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Goals of Phylogenetic Analysis. Given a multiple sequence alignment, determine the ancestral relationships among the species. We assume that residues in a column are homologous , and that all columns have the same history. Time. Hu Ch Go Gi. Types of Phylogenetic Methods.
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Goals of Phylogenetic Analysis • Given a multiple sequence alignment, determine the ancestral relationships among the species. • We assume that residues in a column are homologous, and that all columns have the same history. Time Hu Ch Go Gi
Types of Phylogenetic Methods • Character-based • Parsimony • Likelihood • Distance-based • Neighbor joining (NJ) • UPGMA Involve optimizing a criterion based on fit of the residues to the tree. Involve optimizing a criterion based on fit of a matrix of pairwise distances to the tree
A A A B C C C B D D D B We usually estimate unrooted trees For 4 sequences, there are only 3 unique unrooted trees.
A A A C B B C D B D D C Parsimony Methods A ACGA B ATGC C GTGC D GCAA Tree 1 Tree 2 1 2 3 4 Tot Tree 1 1 2 1 2 6 Tree 2 2 2 1 2 7 Tree 3 2 1 1 1 5 Tree 3
B A G Likelihood Methods x is the collection of all parameters affecting the evolution of sequences A, B, and G. is the collection of all data (sequences A, B, and G).
Modeling sequence change • Typically, the evolution of DNA sequences is modeled at the level of single sites. • JC: Jukes-Cantor (1969) • K2P: Kimura (1980) • F81: Felsenstein (1981) • HKY: Hasegawa et al. (1985) • REV: Tavaré (1986)
General Time Reversible Model A C G T A C G T
B A G Under this assumption, the likelihood simplifies to a product of individual site likelihoods: and (Nucleotide in Species A, site k) x
Distance Methods A B C D A 0 B .5 0 C .75 .25 0 D .5 1.0 .75 0 A ACGA B ATGC C GTGC D GCAA
A C B D a c e b d Many distance methods seek to find the tree that minimizes a score such as: