A class of identifiable phylogenetic birth-death models.

In a striking result, Louca and Pennell [S. Louca, M. W. Pennell, Nature 580, 502-505 (2020)] recently proved that a large class of phylogenetic birth-death models is statistically unidentifiable from lineage-through-time (LTT) data: Any pair of sufficiently smooth birth and death rate functions is "congruent" to an infinite collection of other rate functions, all of which have the same likelihood for any LTT vector of any dimension. As Louca and Pennell argue, this fact has distressing implications for the thousands of studies that have utilized birth-death models to study evolution. In this paper, we qualify their finding by proving that an alternative and widely used class of birth-death models is indeed identifiable. Specifically, we show that piecewise constant birth-death models can, in principle, be consistently estimated and distinguished from one another, given a sufficiently large extant timetree and some knowledge of the present-day population. Subject to mild regularity conditions, we further show that any unidentifiable birth-death model class can be arbitrarily closely approximated by a class of identifiable models. The sampling requirements needed for our results to hold are explicit and are expected to be satisfied in many contexts such as the phylodynamic analysis of a global pandemic.

Identifiability and inference of phylogenetic birth-death models.

Recent theoretical work on phylogenetic birth-death models offers differing viewpoints on whether they can be estimated using lineage-through-time data. Louca and Pennell (2020) showed that the class of models with continuously differentiable rate functions is nonidentifiable: any such model is consistent with an infinite collection of alternative models, which are statistically indistinguishable regardless of how much data are collected. Legried and Terhorst (2022) qualified this grave result by showing that identifiability is restored if only piecewise constant rate functions are considered. Here, we contribute new theoretical results to this discussion, in both the positive and negative directions. Our main result is to prove that models based on piecewise polynomial rate functions of any order and with any (finite) number of pieces are statistically identifiable. In particular, this implies that spline-based models with an arbitrary number of knots are identifiable. The proof is simple and self-contained, relying mainly on basic algebra. We complement this positive result with a negative one, which shows that even when identifiability holds, rate function estimation is still a difficult problem. To illustrate this, we prove some rates-of-convergence results for hypothesis testing using birth-death models. These results are information-theoretic lower bounds which apply to all potential estimators.

Rates of convergence in the two-island and isolation-with-migration models.

A number of powerful demographic inference methods have been developed in recent years, with the goal of fitting rich evolutionary models to genetic data obtained from many populations. In this paper we investigate the statistical performance of these methods in the specific case where there is continuous migration between populations. Compared with earlier work, migration significantly complicates the theoretical analysis and requires new techniques. We employ the theories of phase-type distributions and concentration of measure in order to study the two-island and isolation-with-migration models, resulting in both upper and lower bounds on rates of convergence for parametric estimators in migration models. For the upper bounds, we consider inferring rates of coalescent and migration on the basis of directly observing pairwise coalescent times, and, more realistically, when (conditionally) Poisson-distributed mutations dropped on latent trees are observed. We complement these upper bounds with information-theoretic lower bounds which establish a limit, in terms of sample size, below which inference is effectively impossible.

Impossibility of Consistent Distance Estimation from Sequence Lengths Under the TKF91 Model.

We consider the problem of distance estimation under the TKF91 model of sequence evolution by insertions, deletions and substitutions on a phylogeny. In an asymptotic regime where the expected sequence lengths tend to infinity, we show that no consistent distance estimation is possible from sequence lengths alone. More formally, we establish that the distributions of pairs of sequence lengths at different distances cannot be distinguished with probability going to one.

Polynomial-Time Statistical Estimation of Species Trees Under Gene Duplication and Loss.

Phylogenomics-the estimation of species trees from multilocus data sets-is a common step in many biological studies. However, this estimation is challenged by the fact that genes can evolve under processes, including incomplete lineage sorting (ILS) and gene duplication and loss (GDL), that make their trees different from the species tree. In this article, we address the challenge of estimating the species tree under GDL. We show that species trees are identifiable under a standard stochastic model for GDL, and that the polynomial-time algorithm ASTRAL-multi, a recent development in the ASTRAL suite of methods, is statistically consistent under this GDL model. We also provide a simulation study evaluating ASTRAL-multi for species tree estimation under GDL.