Between compensatory mutations and synthetic lethals: genetic mutations, a new challenge for tomorrow's medicine

Claude Bazin (1) , Rémi Coupaye (1) , Sandrine Middendorp (1) , Anne Vanet (2)

1 IJM (UMR_7592) - Institut Jacques Monod
2 Atelier de Bio Informatique

In the macromolecular world, the evolution of two building blocks (two nucleotides or two amino acids) can be interdependent in various ways, including: (i) a mutation at one site compensates a deleterious mutation at another site or (ii) mutations at two different sites are lethal only when they co-occur in the same genome. These two situations are known as “compensatory mutations” and “synthetic lethals,” respectively. Although the first category has been studied extensively, especially since the 1970s—a period of time during which prokaryotic genetics grew by leaps and bounds—the second remained unstudied until the late 1990s. Studies on yeast first placed synthetic lethals at the forefront; at the beginning of the new century, therapies against cancers relied on such relationships. Finally, in recent years, synthetic lethals were used to develop stable therapies against RNA viruses, and these studies revealed a promising method for developing vaccines against these viruses. Here, we review the current understanding of these two situations and the implications of both compensatory mutations and synthetic lethals for the elucidation of biological pathways, cancer research, evolution, and gene expression.

Mots clés: covariation; compensatory mutations; synthetic lethals; drug targets; RNA viruses

Domaines: Génétique

Claude Bazin, Rémi Coupaye, Sandrine Middendorp, Anne Vanet. Between compensatory mutations and synthetic lethals: genetic mutations, a new challenge for tomorrow's medicine. Science Postprint, 2014, 1 (1), pp.e00035. ⟨10.14340/spp.2014.10r0002⟩. ⟨hal-01898724⟩