalizing them. All four results are classical and proved; none has a machine-checked proof on the platform or in Mathlib as of this writing. The mission produces a reusable formal Ewens distribution over integer partitions, a definition of sampling without replacement by counting labelled subsets, and an absorption probability for an explicit birth–death walk. Proofs independent of Kelly's process argument are welcome.
Difficulty
The book's proof of Theorem 7.1 is a process argument: in a population whose size fluctuates between and , a drop in size acts as a random deletion, and the truncated equilibrium (7.7) restricted to each size gives and . Turning that into a statement about finite sets requires the equilibrium of a truncated reversible process, which is not available here, so a formal proof must either build that process or find a direct combinatorial route. A direct route has to relate, for each description of the sample, the number of -subsets of a labelled population with a given description to products of binomial coefficients, and sum the result against (7.6); the bookkeeping over partitions is where the work lies. Theorem 7.9 needs a solution of the first-step equations of a non-symmetric walk and the identification of that solution with a hitting probability defined as a limit.
Formalization scope
- Descriptions of individuals are integer partitions
Nat.Partition n, with the multiplicity of the part ; the product in (7.6) runs over . The real binomial coefficient is the published definitionAppliedComb.GenFun.binomReal. - The population is
Fin Mwith allelic typesFin M → ℕ; the description of a labelled set is computed from the labelling. The sampling probability is times the number of -subsets whose restricted labelling has the given description. It is not defined by a formula on descriptions, and a definition that removed individuals one at a time in proportion to class sizes (the book's proof route) is ruled out as a definition because it presupposes the reduction the proof must supply. - The goal and Corollary 7.5 quantify over an arbitrary choice of labelling for each population description. They assume , as required by the chapter's rule that a parent is chosen among the other individuals; the goal also assumes . Because , this forces the conditional sampling law to depend on the population only through its description. Types are natural numbers, so every description is realized and the hypothesis is never vacuous.
- The quasi-fixation probability is defined through the jump chain of (7.8): the limit of the probabilities of reaching within jumps without reaching . The theorem assumes , , and .
- Corollary 7.5 is formalized as the identity of its proof. The identification of the oldest allele's frequency with that of a randomly chosen individual uses allele ages and the reversibility of the labelled process (Theorem 7.2) and is not formalized. Theorem 7.2 itself, whose state space orders the allele labels within each class, and the allele-age results (Corollaries 7.3, 7.4, 7.7, 7.8, Theorem 7.6, Corollary 7.10, Theorem 7.11) are not part of the mission.
Contributions of general partition and sampling lemmas (counting subsets with a given description, the generating function identity ) are reusable beyond this mission.
Selected references
- F. P. Kelly, Reversibility and Stochastic Networks, Wiley, 1979, Chapter 7. https://www.statslab.cam.ac.uk/~frank/BOOKS/kelly_book.html
- W. J. Ewens, The sampling theory of selectively neutral alleles, Theoretical Population Biology 3 (1972), 87–112. https://doi.org/10.1016/0040-5809(72)90035-4
- J. F. C. Kingman, The representation of partition structures, Journal of the London Mathematical Society (2) 18 (1978), 374–380. https://doi.org/10.1112/jlms/s2-18.2.374
- M. Kimura and J. F. Crow, The number of alleles that can be maintained in a finite population, Genetics 49 (1964), 725–738. https://doi.org/10.1093/genetics/49.4.725