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

Valentina Tosato,Carlo Bruschi

doi:10.15698/mic2015.10.230

Abstract

In this review we will focus on chromosomal translocations (either spontaneous or induced) in budding yeast. Indeed, very few organisms tolerate so well aneuploidy like Saccharomyces, allowing in depth studies on chromosomal numerical aberrations. Many wild type strains naturally develop 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 translocations have been conceived in the past years, such as the chromosomal fragmentation vector (CFV) technique, the Cre-loxP procedure, the FLP/FRT recombination method and, recently, the bridge - induced translocation (BIT) system. An overview of the methodologies to generate chromosomal translocations in yeast will be presented and discussed considering advantages and drawbacks of each technology, focusing in particular on the recent BIT system. 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, selective environmental conditions. The phenomenon of post-translocational adaptation (PTA) is discussed, providing some new unpublished data and proposing the hypothesis that translocations may drive evolution through adaptive genetic selection.

Highlights

Adaptive evolution emerges through random genomic mutations that usually reduce and rarely improve the fitness of an organism
Genomic analysis of these new strains revealed that spontaneous gross chromosomal rearrangements and in particular chromosomal translocations were responsible for this transcriptional shift and were due to adaptation to sulfites [1] and to high ethanol concentration [2, 3]
Chromosomal translocations have been triggered via homologous recombination system (HRS) thanks to these endonucleases functioning in yeast and in higher eukaryotes [53, 54, 55], but all these studies are based on the assumption that, after the HO/I-SceI cut, the free ends undergo an extensive process of 5’->3’ DNA degradation until flanking regions of homology are exposed

Summary

Introduction

Adaptive evolution emerges through random genomic mutations that usually reduce and rarely improve the fitness of an organism. In Saccharomyces, the recombination efficiency of FLP allowed the generation of a large number of applications such as a marker recycling system for multiple gene disruption [19] and “sticking” a gene wherever in the yeast genome (STIK = specific targeted integration of kanamycin resistance DNA) without a resident selective marker [20].

Results

Conclusion