Prediction of Gene Function
When Jonathan Eisen originally coined phylogenomics, it applied to prediction of gene function. Before the use of phylogenomic techniques, predicting gene function was done primarily by comparing the gene sequence with the sequences of genes with known functions. When several genes with similar sequences but differing functions are involved, this method alone is ineffective in determining function. A specific example is presented in the paper “Gastronomic Delights: A movable feast”. Gene predictions based on sequence similarity alone had been used to predict that Helicobacter pylori can repair mismatched DNA. This prediction was based on the fact that this organism has a gene for which the sequence is highly similar to genes from other species in the "MutS" gene family which included many known to be involved in mismatch repair. However, Eisen noted that H. pylori lacks other genes thought to be essential for this function (specifically, members of the MutL family). Eisen suggested a solution to this apparent discrepancy - phylogenetic trees of genes in the MutS family revealed that the gene found in H. pylori was not in the same subfamily as those known to be involved in mismatch repair. Furthermore he suggested that this "phylogenomic" approach could be used as a general method for prediction functions of genes. This approach was formally described in 1998. For reviews of this aspect of phylogenomics see Brown D, Sjölander K. Functional classification using phylogenomic inference.
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