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PLoS One. 2012;7(7):e40125. doi: 10.1371/journal.pone.0040125. Epub 2012 Jul 13.

Moonlighting peptides with emerging function.

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Biochemistry and Structural Biology Department, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México DF, México.

Erratum in

  • PLoS One. 2013;8(10). doi:10.1371/annotation/fc687f18-ce8e-4704-87a5-d6807953204e.


Hunter-killer peptides combine two activities in a single polypeptide that work in an independent fashion like many other multi-functional, multi-domain proteins. We hypothesize that emergent functions may result from the combination of two or more activities in a single protein domain and that could be a mechanism selected in nature to form moonlighting proteins. We designed moonlighting peptides using the two mechanisms proposed to be involved in the evolution of such molecules (i.e., to mutate non-functional residues and the use of natively unfolded peptides). We observed that our moonlighting peptides exhibited two activities that together rendered a new function that induces cell death in yeast. Thus, we propose that moonlighting in proteins promotes emergent properties providing a further level of complexity in living organisms so far unappreciated.

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