Conjecture on the limiting genetic composition of an exponentially growing cell population

Let N\mathcal{N} be the set of nucleotides, let S\mathcal{S} be the set of genomic sites, and partition the neutral sites as

Sneut=jJS(j).\mathcal{S}_\text{neut}=\bigcup_{j\in J}\mathcal{S}(j).

For χ,ψN\chi,\psi\in\mathcal{N} with χψ\chi\not=\psi, write μχ,ψ(j)\mu^{\chi,\psi}(j) for the mutation rate at sites in S(j)\mathcal{S}(j), and let u(j)u(j) be the initial nucleotide at those sites. Let T\mathcal{T} be the tree indexing the random variables PxP_x, RxR_x, and Mx,rM_{x,r}, and let Bin,μB_i^{n,\mu} denote the population count associated with site ii at population size nn.

Limiting composition conjecture. Suppose

n,nμχ,ψ(j)θχ,ψ(j)[0,),μχ,ψ(j)S(j)ηχ,ψ(j)[0,)n\rightarrow\infty,\qquad n\mu^{\chi,\psi}(j)\rightarrow\theta^{\chi,\psi}(j)\in[0,\infty),\qquad \mu^{\chi,\psi}(j)|\mathcal{S}(j)|\rightarrow\eta^{\chi,\psi}(j)\in[0,\infty)

for all jJj\in J and χ,ψN\chi,\psi\in\mathcal{N} with χψ\chi\not=\psi. Then

iSδn1Bin,μxTr=1RxMx,rδPx\sum_{i\in\mathcal{S}}\delta_{n^{-1}B_i^{n,\mu}}\rightarrow\sum_{x\in\mathcal{T}}\sum_{r=1}^{R_x}M_{x,r}\delta_{P_x}

in distribution, where convergence is in the same sense as in the preceding limit theorem. Here (Px)xT\{}(P_x)_{x\in\mathcal{T}\backslash\{\emptyset\}} has the distribution specified by the branching-process limit, with P=1P_\emptyset=1; (Rx)xT\{}(R_x)_{x\in\mathcal{T}\backslash\{\emptyset\}} is an i.i.d. family of geometric random variables with parameter (α(u)β(u))/(α(u)+β(u))(\alpha(u')-\beta(u'))/(\alpha(u')+\beta(u')), while RR_\emptyset is independent of (Rx)(R_x) and satisfies R=dR01R_\emptyset\overset{d}{=}R_0-1; (Px)(P_x) is independent of (Rx)(R_x) if and only if β(u)=0\beta(u')=0; and (Mx,r)xT,rN(M_{x,r})_{x\in\mathcal{T},r\in\mathbb{N}} is an i.i.d. family of Poisson random variables with mean

jψu(j)ηu(j),ψ(j),\sum_j\sum_{\psi\not=u(j)}\eta^{u(j),\psi}(j),

independent of (Px,Rx)(P_x,R_x).

Sources & referencesView supporting material

Primary source

David Cheek and Tibor Antal, “Genetic composition of an exponentially growing cell population”, arXiv:1905.12355 (2020).

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