Hybrids between species are usually unviable or sterile. One possible mechanism causing reproductive isolation is incompatibility between genes from different species. These "speciation" genes are interacting components that cannot function properly when mixed with alleles from other species. To test whether such genes exist in two closely related yeast species, we constructed hybrid lines in which one or two chromosomes were derived from Saccharomyces bayanus, and the rest were from Saccharomyces cerevisiae. We found that the hybrid line with Chromosome 13 substitution was completely sterile and identified Aep2, a mitochondrial protein encoded on Chromosome 13, to cause the sporulation defect as S. bayanus AEP2 is incompatible with S. cerevisiae mitochondria. This is caused by the inability of S. bayanus Aep2 protein to regulate the translation of the S. cerevisiae OLI1 mRNA. We speculate that AEP2 and OLI1 have evolved during the adaptation of S. bayanus to nonfermentable carbon sources, thereby driving speciation.

The hop2 mutant of S. cerevisiae displays a novel phenotype: meiotic chromosomes form nearly wild-type amounts of synaptonemal complex, but most chromosomes are engaged in synapsis with nonhomologous partners. The meiosis-specific Hop2 protein localizes to chromosomes prior to and during synapsis and in the absence of the double-strand breaks that initiate recombination. hop2 strains sustain a wild-type level of meiotic double-strand breaks, but these breaks remain unrepaired. The hop2 mutant arrests at the pachytene stage of meiotic prophase with the RecA-like protein Dmc1 located at numerous sites along synapsed chromosomes. We propose that the Hop2 protein functions to prevent synapsis between nonhomologous chromosomes.

Incompatibility between nuclear and mitochondrial genomes in yeast species may represent a general mechanism of reproductive isolation during yeast evolution.

The authors propose that short repeat sequences may play an important role in causing the pervasive clustering of mutations across diverse genomes from prokaryotes to humans.

Large-scale genome rearrangements have been observed in cells adapting to various selective conditions during laboratory evolution experiments. However, it remains unclear whether these types of mutations can be stably maintained in populations and how they impact the evolutionary trajectories. Here we show that chromosomal rearrangements contribute to extremely high copper tolerance in a set of natural yeast strains isolated from Evolution Canyon (EC), Israel. The chromosomal rearrangements in EC strains result in segmental duplications in chromosomes 7 and 8, which increase the copy number of genes involved in copper regulation, including the crucial transcriptional activator CUP2 and the metallothionein CUP1. The copy number of CUP2 is correlated with the level of copper tolerance, indicating that increasing dosages of a single transcriptional activator by chromosomal rearrangements has a profound effect on a regulatory pathway. By gene expression analysis and functional assays, we identified three previously unknown downstream targets of CUP2: PHO84, SCM4, and CIN2, all of which contributed to copper tolerance in EC strains. Finally, we conducted an evolution experiment to examine how cells maintained these changes in a fluctuating environment. Interestingly, the rearranged chromosomes were reverted back to the wild-type configuration at a high frequency and the recovered chromosome became fixed in less selective conditions. Our results suggest that transposon-mediated chromosomal rearrangements can be highly dynamic and can serve as a reversible mechanism during early stages of adaptive evolution.