Wine yeast strains show a high level of chromosome length polymorphism. This polymorphism is mainly generated by illegitimate recombination mediated by Ty transposons or subtelomeric repeated sequences. We have found, however, that the SSU1-R allele, which confers sulfite resistance to yeast cells, is the product of a reciprocal translocation between chromosomes VIII and XVI due to unequal crossing-over mediated by microhomology between very short sequences on the 5Ј upstream regions of the SSU1 and ECM34 genes. We also show that this translocation is only present in wine yeast strains, suggesting that the use for millennia of sulfite as a preservative in wine production could have favored its selection. This is the first time that a gross chromosomal rearrangement is shown to be involved in the adaptive evolution of Saccharomyces cerevisiae.[The sequence data from this study have been submitted to EMBL under accession nos. AF239757, AF239758, and AJ458340-AJ458367. The following individual kindly provided reagents, samples, or unpublished information as indicated in the paper: N. Goto-Yamamoto.] The unaware use of yeast for winemaking by the first agricultural civilizations has been reported as far back as 7400 years ago. Until the middle of the last millennium, wines were mainly produced around the Mediterranean Sea and the Caucasus. Since then, winemaking has spread with the European colonizers throughout the temperate regions of the world (Pretorius 2000).Although different genera and species of yeasts are found in musts, the species Saccharomyces cerevisiae is mainly responsible for the transformation of musts into wines. The origin of S. cerevisiae is controversial. Some authors propose that this species is a "natural" organism present in plant fruits (Mortimer and Polsinelli 1999). Others argue that S. cerevisiae is a domesticated species originated from its closest relative S. paradoxus, a wild species found all around the world (Vaughan-Martini and Martini 1995). This debate is important in postulating the original genome of S. cerevisiae and how the strong selective pressure applied since its first unconscious use in controlled fermentation processes has reshaped it. Useful phenotypic traits such as fast growth in sugar-rich media, high alcohol production and tolerance, and good flavor production selected for billions of generations have had strong influences on the S. cerevisiae genome.In contrast to most S. cerevisiae strains used in the laboratory, which are either haploid or diploid and have a constant chromosome electrophoretic profile, wine yeast strains are mainly diploid, aneuploid, or polyploid, homothallic, and . Their exacerbated capacity to reorganize its genome by chromosome rearrangements such as Ty-promoted chromosomal translocations (Longo and Vézinhet 1993;Rachidi et al. 1999), mitotic crossing-over (Aguilera et al. 2000), and gene conversion (Puig et al. 2000) promotes a faster adaptation to environmental changes than spontaneous mutations, which occur at comparatively very low rat...