Collateral toxicity limits the evolution of bacterial Release Factor 2 towards total omnipotence

Abdalaal, HindUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Joakim Näsvall (author)

The two first authors contributed equally to this work.
When new genes evolve through modification of existing genes, there are often trade-offs between the new and original functions, making gene duplication and amplification necessary to buffer deleterious effects on the original function. We have used experimental evolution of a bacterial strain lacking peptide release factor 1 (RF1) in order to study how peptide release factor 2 (RF2) evolves to compensate the loss of RF1. As expected, amplification of the RF2-encoding gene prfB to high copy number was a rapid initial response, followed by the appearance of mutations in RF2 and other components of the translation machinery. Characterization of the evolved RF2 variants by their effects on bacterial growth rate, reporter gene expression, and in vitro translation termination reveals a complex picture of reduced discrimination between the cognate and near cognate stop codons and highlight a functional trade-off that we term “collateral toxicity”. We suggest that this type of trade-off may be a more serious obstacle in new gene evolution than the more commonly discussed evolutionary trade-offs between “old” and “new” functions of a gene, as it cannot be overcome by gene copy number changes. Further, we suggest a model for how RF2 autoregulation responds not only to alterations in the demand for RF2 activity, but also for RF1 activity.

Pundir, ShreyaUppsala universitet,Institutionen för cell- och molekylärbiologi,Suparna Sanyal(Swepub:uu)shrpu756 (author)
Ge, XueliangUppsala universitet,Molekylärbiologi,Suparna Sanyal(Swepub:uu)xuege734 (author)
Sanyal, SuparnaUppsala universitet,Molekylärbiologi,Suparna Sanyal(Swepub:uu)sucsa102 (author)
Näsvall, JoakimUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Joakim Näsvall(Swepub:uu)joana125 (author)
Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)

In:Molecular biology and evolution: Oxford University Press (OUP)37:10, s. 2918-29300737-40381537-1719

By the author/editor: Abdalaal, Hind; Pundir, Shreya; Ge, Xueliang; Sanyal, Suparna; Näsvall, Joakim

About the subject

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Microbiology

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