Different Aneuploidies Arise From the Same Bridge-Induced Chromosomal Translocation Event in Saccharomyces cerevisiae

Abstract

Chromosome translocations are gross chromosomal rearrangements that have often been associated with cancer development in mammalian cells. The feasibility of drastically reshaping the genome with a single translocation event also gives this molecular event a powerful capacity to drive evolution. Despite these implications and their role in genome instability, very little is known about the molecular mechanisms that promote and accompany these events. Here, at the molecular level, we describe 10 morphologically and physiologically different translocants ensuing from the induction of the same bridge-induced translocation (BIT) event in the budding yeast Saccharomyces cerevisiae. We have demonstrated that, despite their common origin from the integration of the same linear DNA construct, all 10 translocation mutant strains have different phenotypes and the ability to sporulate and regulate gene expression and morphology. We also provide insights into how heterogeneous phenotypic variations originate from the same initial genomic event. Here we show eight different ways in which yeast cells have dealt with a single initial event inducing translocation. Our results are in agreement with the formation of complex rearrangements and abnormal karyotypes described in many leukemia patients, thus confirming the modellistic value of the yeast BIT system for mammalian cells.