Least squares inference in phylogeny generates a phylogenetic tree based on an observed matrix of pairwise genetic distances and optionally a weight matrix. The goal is to find a tree which satisfies the distance constraints as best as possible. A phylogenetic tree, also called an evolutionary tree or a tree of life, is a tree showing the evolutionary interrelationships among various species or other entities that are believed to have a common ancestor. ...
Genetic distance is a measure of the disimilarity of genetic material between different species or individuals of the same species. ...
Ordinary and weighted least squares
The discrepancy between the observed pairwise distances Dij and the distances Tij over a phylogenetic tree (i.e. the sum of the branch lengths in the path from leaf i to leaf j) is measured by
where the weights wij depend on the least squares method used. Least squares distance tree construction aims to find the tree (topology and branch lengths) with minimal S. This is a non-trivial problem. It involves searching the discrete space of unrooted binary tree topologies whose size is exponential in the number of leaves. For n leaves there are 1 • 3 • 5 • ... • (2n-3) different topologies. Enumerating them is not feasible already for a small number of leaves. Heuristic search methods are used to find a reasonably good topology. The evaluation of S for a given topology (which includes the computation of the branch lengths) is a linear least squares problem. There are several ways to weight the squared errors (Dij − Tij)2, depending on the knowledge and assumptions about the variances of the observed distances. When nothing is known about the errors, or if they are assumed to be independently distributed and equal for all observed distances, then all the weights wij are set to one. This leads to an ordinary least squares estimate. In the weighted least squares case the errors are assumed to be independent (or their correlations are not known). Given independent errors, a particular weight should ideally be set to the variance of the corresponding distance estimate. Sometimes the variances may not be known, but they can be modeled as a function of the distance estimates. In the Fitch and Margoliash method  for instance it is assumed that the variances are proportional to the squared distances. Linear least squares is a mathematical optimization technique to find an approximate solution for a system of linear equations that has no exact solution. ...
Generalized least squares
The ordinary and weighted least squares methods described above assume independent distance estimates. If the distances are derived from genomic data their estimates covary, because evolutionary events on internal branches (of the true tree) can push several distances up or down at the same time. The resulting covariances can be taken into account using the method of generalized least squares, i.e. minimizing the following quantity
|∑ ||wij,kl(Dij − Tij)(Dkl − Tkl) |
|ij,kl || |
where wij,kl are the entries of the inverse of the covariance matrix of the distance estimates. In statistics and probability theory, the covariance matrix is a matrix of covariances between elements of a vector. ...
- PHYLIP, a freely distributed phylogenetic analysis package containing an implementation of the weighted least squares method
- PAUP, a similar package available for purchase
- Darwin, a programming environment with a library of functions for statistics, numerics, sequence and phylogenetic analysis
- ^ Fitch WM, Margoliash E. (1967). Construction of phylogenetic trees. Science 155: 279-84.