title: The duplicated deacetylases Sir2 and Hst1 subfunctionalized by acquiring complementary inactivating mutations.
abstract: Protein families are generated by successive rounds of gene duplication and subsequent diversification. However, the paths by which duplicated genes acquire distinct functions are not well characterized. We focused on a pair of duplicated deacetylases from Saccharomyces cerevisiae, Sir2 and Hst1, that subfunctionalized after duplication. As a proxy for the ancestral, nonduplicated deacetylase, we studied Sir2 from another yeast, Kluyveromyces lactis. We compared the interaction domains of these deacetylases for the Sir transcriptional silencing complex, which acts with ScSir2, and the Sum1 repressor, which acts with ScHst1, and found that these interaction domains have been retained over the course of evolution and can be disrupted by simple amino acid substitutions. Therefore, Sir2 and Hst1 subfunctionalized by acquiring complementary inactivating mutations in these interaction domains.
authors.affiliation: Department of Biochemistry, Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Cara A
authors.initials: CA
authors.lastname: Froyd
authors.forename: Laura N
authors.initials: LN
authors.lastname: Rusche
mesh_terms: D019143:Evolution, Molecular; D007716:Kluyveromyces / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000502:physiology; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D056565:Sirtuin 2 / Q000235:genetics* / Q000502:physiology
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C103934:HST1 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2