An Integrated Reconciliation Framework for Domain, Gene, and Species Level Evolution

The majority of genes in eukaryotes consist of multiple protein domains that can be independently lost or gained during evolution. This gain and loss of protein domains, through domain duplications, transfers, or losses, has important evolutionary and functional consequences for genes. Yet, most computational methods for studying gene evolution view genes as the basic unit of evolution and assume that evolutionary processes such as duplications and losses act on entire genes, rather than on parts of genes. Specifically, even though it is well understood that domains evolve inside genes and genes inside species, there do not exist any computational frameworks to simultaneously model the evolution of domains, genes, and species and account for their inter-dependency. Here, we develop a three-tree model of domain evolution that explicitly captures the interdependence of domain-, gene-, and species-level evolution. Our model extends the classical phylogenetic reconciliation framework, which infers gene family evolution by comparing gene trees and species tree, by explicitly accounting for domain-level events. The new model decouples domain-level events from gene-level events and provides a much more fine-grained view of gene family and domain family evolution that is easy to interpret. Specifically, we (i) introduce the new three-tree computational framework, (ii) prove that the associated optimization problem is NP-hard, (iii) devise an efficient heuristic solution for the problem, (iv) apply our algorithm to a large dataset of about 4000 domain trees and 7000 gene trees from 12 fly species, and (v) demonstrate the impact of using our new computational framework by comparing the inferred evolutionary histories against those obtained using existing approaches. Our experimental results show that using the new three-tree model has a significant impact on the inference of both domain-level and gene-level events, and on the inference of domain content in ancestral genes and gene content in ancestral species, compared to existing approaches.