Inferring Species Trees from Incongruent Multi-Copy Gene Trees Using the Robinson-Foulds Distance

We present a new method for inferring species trees from multi-copy gene trees. Our method is based on a generalization of the Robinson-Foulds (RF) distance to multi-labeled trees (mul-trees), i.e., gene trees in which multiple leaves can have the same label. Unlike most previous phylogenetic methods using gene trees, this method does not assume that gene tree incongruence is caused by a single, specific biological process, such as gene duplication and loss, deep coalescence, or lateral gene transfer. We prove that it is NP-hard to compute the RF distance between two mul-trees, but it is easy to calculate the generalized RF distance between a mul-tree and a singly-labeled tree. Motivated by this observation, we formulate the RF supertree problem for mul-trees (MulRF), which takes a collection of mul-trees and constructs a species tree that minimizes the total RF distance from the input mul-trees. We present a fast heuristic algorithm for the MulRF supertree problem. Simulation experiments demonstrate that the MulRF method produces more accurate species trees than gene tree parsimony methods when incongruence is caused by gene tree error, duplications and losses, and/or lateral gene transfer. Furthermore, the MulRF heuristic runs quickly on data sets containing hundreds of trees with up to a hundred taxa.Comment: 16 pages, 11 figure

The inference of gene trees with species trees

Molecular phylogeny has focused mainly on improving models for the reconstruction of gene trees based on sequence alignments. Yet, most phylogeneticists seek to reveal the history of species. Although the histories of genes and species are tightly linked, they are seldom identical, because genes duplicate, are lost or horizontally transferred, and because alleles can co-exist in populations for periods that may span several speciation events. Building models describing the relationship between gene and species trees can thus improve the reconstruction of gene trees when a species tree is known, and vice-versa. Several approaches have been proposed to solve the problem in one direction or the other, but in general neither gene trees nor species trees are known. Only a few studies have attempted to jointly infer gene trees and species trees. In this article we review the various models that have been used to describe the relationship between gene trees and species trees. These models account for gene duplication and loss, transfer or incomplete lineage sorting. Some of them consider several types of events together, but none exists currently that considers the full repertoire of processes that generate gene trees along the species tree. Simulations as well as empirical studies on genomic data show that combining gene tree-species tree models with models of sequence evolution improves gene tree reconstruction. In turn, these better gene trees provide a better basis for studying genome evolution or reconstructing ancestral chromosomes and ancestral gene sequences. We predict that gene tree-species tree methods that can deal with genomic data sets will be instrumental to advancing our understanding of genomic evolution.Comment: Review article in relation to the "Mathematical and Computational Evolutionary Biology" conference, Montpellier, 201

The Mathematics of Phylogenomics

The grand challenges in biology today are being shaped by powerful high-throughput technologies that have revealed the genomes of many organisms, global expression patterns of genes and detailed information about variation within populations. We are therefore able to ask, for the first time, fundamental questions about the evolution of genomes, the structure of genes and their regulation, and the connections between genotypes and phenotypes of individuals. The answers to these questions are all predicated on progress in a variety of computational, statistical, and mathematical fields. The rapid growth in the characterization of genomes has led to the advancement of a new discipline called Phylogenomics. This discipline results from the combination of two major fields in the life sciences: Genomics, i.e., the study of the function and structure of genes and genomes; and Molecular Phylogenetics, i.e., the study of the hierarchical evolutionary relationships among organisms and their genomes. The objective of this article is to offer mathematicians a first introduction to this emerging field, and to discuss specific mathematical problems and developments arising from phylogenomics.Comment: 41 pages, 4 figure

Supertree-like methods for genome-scale species tree estimation

A critical step in many biological studies is the estimation of evolutionary trees (phylogenies) from genomic data. Of particular interest is the species tree, which illustrates how a set of species evolved from a common ancestor. While species trees were previously estimated from a few regions of the genome (genes), it is now widely recognized that biological processes can cause the evolutionary histories of individual genes to differ from each other and from the species tree. This heterogeneity across the genome is phylogenetic signal that can be leveraged to estimate species evolution with greater accuracy. Hence, species tree estimation is expected to be greatly aided by current large-scale sequencing efforts, including the 5000 Insect Genomes Project, the 10000 Plant Genomes Project, the (~60000) Vertebrate Genomes Project, and the Earth BioGenome Project, which aims to assemble genomes (or at least genome-scale data) for 1.5 million eukaryotic species in the next ten years. To analyze these forthcoming datasets, species tree estimation methods must scale to thousands of species and tens of thousands of genes; however, many of the current leading methods, which are heuristics for NP-hard optimization problems, can be prohibitively expensive on datasets of this size. In this dissertation, we argue that new methods are needed to enable scalable and statistically rigorous species tree estimation pipelines; we then seek to address this challenge through the introduction of three supertree-like methods: NJMerge, TreeMerge, and FastMulRFS. For these methods, we present theoretical results (worst-case running time analyses and proofs of statistical consistency) as well as empirical results on simulated datasets (and a fungal dataset for FastMulRFS). Overall, these methods enable statistically consistent species tree estimation pipelines that achieve comparable accuracy to the dominant optimization-based approaches while dramatically reducing running time

TRACTION: Fast Non-Parametric Improvement of Estimated Gene Trees

Gene tree correction aims to improve the accuracy of a gene tree by using computational techniques along with a reference tree (and in some cases available sequence data). It is an active area of research when dealing with gene tree heterogeneity due to duplication and loss (GDL). Here, we study the problem of gene tree correction where gene tree heterogeneity is instead due to incomplete lineage sorting (ILS, a common problem in eukaryotic phylogenetics) and horizontal gene transfer (HGT, a common problem in bacterial phylogenetics). We introduce TRACTION, a simple polynomial time method that provably finds an optimal solution to the RF-Optimal Tree Refinement and Completion Problem, which seeks a refinement and completion of an input tree t with respect to a given binary tree T so as to minimize the Robinson-Foulds (RF) distance. We present the results of an extensive simulation study evaluating TRACTION within gene tree correction pipelines on 68,000 estimated gene trees, using estimated species trees as reference trees. We explore accuracy under conditions with varying levels of gene tree heterogeneity due to ILS and HGT. We show that TRACTION matches or improves the accuracy of well-established methods from the GDL literature under conditions with HGT and ILS, and ties for best under the ILS-only conditions. Furthermore, TRACTION ties for fastest on these datasets. TRACTION is available at https://github.com/pranjalv123/TRACTION-RF and the study datasets are available at https://doi.org/10.13012/B2IDB-1747658_V1