Identifying functional links between genes by evolutionary transcriptomics†
The ability to determine gene expression profiles across distant species presents a unique opportunity to identify functional relationships between genes. In particular, transcriptome data may help to distinguish whether genes with similar expression profiles are functionally related or independent. Recent studies on the evolution of gene expression have revealed a striking amount of divergence across strains and species, a notion which has hitherto not been brought to bear on the problem of detecting functional relationships between genes. Here, we introduce evo-links, a method by which a pair of genes are linked if their expression profiles are consistently more similar within species, while their individual conservation across species is low. We show that genes connected through evo-links are more enriched in known functional interactions than genes linked by conventional correlation measures. The network of linked genes further allows the identification of gene communities which reflect distinct functional pathways. We classified communities into major cell-types and derived a temporal developmental map of tissue specification in the nematode C. elegans. This map shows the sequential activation of the endoderm, body wall muscle, and neuronal tissues, and later the pharynx. We propose that as comparative transcriptomics becomes increasingly feasible, evo-links offer a robust method to detect functional relationships and disentangle developmental pathways in data lacking spatial resolution.
- This article is part of the themed collection: Molecular BioSystems Emerging Investigators 2012