Spore-autonomous fluorescent protein expression identifies meiotic chromosome mis-segregation as the principal cause of hybrid sterility in yeast

Abstract

Genome-wide sequence divergence between populations can cause hybrid sterility through the action of the anti-recombination system, which rejects crossover repair of double strand breaks between nonidentical sequences. Because crossovers are necessary to ensure proper segregation of homologous chromosomes during meiosis, the reduced recombination rate in hybrids can result in high levels of nondisjunction and therefore low gamete viability. Hybrid sterility in interspecific crosses of Saccharomyces yeasts is known to be associated with such segregation errors, but estimates of the importance of nondisjunction to postzygotic reproductive isolation have been hampered by difficulties in accurately measuring nondisjunction frequencies. Here, we use spore-autonomous fluorescent protein expression to quantify nondisjunction in both interspecific and intraspecific yeast hybrids. We show that segregation is near random in interspecific hybrids. The observed rates of nondisjunction can explain most of the sterility observed in interspecific hybrids through the failure of gametes to inherit at least one copy of each chromosome. Partially impairing the anti-recombination system by preventing expression of the RecQ helicase SGS1 during meiosis cuts nondisjunction frequencies in half. We further show that chromosome loss through nondisjunction can explain nearly all of the sterility observed in hybrids formed between two populations of a single species. The rate of meiotic nondisjunction of each homologous pair was negatively correlated with chromosome size in these intraspecific hybrids. Our results demonstrate that sequence divergence is not only associated with the sterility of hybrids formed between distantly related species but may also be a direct cause of reproductive isolation in incipient species.

Aneuploidy in yeast: Segregation error or adaptation mechanism?

“…Interestingly, the pattern of decreasing aneuploidy rates as chromosome size increases (Figure 4) has been reported in meiotic products of intraspecific S. paradoxus × S. paradoxus hybrids made from divergent strains (N17 × N44; Rogers et al, 2018). This was not observed in meiotic products of interspecific S. cerevisiae × S. paradoxus hybrids (Rogers et al, 2018). To uncover the exact mechanism behind this discrepancy will require further experimentation.…”

“…There is no data to date on the long‐term benefits or costs of aneuploidy through hybrid meiosis. However, we think this is a fruitful field for further research, given (a) the accumulating evidence for adaptation through aneuploidy (Selmecki et al, ; Yona et al, ), (b) the evidence that hybrid meiosis leads to high rates of aneuploidy in yeast (Rogers et al, ), and (c) the circumstance that both aneuploidy and hybridisation occur in stressful and perturbed habitats (Garroway et al, ; Muhlfeld et al, ). Whether hybridisation will generally assist or hamper adaptation to changing environments, with or without aneuploidy, is itself a debated topic (Hamilton & Miller, ; Kovach, Luikart, Lowe, Boyer, & Muhlfeld, ; Miller & Hamilton, ).…”

“…Rogers et al recently showed that of ~15,000 F1 hybrid tetrads studied, more than a third exhibited nondisjunction. Spores carried at least one aneuploidy (40.3% per chromosome across all spores) with between one and five chromosomes affected per spore (Rogers et al, ). The underlying molecular mechanism causing infertility between species is most likely antirecombination, where a lack of recombination caused by the mismatch repair (MMR) system causes missegregation of homeologous chromosomes during interspecific hybrid meiosis (Chambers, Hunter, Louis, & Borts, ; Greig, ; Hunter, Chambers, Louis, & Borts, ; Kao et al, ).…”

“…To uncover the exact mechanism behind this discrepancy will require further experimentation. If we were to speculate, as the number of crossovers in S. cerevisiae directly scales with chromosome size (Mancera, Bourgon, Brozzi, Huber, & Steinmetz, ), this could explain why smaller chromosomes are more likely to become aneuploid in intraspecific hybrids (Rogers et al, ). However, this does not explain why the pattern is absent in interspecific hybrids.…”

“…We think it is important and timely that we start exploring the connection between hybridisation, aneuploidy, and adaptation in microbes. Chromosomal nondisjunction is known to be a particularly prevalent outcome of interspecific hybrid meiosis in yeast, leaving a large fraction of the F1 hybrids offspring (spores) aneuploid (Boynton, Janzen, & Greig, 2018;Greig, Travisano, Louis, & Borts, 2003;Rogers, McConnell, Ono, & Greig, 2018). Aneuploidy is thus thought to be one of the main reasons for F1 hybrid sterility in yeast, causing almost complete reproductive isolation between species of the Saccharomyces sensu stricto complex (F1 hybrids produce less than 1% viable gametes (Hou, Friedrich, de Montigny, & Schacherer, 2014;Liti, Barton, & Louis, 2006).…”