Aneuploidy can be an evolutionary detour on the path to genetic adaptation

Aneuploidy is common in eukaryotes, often leading to decreased growth and fitness. However, evidence from yeast and fungi, as well as human tumour cells, suggests that specific aneuploidies can be beneficial under stressful conditions and facilitate adaptation. Yona et al. (2012) have demonstrated in an evolutionary experiment with yeast that populations evolving under heat stress become aneuploid, only to later revert back to euploidy after genetic mutations have accumulated. It has therefore been suggested that aneuploidy serves as a "stepping stone" on the path to adaptation.

To test this hypothesis, we developed an evolutionary model with both aneuploidy and mutation, and fit it to the results of the experiment using a Bayesian inference framework. We then predicted the genotype frequency dynamics during the experiment, demonstrating that the majority of the evolved euploid population likely did not descend from aneuploid cells, but rather directly from the euploid wild-type population. Surprisingly, this agrees with DNA sequencing results in which mutant alleles that were common in aneuploid cells were uncommon in the evolved euploid population, and vice-versa. Our model further predicts that if the experiment was repeated with smaller populations, then a larger fraction of the evolved population would descend from aneuploid cells.

Thus, we suggest that aneuploidy can be an inevitable evolutionary "detour" rather than a "stepping stone": it can delay, rather than facilitate, the adaptation of the population, and cells that become aneuploid may leave less descendants compared to cells that remain diploid.