Quantitative assessment of relationship between sequence similarity and function similarity

We present an analysis of the relationship between sequence similarity and function similarity for the proteins in four model organisms, i.e., Arabidopsis thaliana, Saccharomyces cerevisiae, Caenorrhabditis elegans, and Drosophila melanogaster. Using a measure of functional similarity based on the three categories of Gene Ontology (GO) classifications (biological process, molecular function, and cellular component), we quantified the correlation between functional similarity and sequence similarity measured by sequence identity or statistical significance of the alignment and compared such a correlation against randomly chosen protein pairs.Various sequence-function relationships were identified from BLAST versus PSI-BLAST, sequence identity versus Expectation Value, GO indices versus semantic similarity approaches, and within genome versus between genome comparisons, for the three GO categories. Our study provides a benchmark to estimate the confidence in assignment of functions purely based on sequence similarity.Large-scale genome sequencing projects have discovered many new proteins. Of all the proteins whose sequences are known, functions have been experimentally determined for only a small percentage [1]. Annotation of a genome involves assignment of functions to proteins in most cases on the basis of sequence similarity. Protein function assignments based on postulated homology as recognized by sequence identity or significant expectation value of alignment are used routinely in genome analysis. Over the past years, many computational methods [2-11] have been developed to predict function through identifying sequence similarity between a protein of unknown function and one or more proteins with experimentally characterized or computationally predicted functions. However, it is widely recognized that functional annotations should be transferred with caution, as the sequence similarity does not guarantee evolutionary or functional relationship. In addition, if