Proteotoxicity caused by perturbed protein complexes underlies hybrid incompatibility in yeast.

Dobzhansky-Muller incompatibilities represent a major driver of reproductive isolation between species. They are caused when interacting components encoded by alleles from different species cannot function properly when mixed. At incipient stages of speciation, complex incompatibilities involving multiple genetic loci with weak effects are frequently observed, but the underlying mechanisms remain elusive. Here we show perturbed proteostasis leading to compromised mitosis and meiosis in Saccharomyces cerevisiae hybrid lines carrying one or two chromosomes from Saccharomyces bayanus var. uvarum. Levels of proteotoxicity are correlated with the number of protein complexes on replaced chromosomes. Proteomic approaches reveal that multi-protein complexes with subunits encoded by replaced chromosomes tend to be unstable. Furthermore, hybrid defects can be alleviated or aggravated, respectively, by up- or down-regulating the ubiquitin-proteasomal degradation machinery, suggesting that destabilized complex subunits overburden the proteostasis machinery and compromise hybrid fitness. Our findings reveal the general role of impaired protein complex assembly in complex incompatibilities.

Genome plasticity in Paramecium bursaria revealed by population genomics.

BACKGROUND: Ciliates are an ancient and diverse eukaryotic group found in various environments. A unique feature of ciliates is their nuclear dimorphism, by which two types of nuclei, the diploid germline micronucleus (MIC) and polyploidy somatic macronucleus (MAC), are present in the same cytoplasm and serve different functions. During each sexual cycle, ciliates develop a new macronucleus in which newly fused genomes are extensively rearranged to generate functional minichromosomes. Interestingly, each ciliate species seems to have its way of processing genomes, providing a diversity of resources for studying genome plasticity and its regulation. Here, we sequenced and analyzed the macronuclear genome of different strains of Paramecium bursaria, a highly divergent species of the genus Paramecium which can stably establish endosymbioses with green algae. RESULTS: We assembled a high-quality macronuclear genome of P. bursaria and further refined genome annotation by comparing population genomic data. We identified several species-specific expansions in protein families and gene lineages that are potentially associated with endosymbiosis. Moreover, we observed an intensive chromosome breakage pattern that occurred during or shortly after sexual reproduction and contributed to highly variable gene dosage throughout the genome. However, patterns of copy number variation were highly correlated among genetically divergent strains, suggesting that copy number is adjusted by some regulatory mechanisms or natural selection. Further analysis showed that genes with low copy number variation among populations tended to function in basic cellular pathways, whereas highly variable genes were enriched in environmental response pathways. CONCLUSIONS: We report programmed DNA rearrangements in the P. bursaria macronuclear genome that allow cells to adjust gene copy number globally according to individual gene functions. Our results suggest that large-scale gene copy number variation may represent an ancient mechanism for cells to adapt to different environments.