Reconstruction of Ancestral Metabolic Enzymes Reveals Molecular Mechanisms Underlying Evolutionary Innovation through Gene Duplication

Voordeckers, Karin; Brown, Chris A.; Vanneste, Kevin; Zande, Elisa van der; Voet, Arnout; Maere, Steven; Verstrepen, Kevin J.

doi:10.1371/journal.pbio.1001446

Cited by 178 publications

(242 citation statements)

References 70 publications

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“…Another interesting example is the evolution of the MALS family of a-glucosidases in S. cerevisiae and its close relatives (Voordeckers et al 2012). S. cerevisiae has seven closely related a-glucosidases (MAL12 and 32, IMA1 -5) with different substrate specificities.…”

Section: Predictions From and Supporting Evidence For The Iad Modelmentioning

confidence: 99%

Evolution of New Functions De Novo and from Preexisting Genes

Andersson

Jerlström-Hultqvist

Näsvall

2015

Cold Spring Harb Perspect Biol

133

107

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Section: Predictions From and Supporting Evidence For The Iad Modelmentioning

confidence: 99%

Evolution of New Functions De Novo and from Preexisting Genes

Andersson

Jerlström-Hultqvist

Näsvall

2015

Cold Spring Harb Perspect Biol

133

107

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“…ASR uses a combination of phylogenetics, evolutionary theory, synthetic biology and protein biochemistry to infer the sequences of ancestral proteins and then characterise them in the laboratory. It has provided otherwise unobtainable insight into many evolutionary questions, such as ligand specificity in steroid hormone receptors (Bridgham et al 2006(Bridgham et al , 2009Eick et al 2012), spectral tuning in visual pigments (Chang et al 2002;Chinen et al 2005;Yokoyama et al 2008) and substrate specificity amongst fungal a-glucosidases (Voordeckers et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Reconstructed Ancestral Enzymes Impose a Fitness Cost upon Modern Bacteria Despite Exhibiting Favourable Biochemical Properties

et al. 2015

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Ancestral sequence reconstruction has been widely used to study historical enzyme evolution, both from biochemical and cellular perspectives. Two properties of reconstructed ancestral proteins/enzymes are commonly reported-high thermostability and high catalytic activity-compared with their contemporaries. Increased protein stability is associated with lower aggregation rates, higher soluble protein abundance and a greater capacity to evolve, and therefore, these proteins could be considered ''superior'' to their contemporary counterparts. In this study, we investigate the relationship between the favourable in vitro biochemical properties of reconstructed ancestral enzymes and the organismal fitness they confer in vivo. We have previously reconstructed several ancestors of the enzyme LeuB, which is essential for leucine biosynthesis. Our initial fitness experiments revealed that overexpression of ANC4, a reconstructed LeuB that exhibits high stability and activity, was only able to partially rescue the growth of a DleuB strain, and that a strain complemented with this enzyme was outcompeted by strains carrying one of its descendants. When we expanded our study to include five reconstructed LeuBs and one contemporary, we found that neither in vitro protein stability nor the catalytic rate was correlated with fitness. Instead, fitness showed a strong, negative correlation with estimated evolutionary age (based on phylogenetic relationships). Our findings suggest that, for reconstructed ancestral enzymes, superior in vitro properties do not translate into organismal fitness in vivo. The molecular basis of the relationship between fitness and the inferred age of ancestral LeuB enzymes is unknown, but may be related to the reconstruction process. We also hypothesise that the ancestral enzymes may be incompatible with the other, contemporary enzymes of the metabolic network.

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“…high-affinity sulfate transporter (SUL1) acts as a gene dosage, and the yeast a-glucosidase gene MALS family exhibits aspects of three classical models, such as gene dosage, neo-, and subfunctionalization (Perry et al 2007;Gresham et al 2008;Warringer et al 2011;Voordeckers et al 2012). This study clearly indicates that the copy number amplification of FLO11D also contributes to adaptation in a gene-dosage-dependent manner.…”

Section: Implications Of Flo11d Copy Number Amplificationmentioning

confidence: 91%

“…In humans, most CNVs overlapping genes are under purifying (negative) selection (Conrad et al 2010), but a handful of CNVs are thought to be under positive selection (Cooper et al 2007;Hurles et al 2010;Iskow et al 2012) such as AMY1 (Perry et al 2007). In yeast, there are several examples of how the (increased) copy number can provide a direct selective advantage (Gresham et al 2008;Voordeckers et al 2012).In nature, budding yeast exhibits a number of adaptive responses, such as filamentation, invasive growth, flocculation, and biofilm formation, to overcome a deleterious environment (Fidalgo et al 2006). The FLO (flocculation) gene family plays a central role in the mediation of these adaptive responses.…”

mentioning

confidence: 99%

Adaptation of the Osmotolerant Yeast Zygosaccharomyces rouxii to an Osmotic Environment Through Copy Number Amplification of FLO11D

2013

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Copy number variations (CNVs) contribute to the adaptation process in two possible ways. First, they may have a direct role, in which a certain number of copies often provide a selective advantage. Second, CNVs can also indirectly contribute to adaptation because a higher copy number increases the so-called "mutational target size." In this study, we show that the copy number amplification of FLO11D in the osmotolerant yeast Zygosaccharomyces rouxii promotes its further adaptation to a florformative environment, such as osmostress static culture conditions. We demonstrate that a gene, which was identified as FLO11D, is responsible for flor formation and that its expression is induced by osmostress under glucose-free conditions, which confer unique characteristics to Z. rouxii, such as osmostress-dependent flor formation. This organism possesses zero to three copies of FLO11D, and it appears likely that the FLO11D copy number increased in a branch of the Z. rouxii tree. The cellular hydrophobicity correlates with the FLO11D copy number, and the strain with a higher copy number of FLO11D exhibits a fitness advantage compared to a reference strain under osmostress static culture conditions. Our data indicate that the FLO gene-related system in Z. rouxii has evolved remarkably to adapt to osmostress environments.A N organism adapts to adverse environments to survive and produce progeny. Adaptive evolution is the process through which a population becomes better suited to its environment via mutation, selection, and random drift (Bürger 2000;Cressman 2003;Ewens 2004;Nowak and Sigmund 2004). Types of mutations include nucleotide changes (Steiner et al. 2007;Barrick and Lenski 2009), transposition events (Wilke and Adams 1992;Aminetzach et al. 2005), and copy number variations (CNVs), including gene amplifications (duplication) and deletions (Brown et al. 1998;Perry et al. 2007;Gresham et al. 2010). CNVs can have a phenotypic impact and can consequently alter the fitness of an allele through the following mechanisms: (i) changing the coding sequence of a gene (Yamanaka et al. 2009;Schlattl et al. 2011), (ii) creating paralogs that can diverge from each other and take on new or specialized functions (neofunctionalization or subfunctionalization, respectively) (Ohno 1970;Innan and Kondrashov 2010), and (iii) altering the expression level of a gene (gene dosage effect) (Stranger et al. 2007;Yamanaka et al. 2009;Iskow et al. 2012). In humans, most CNVs overlapping genes are under purifying (negative) selection (Conrad et al. 2010), but a handful of CNVs are thought to be under positive selection (Cooper et al. 2007;Hurles et al. 2010;Iskow et al. 2012) such as AMY1 (Perry et al. 2007). In yeast, there are several examples of how the (increased) copy number can provide a direct selective advantage (Gresham et al. 2008;Voordeckers et al. 2012).In nature, budding yeast exhibits a number of adaptive responses, such as filamentation, invasive growth, flocculation, and biofilm formation, to overcome a deleterious enviro...

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Reconstruction of Ancestral Metabolic Enzymes Reveals Molecular Mechanisms Underlying Evolutionary Innovation through Gene Duplication

Abstract: Resurrection of ancient fungal maltase enzymes uncovers the molecular details of how repeated gene duplications allow the evolution of protein variants with different functions.

Cited by 178 publications

References 70 publications

Evolution of New Functions De Novo and from Preexisting Genes

Evolution of New Functions De Novo and from Preexisting Genes

Reconstructed Ancestral Enzymes Impose a Fitness Cost upon Modern Bacteria Despite Exhibiting Favourable Biochemical Properties

Adaptation of the Osmotolerant Yeast Zygosaccharomyces rouxii to an Osmotic Environment Through Copy Number Amplification of FLO11D

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