A utilização reguladora da redundância genética através de circuitos de backup responsivos

quarta-feira, setembro 05, 2012

The regulatory utilization of genetic redundancy through responsive backup circuits

Ran Kafri *, Melissa Levy *, and Yitzhak Pilpel †

Author Affiliations

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel

Communicated by Marc W. Kirschner, Harvard Medical School, Boston, MA, June 12, 2006

↵*R.K. and M.L. contributed equally to this work. (received for review March 6, 2006)


Functional redundancies, generated by gene duplications, are highly widespread throughout all known genomes. One consequence of these redundancies is a tremendous increase to the robustness of organisms to mutations and other stresses. Yet, this very robustness also renders redundancy evolutionarily unstable, and it is, thus, predicted to have only a transient lifetime. In contrast, numerous reports describe instances of functional overlaps that have been conserved throughout extended evolutionary periods. More interestingly, many such backed-up genes were shown to be transcriptionally responsive to the intactness of their redundant partner and are up-regulated if the latter is mutationally inactivated. By manual inspection of the literature, we have compiled a list of such “responsive backup circuits” in a diverse list of species. Reviewing these responsive backup circuits, we extract recurring principles characterizing their regulation. We then apply modeling approaches to explore further their dynamic properties. Our results demonstrate that responsive backup circuits may function as ideal devices for filtering nongenetic noise from transcriptional pathways and obtaining regulatory precision. We thus challenge the view that such redundancies are simply leftovers of ancient duplications and suggest they are an additional component to the sophisticated machinery of cellular regulation. In this respect, we suggest that compensation for gene loss is merely a side effect of sophisticated design principles using functional redundancy.

evolution gene duplications modeling systems biology noise



Alguém me belisque: Design principles? Foi isso mesmo que eu li no abstract???