Correlated duplications and losses in the evolution of palmitoylation writer and eraser families

Stijn Wittouck, Vera van Noort

Protein post-translational modifications (PTMs) change protein properties. Each PTM type is associated with domain families that apply the modification (writers), remove the modification (erasers) and bind to the modified sites (readers) together called toolkit domains. The evolutionary origin and diversification remains largely understudied, except for tyrosine phosphorylation. Protein palmitoylation entails the addition of a palmitoyl fatty acid to a cysteine residue. This PTM functions as a membrane anchor and is involved in a range of cellular processes. One writer family and two erasers families are known for protein palmitoylation. In this work we unravel the evolutionary history of these writer and eraser families. We constructed a high-quality profile hidden Markov model (HMM) of each family, searched for protein family members in fully sequenced genomes and subsequently constructed phylogenetic distributions of the families. We constructed Maximum Likelihood phylogenetic trees and using gene tree rearrangement and tree reconciliation inferred their evolutionary histories in terms of duplication and loss events. We identified lineages where the families expanded or contracted and found that the evolutionary histories of the families are correlated. The results show that the erasers were invented first, before the origin of the eukaryotes. The writers first arose in the eukaryotic ancestor. The writers and erasers show co-expansions in several eukaryotic ancestral lineages. These expansions often seem to be followed by contractions in some or all of the lineages further in evolution. A general pattern of correlated evolution appears between writer and eraser domains. These co-evolution patterns could be used in new methods for interaction prediction based on phylogenies.