title: Detecting functional divergence after gene duplication through evolutionary changes in posttranslational regulatory sequences.
abstract: Gene duplication is an important evolutionary mechanism that can result in functional divergence in paralogs due to neo-functionalization or sub-functionalization. Consistent with functional divergence after gene duplication, recent studies have shown accelerated evolution in retained paralogs. However, little is known in general about the impact of this accelerated evolution on the molecular functions of retained paralogs. For example, do new functions typically involve changes in enzymatic activities, or changes in protein regulation? Here we study the evolution of posttranslational regulation by examining the evolution of important regulatory sequences (short linear motifs) in retained duplicates created by the whole-genome duplication in budding yeast. To do so, we identified short linear motifs whose evolutionary constraint has relaxed after gene duplication with a likelihood-ratio test that can account for heterogeneity in the evolutionary process by using a non-central chi-squared null distribution. We find that short linear motifs are more likely to show changes in evolutionary constraints in retained duplicates compared to single-copy genes. We examine changes in constraints on known regulatory sequences and show that for the Rck1/Rck2, Fkh1/Fkh2, Ace2/Swi5 paralogs, they are associated with previously characterized differences in posttranslational regulation. Finally, we experimentally confirm our prediction that for the Ace2/Swi5 paralogs, Cbk1 regulated localization was lost along the lineage leading to SWI5 after gene duplication. Our analysis suggests that changes in posttranslational regulation mediated by short regulatory motifs systematically contribute to functional divergence after gene duplication.
authors.affiliation: Department of Cell & Systems Biology, University of Toronto, Toronto, Canada; Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Canada.
authors.forename: Alex N
authors.initials: AN
authors.lastname: Nguyen Ba
authors.affiliation: Department of Cell & Systems Biology, University of Toronto, Toronto, Canada.
authors.forename: Bob
authors.initials: B
authors.lastname: Strome
authors.affiliation: Department of Cell & Systems Biology, University of Toronto, Toronto, Canada.
authors.forename: Jun Jie
authors.initials: JJ
authors.lastname: Hua
authors.affiliation: Department of Cell & Systems Biology, University of Toronto, Toronto, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Desmond
authors.affiliation: Département de Biologie, IBIS and PROTEO, Pavillon Charles-Eugene-Marchand, Laval University, Québec City, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gagnon-Arsenault
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Weiss
authors.affiliation: Département de Biologie, IBIS and PROTEO, Pavillon Charles-Eugene-Marchand, Laval University, Québec City, Canada.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Landry
authors.affiliation: Department of Cell & Systems Biology, University of Toronto, Toronto, Canada; Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Canada.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Moses
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D019295:Computational Biology; D003198:Computer Simulation; D019143:Evolution, Molecular; D020440:Gene Duplication / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D004718:Saccharomycetales / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA