Distance based reconstruction methods
Distance based phylogenetic reconstruction methods use a pairwise distance estimate between the input organisms to reconstruct trees. The distances are an estimate of the evolutionary distance between each pair of organisms which are usually computed from DNA or amino acid sequences. Given two homologous sequences a distance estimate can be computed by aligning the sequences and then counting the number of positions where the sequences differ. The number of differences is called the observed number of substitutions and is usually an underestimate of the real distance as multiple mutations could have occurred at any position.
To correct for these hidden substitutions a substitution model, such as Jukes-Cantor or Kimura 80, can be used to get a more precise distance estimate.
Alternatively, k-mer based methods or SNP based methods can be used to get a distance estimate without the use of substitution models.
After distance estimates have been computed, a phylogenetic tree can be reconstructed using a distance based reconstruction method. Most distance based methods perform a bottom up reconstruction using a greedy clustering algorithm. Initially, each input organism is put in its own cluster which corresponds to a leaf node in the resulting tree. Next, pairs of clusters are iteratively joined into higher level clusters, which correspond to connecting two nodes in the tree with a new parent node. When a single node remains, the tree is reconstructed.
The CLC Drug Discovery Workbench provides two of the most widely used distance based reconstruction methods:
- The UPGMA method [Michener and Sokal, 1957] which assumes a constant rate of evolution (molecular clock hypothesis) in the different lineages. This method reconstruct trees by iteratively joining the two nearest clusters until there is only one cluster left. The result of the UPGMA method is a rooted bifurcating tree annotated with branch lengths.
- The Neighbor Joining method [Saitou and Nei, 1987] attempts to reconstruct a minimum evolution tree (a tree where the sum of all branch lengths is minimized). Opposite to the UPGMA method, the neighbor joining method is well suited for trees with varying rates of evolution in different lineages. A tree is reconstructed by iteratively joining clusters which are close to each other but at the same time far from all other clusters. The resulting tree is a bifurcating tree with branch lenghts. Since no particular biological hypothesis is made about the placement of the root in this method, the resulting tree is unrooted.