Abstract

A versatile method, quartet puzzling, is introduced to reconstruct the topology (branching pattern) of a phylogenetic tree based on DNA or amino acid sequence data. This method applies maximum-likelihood tree reconstruction to all possible quartets that can be formed from n sequences. The quartet trees serve as starting points to reconstruct a set of optimal n-taxon trees. The majority rule consensus of these trees defines the quartet puzzling tree and shows groupings that are well supported. Computer simulations show that the performance of quartet puzzling to reconstruct the true tree is always equal to or better than that of neighbor joining. For some cases with high transition/transversion bias quartet puzzling outperforms neighbor joining by a factor of 10. The application of quartet puzzling to mitochondrial RNA and tRNAVd’ sequences from amniotes demonstrates the power of the approach. A PHYLIP-compatible ANSI C program, PUZZLE, for analyzing nucleotide or amino acid sequence data is available.