A new paper in PLoS Computational Biology challenges conventional thought on orthologs and paralogs, and may — if its conclusions are true — bring the foundation of genome biology into question, says Richard Grant at The Scientist's Naturally Selected blog. In what is known as the "ortholog conjecture," it is assumed that orthologous genes have the same, or closely related, functions. The new paper challenges this conjecture — "paralogs are often a much better predictor of function than are orthologs," the authors write. But in a published dissent to the paper in F1000, NIH's Michael Galperin disputes this conclusion, and argues that the authors failed to compare functions of orthologs in two "reasonably well characterized genomes," and instead compared Gene Ontology annotations for orthologs and paralogs. In other words, Grant says, they did a meta-analysis of what others have said about the problem, rather than studying the problem itself. Galperin says that the paper's conclusions are wrong, and "the key principle of comparative genomics is safe for now."