Testing the ortholog conjecture with comparative functional genomic data from mammals.
Bottom Line: Among paralogs, those found within the same species are consistently more functionally similar than those found in a different species.In addition to offering implications for the computational prediction of protein function, our results shed light on the relationship between sequence divergence and functional divergence.We conclude that the most important factor in the evolution of function is not amino acid sequence, but rather the cellular context in which proteins act.
Affiliation: School of Informatics and Computing, Indiana University, Bloomington, Indiana, USA.Show MeSH
Mentions: Functional similarity was calculated between all pairs of homologous proteins (i.e. those in the same gene family) in human and mouse for which there is experimentally defined function for both members of the pair. These pairs include 2,579 one-to-one orthologs between human and mouse and 21,771 paralogous comparisons of any type. The experiments used to annotate these genes come from 12,204 unique published papers whose results are collected in the Gene Ontology (GO) database; in a later section we carry out an independent analysis using microarray data to measure functional similarity. Figure 1 shows the relationship between experimentally defined functional similarity and protein sequence identity for both orthologous and paralogous pairs.
Affiliation: School of Informatics and Computing, Indiana University, Bloomington, Indiana, USA.