shape of a finch's beak may be associated with its foraging behaviour. However, it is not advisable to search for these associations by the direct comparison of measurements or genetic sequences because these observations are not independent because of their descent from common ancestors. For discrete characters, this problem was first addressed in the framework of maximum parsimony by evaluating whether two characters tended to undergo a change on the same branches of the tree. Felsenstein identified this problem for continuous character evolution and proposed a solution similar to ancestral reconstruction, in which the phylogenetic structure of the data was accommodated statistically by directing the analysis through computation of "independent contrasts" between nodes of the tree related by non-overlapping branches. Molecular evolution On a molecular level, amino acid residues at different locations of a protein may evolve non-independently because they have a direct physicochemical interaction, or indirectly by their interactions with a common substrate or through long-range interactions in the protein structure. Conversely, the folded structure of a protein could potentially be inferred from the distribution of residue interactions. One of the earliest applications of ancestral reconstruction, to predict the three-dimensional structure of a protein through residue contacts, was published by Shindyalov and colleagues. Phylogenies relating 67 different protein families were generated by a distance-based clustering method (unweighted pair group method with arithmetic mean, UPGMA), and ancestral sequences were reconstructed by parsimony. The authors reported a weak but significant tendency for co-evolving pairs of residues to be co-located in the known three-dimensional structure of the proteins. The reconstruction of ancient proteins and DNA sequences has only recently become a significant scientific endeavour. The developments of extensive genomic sequence databases in conjunction with advances in biotechnology and phylogenetic inference methods have made ancestral reconstruction cheap, fast, and scientifically practical. This concept has been applied to identify co-evolving residues in protein sequences using more advanced methods for the reconstruction of phylogenies and ancestral sequences. For example, ancestral reconstruction has been used to identify co-evolving residues in proteins encoded by RNA virus genomes, particularly in HIV. Ancestral protein and DNA reconstruction allows for the recreation of protein and DNA evolution in the laboratory so that it can be studied directly. With respect to proteins, this allows for the investigation of the evolution of present-day molecular structure and function. Additionally, ancestral protein reconstruction can lead to the discoveries of new biochemical functions that have