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dc.contributor.authorHobbs, Joanne K.
dc.contributor.authorPrentice, Erica J.
dc.contributor.authorGroussin, Mathieu
dc.contributor.authorArcus, Vickery L.
dc.date.accessioned2016-10-27T21:46:22Z
dc.date.available2016-10-27T21:46:22Z
dc.date.issued2015-09
dc.date.submitted2015-06
dc.identifier.issn0022-2844
dc.identifier.issn1432-1432
dc.identifier.urihttp://hdl.handle.net/1721.1/105120
dc.description.abstractAncestral 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 ΔleuB 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.en_US
dc.description.sponsorshipFrance. Agence nationale de la rechercheen_US
dc.publisherSpringer USen_US
dc.relation.isversionofhttp://dx.doi.org/10.1007/s00239-015-9697-5en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceSpringer USen_US
dc.titleReconstructed Ancestral Enzymes Impose a Fitness Cost upon Modern Bacteria Despite Exhibiting Favourable Biochemical Propertiesen_US
dc.typeArticleen_US
dc.identifier.citationHobbs, Joanne K. et al. “Reconstructed Ancestral Enzymes Impose a Fitness Cost upon Modern Bacteria Despite Exhibiting Favourable Biochemical Properties.” Journal of Molecular Evolution 81.3–4 (2015): 110–120.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.mitauthorGroussin, Mathieu
dc.relation.journalJournal of Molecular Evolutionen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2016-08-18T15:41:06Z
dc.language.rfc3066en
dc.rights.holderSpringer Science+Business Media New York
dspace.orderedauthorsHobbs, Joanne K.; Prentice, Erica J.; Groussin, Mathieu; Arcus, Vickery L.en_US
dspace.embargo.termsNen
dc.identifier.orcidhttps://orcid.org/0000-0002-0942-7217
mit.licensePUBLISHER_POLICYen_US


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