title: Reconstruction of ancestral metabolic enzymes reveals molecular mechanisms underlying evolutionary innovation through gene duplication.
abstract: Gene duplications are believed to facilitate evolutionary innovation. However, the mechanisms shaping the fate of duplicated genes remain heavily debated because the molecular processes and evolutionary forces involved are difficult to reconstruct. Here, we study a large family of fungal glucosidase genes that underwent several duplication events. We reconstruct all key ancestral enzymes and show that the very first preduplication enzyme was primarily active on maltose-like substrates, with trace activity for isomaltose-like sugars. Structural analysis and activity measurements on resurrected and present-day enzymes suggest that both activities cannot be fully optimized in a single enzyme. However, gene duplications repeatedly spawned daughter genes in which mutations optimized either isomaltase or maltase activity. Interestingly, similar shifts in enzyme activity were reached multiple times via different evolutionary routes. Together, our results provide a detailed picture of the molecular mechanisms that drove divergence of these duplicated enzymes and show that whereas the classic models of dosage, sub-, and neofunctionalization are helpful to conceptualize the implications of gene duplication, the three mechanisms co-occur and intertwine.
authors.affiliation: VIB Laboratory for Systems Biology, Leuven, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Voordeckers
authors.forename: Chris A
authors.initials: CA
authors.lastname: Brown
authors.forename: Kevin
authors.initials: K
authors.lastname: Vanneste
authors.forename: Elisa
authors.initials: E
authors.lastname: van der Zande
authors.forename: Arnout
authors.initials: A
authors.lastname: Voet
authors.forename: Steven
authors.initials: S
authors.lastname: Maere
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Verstrepen
mesh_terms: D000596:Amino Acids / Q000235:genetics; D001665:Binding Sites; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000235:genetics; D018628:Gene Dosage / Q000187:drug effects; D020440:Gene Duplication / Q000187:drug effects; D020131:Genes, Duplicate / Q000235:genetics; D005960:Glucosides / Q000494:pharmacology; D006868:Hydrolysis / Q000187:drug effects; D008320:Maltose / Q000378:metabolism; D008958:Models, Molecular; D005810:Multigene Family / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development; D012641:Selection, Genetic; D013379:Substrate Specificity / Q000187:drug effects; D000520:alpha-Glucosidases / Q000235:genetics*
chemical_list: D000596:Amino Acids; D005656:Fungal Proteins; D005960:Glucosides; D008320:Maltose; D000520:alpha-Glucosidases