Comparing genomic expression patterns across species identifies shared transcriptional profile in aging

Abstract

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.Gene expression profiling measures the expression levels of thousands of genes at once 1,2 . Most expression profiling studies have focused on the specific genes that respond to specific conditions, but another important direction in functional genomics is to derive insight from global patterns of gene expression. Genome-scale expression patterns have been used as physiological 'fingerprints' for classifying tumors 3,4 and assigning uncharacterized mutations and drugs to known pathways 5 . Because they use information from many genes at once, patterns have great discriminating power, even when the transcriptional effects on individual genes are small 5,6 .The patterns of changes in gene expression observed in microarray experiments can be extensive and complex. To try to analyze these patterns, we exploited the principle that important biological processes are often conserved between organisms. We present an approach to comparative functional genomics based on shared patterns of regulation across orthologous genes. We also present a method for identifying conserved biological components of those patterns that correspond to Gene Ontology categories. These methods can be used to search databases of microarray experiments to discover connections among biological processes in different organisms. RESULTS Comparing genomic expression patterns across speciesWe used phylogenetic analysis to systematically identify orthologous groups of genes for all pairwise comparisons between C. elegans, D. melanogaster, Saccharomyces cerevisiae and Homo sapiens (Supplementary Tables 1-5 online). For C. elegans and D. melanogaster, we identified 3,851 most-conserved orthologous gene pairs (Fig. 1a).We used DNA microarrays in each organism to compare gene expression under different conditions (Fig. 1b). We then used gene phylogenetic relationships to match systematically the measurements of differential expression between orthologous genes from the tw...

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