Statistically consistent and computationally efficient inference of ancestral DNA sequences in the TKF91 model under dense taxon sampling

Abstract

In evolutionary biology, the speciation history of living organisms is represented graphically by a phylogeny, that is, a rooted tree whose leaves correspond to current species and branchings indicate past speciation events. Phylogenies are commonly estimated from molecular sequences, such as DNA sequences, collected from the species of interest. At a high level, the idea behind this inference is simple: the further apart in the Tree of Life are two species, the greater is the number of mutations to have accumulated in their genomes since their most recent common ancestor. In order to obtain accurate estimates in phylogenetic analyses, it is standard practice to employ statistical approaches based on stochastic models of sequence evolution on a tree. For tractability, such models necessarily make simplifying assumptions about the evolutionary mechanisms involved. In particular, commonly omitted are insertions and deletions of nucleotides -- also known as indels. Properly accounting for indels in statistical phylogenetic analyses remains a major challenge in computational evolutionary biology. Here we consider the problem of reconstructing ancestral sequences on a known phylogeny in a model of sequence evolution incorporating nucleotide substitutions, insertions and deletions, specifically the classical TKF91 process. We focus on the case of dense phylogenies of bounded height, which we refer to as the taxon-rich setting, where statistical consistency is achievable. We give the first polynomial-time ancestral reconstruction algorithm with provable guarantees under constant rates of mutation. Our algorithm succeeds when the phylogeny satisfies the "big bang" condition, a necessary and sufficient condition for statistical consistency in this context.