title: Preservation of genetic and regulatory robustness in ancient gene duplicates of Saccharomyces cerevisiae.
abstract: Biological systems remain robust against certain genetic and environmental challenges. Robustness allows the exploration of ecological adaptations. It is unclear what factors contribute to increasing robustness. Gene duplication has been considered to increase genetic robustness through functional redundancy, accelerating the evolution of novel functions. However, recent findings have questioned the link between duplication and robustness. In particular, it remains elusive whether ancient duplicates still bear potential for innovation through preserved redundancy and robustness. Here we have investigated this question by evolving the yeast Saccharomyces cerevisiae for 2200 generations under conditions allowing the accumulation of deleterious mutations, and we put mechanisms of mutational robustness to a test. S. cerevisiae declined in fitness along the evolution experiment, but this decline decelerated in later passages, suggesting functional compensation of mutated genes. We resequenced 28 genomes from experimentally evolved S. cerevisiae lines and found more mutations in duplicates--mainly small-scale duplicates--than in singletons. Genetically interacting duplicates evolved similarly and fixed more amino acid-replacing mutations than expected. Regulatory robustness of the duplicates was supported by a larger enrichment for mutations at the promoters of duplicates than at those of singletons. Analyses of yeast gene expression conditions showed a larger variation in the duplicates' expression than that of singletons under a range of stress conditions, sparking the idea that regulatory robustness allowed a wider range of phenotypic responses to environmental stresses, hence faster adaptations. Our data support the persistence of genetic and regulatory robustness in ancient duplicates and its role in adaptations to stresses.
authors.affiliation: Department of Genetics, Smurfit Institute of Genetics, School of Genetics and Microbiology, University of Dublin, Trinity College Dublin, Dublin 2, Ireland; Animal and Bioscience Department, Teagasc, Dunsany, County Meath, Ireland;
authors.forename: Orla M
authors.initials: OM
authors.lastname: Keane
authors.affiliation: Department of Genetics, University of Valencia, 46100 Valencia, Spain; Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de los Alimentos (CSIC), 46100 Valencia, Spain;
authors.forename: Christina
authors.initials: C
authors.lastname: Toft
authors.affiliation: Department of Biological Sciences, University at Buffalo, Buffalo, New York 14260, USA;
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Carretero-Paulet
authors.affiliation: Department of Biology, National University of Ireland, Maynooth, County Kildare, Ireland;
authors.forename: Gary W
authors.initials: GW
authors.lastname: Jones
authors.affiliation: Department of Genetics, Smurfit Institute of Genetics, School of Genetics and Microbiology, University of Dublin, Trinity College Dublin, Dublin 2, Ireland; Integrative and Systems Biology Group, Department of Abiotic Stress, Instituto de Biología Molecular y Celular de Plantas (CSIC-UPV), 46022 Valencia, Spain mfares@ibmcp.upv.es.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Fares
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000465:Algorithms; D015825:Chromosomes, Fungal / Q000235:genetics; D004252:DNA Mutational Analysis; D019020:Directed Molecular Evolution; D020440:Gene Duplication; D005800:Genes, Fungal / Q000235:genetics; D016681:Genome, Fungal / Q000235:genetics; D054643:INDEL Mutation; D008957:Models, Genetic; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics