1. Phylogenetic prediction of gene function Daniel Barker Centre for Evolution, Genes and Genomics, School of Biology, University of St Andrews http://biology.st-andrews.ac.uk/cegg

2. Gene A 1 0 1 0 1 0 1 0 Gene B 1 0 1 0 1 0 1 0 Gene C 1 1 1 1 0 0 0 0 Gene D 1 1 1 1 0 0 0 0 sp. i sp. ii sp. iii sp. iv sp. v sp. vi sp. vii sp. viii Correlations in gene gain/loss

3. S. cerevisiae S. paradoxus S. mikatae S. bayanus S. castellii Saccharomyces kluyveri Candida albicans Schizosaccharomyces pombe Fusarium graminearum Neurospora crassa Magnaporthe grisea Aspergillus nidulans Cryptococcus neoformans Drosophila melanogaster Caenorhabditis elegans 1 1 0 0 1 1 0 1 1 1 0 0 0 1 0 0 1 1 0 0 0 1 CIN4 ORC3 L9A L42B 0.1 changes per nucleotide The ‘traditional’ across-species method of phylogenetic profiles (Pellegrini et al. 1999, PNAS 96: 4285–7288) returns a false positive functional link for the pair of proteins {CIN4, ORC3} and a false negative for the pair {L9A, L42B}. The tree-based, maximum likelihood phylogenetic method returns the ‘correct’ result for both pairs (Barker & Pagel 2005, PLoS Comp Biol 1:24–31). Example

4. 1.0 0.5 0.2 0.1 0.05 0.01 0.005 0.001 0.00090.00080.0007 0.0006 0.00050.00040.00030.0002 p-value cut-off 30 40 50 60 70 80 90 100 20 % specificity Validation Test data based on known yeast protein complexes In the Comprehensive Yeast Genome Database ( http://mips.gsf.de/genre/proj/yeast )

5. University of Reading: Mark Pagel Andrew Meade Wellcome Trust Sanger Institute: Valerie Wood (UCL): Antonio Cavallo Funding: BBSRC EPSRC on behalf of Research Councils UK Acknowledgements