Viral Quasispecies Evolution as a Branching Random Walk on the Hypercube

Abstract

We study a continuous-time nearest-neighbor branching random walk on the $d$-dimensional $b$-ary hypercube $\{0,1,\dots ,b-1{\}}^d$ as a model for viral quasispecies evolution under mutation and replication. Motivated by mutagenic antiviral treatments and evolutionary-safety questions, we analyze the first passage time to a fixed target genotype at Hamming distance $m$, corresponding to the first appearance of a prescribed collection of mutations. We derive sharp asymptotics for these first passage times, uniformly for $m\le d/L$ as $d\to \infty$ (where $L>0$ is a large constant), and identify a phase transition in first-passage scaling at $\ddot{I}=e$, where $\ddot{I}$ denotes the effective growth parameter. In the slow-branching regime $\ddot{I}\in (1,e)$ relevant to mutagenic treatment scenarios, the first passage time is asymptotically affine in the genome length $d$ and the target distance $m$. In particular, when replication is fixed and mutation exceeds branching, increasing the mutation rate can delay the first appearance of a prescribed genotype by order $d$, providing a quantitative perspective on evolutionary safety.

43 pages, 2 figures