Inclusion of pseudogenes in the Ensembl comparative genomics resources

Pseudogenes are segments of DNA that are related to functional genes but have lost functionality, often from the accumulation of multiple mutations. Pseudogenes can thus be found and annotated using sequence similarity, and linked to a parent or source gene, giving us insights into the history of this gene. However, very few resources consider pseudogenes when running comparative genomics analyses, and pseudogenes are largely missing from the major orthology databases. Ensembl is a platform that provides integrated genomics resources of more than 100 vertebrate species and a comprehensive comparative genomics database. Currently, this includes phylogenetic trees and orthology calls across all functional genes. In this work, we extend the Ensembl resources to include pseudogenes at multiple levels to help understanding their evolution. First, we link the pseudogenes to their closest functional homologue with PseudoPipe (Zhang et al., Bioinformatics, 2006), an existing homology-based pseudogene identification pipeline. Then we update the multiple-sequence alignments and phylogenetic trees of their functional counterparts by constraining the original alignment and topology. We are thus able to supplement our orthology predictions with pseudogenes-to-functional orthologues (such as unitary pseudogenes), and between-pseudogenes orthologues. Finally, we run our quality-assessment analyses based on conservation of local gene order and congruence with whole-genome alignments. We will present the results and some statistics of this approach on a test dataset comprising human and rodents, giving insights into the recent evolution of pseudogenes. We will also present prototype Ensembl comparative genomics displays (phylogenetic tree, orthologue and paralogue lists) that include pseudogenes, and we are seeking feedback before releasing the new data in a future version of Ensembl.