Per aspera ad astra : When harmful chromosomal translocations become a plus value in genetic evolution. Lessons from Saccharomyces cerevisiae

In this review we will focus on chromosomal translocations (either spontaneous or induced) in budding yeast. Indeed, very few organisms toler- ate so well aneuploidy like Saccharomyces , allowing in depth studies on chromosomal numerical aberrations. Many wild type strains naturally devel- op chromosomal rearrangements while adapting to different environmental conditions. Translocations, in particular, are valuable not only because they naturally drive species evolution, but because they might allow the artificial generation of new strains that can be optimized for industrial purposes. In this area, several methodologies to artificially trigger chromosomal transloca- tions have been conceived in the past years, such as the chromosomal frag- mentation vector (CFV) technique, the Cre-loxP procedure, the FLP/FRT re- combination method and, recently, the bridge - induced translocation (BIT) system. An overview of the methodologies to generate chromosomal translo- cations in yeast will be presented and discussed considering advantages and drawbacks of each technology, focusing in particular on the recent BIT sys- tem. Translocants are important for clinical studies because translocated yeast cells resemble cancer cells from morphological and physiological points of view and because the translocation event ensues in a transcriptional de- regulation with a subsequent multi-factorial genetic adaptation to new, selec- tive environmental conditions. The phenomenon of post-translocational ad- aptation (PTA) is discussed, providing some new unpublished data and pro- posing the hypothesis that translocations may drive evolution through adap-