Program in Neuroscience, University of California, San Francisco, California 94143, USA.
Departments of Biochemistry and Biophysics, University of California, San Francisco, California 94143, USA.
Department of Physiology, University of California, San Francisco, California 94143, USA.
Department of Biology, University College London, London, UK.
Program in Genetics, University of California, San Francisco, California 94143, USA.
Program in Developmental Biology, University of California, San Francisco, California 94143, USA.
Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA.
Department of Anatomy, University of California, San Francisco, California 94143, USA.
Program in Biophysics, University of California, San Francisco, California 94143, USA.
Programs in Biological and Medical Informatics, University of California, San Francisco, California 94143, USA.
We developed a method for systematically comparing gene expression patterns across organisms using genome-wide comparative analysis of DNA microarray experiments. We identified analogous gene expression programs comprising shared patterns of regulation across orthologous genes. Biological features of these patterns could be identified as highly conserved subpatterns that correspond to Gene Ontology categories. Here, we demonstrate these methods by analyzing a specific biological process, aging, and show that similar analysis can be applied to a range of biological processes. We found that two highly diverged animals, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, implement a shared adult-onset expression program of genes involved in mitochondrial metabolism, DNA repair, catabolism, peptidolysis and cellular transport. Most of these changes were implemented early in adulthood. Using this approach to search databases of gene expression data, we found conserved transcriptional signatures in larval development, embryogenesis, gametogenesis and mRNA degradation.