Adaptation from standing genetic variation is an important process underlying evolution in natural populations, but we rarely get the opportunity to observe the dynamics of fitness and genomic changes in real time. Here, we used experimental evolution and Pool-Seq to track the phenotypic and genomic changes of genetically diverse asexual populations of the yeast Saccharomyces cerevisiae in four environments with different fitness costs. We found that populations rapidly and in parallel increased in fitness in stressful environments. In contrast, allele frequencies showed a range of trajectories, with some populations fixing all their ancestral variation in <30 generations and others maintaining diversity across hundreds of generations. We detected parallelism at the genomic level (involving genes, pathways, and aneuploidies) within and between environments, with idiosyncratic changes recurring in the environments with higher stress. In particular, we observed a tendency of becoming haploid-like in one environment, whereas the populations of another environment showed low overall parallelism driven by standing genetic variation despite high selective pressure. This work highlights the interplay between standing genetic variation and the influx of de novo mutations in populations adapting to a range of selective pressures with different underlying trait architectures, advancing our understanding of the constraints and drivers of adaptation. 

Comparative genome analyses have suggested East Asia to be the cradle of the domesticated microbe Brewer's yeast (Saccharomyces cerevisiae), used in the food and biotechnology industry worldwide. Here, we provide seven new, high-quality long-read genomes of nondomesticated yeast strains isolated from primeval forests and other natural environments in China and Taiwan. In a comprehensive analysis of our new genome assemblies, along with other long-read Saccharomycetes genomes available, we show that the newly sequenced East Asians trains are amongthe closest living relatives of the ancestors of the global diversity of Brewer's yeast, confirming predictionsmade from short-read genomic data. Three of these strains (termed the East Asian Clade IX Complex here) share a recent ancestry and evolutionary history suggesting an early divergence from other S. cerevisiae strains before the larger radiation of the species, and prior to its domestication. Our genomic analyses reveal that the wild East Asian strains contain elevated levels of structural variations. The new genomic resources provided here contribute to our understanding of the natural diversity of S. cerevisiae, expand the intraspecific genetic variation found in this heavily domesticated microbe, and provide a foundation for understanding its origin and global colonization history.

Adaptation to novel environments can only occur if natural selection has the raw material to act upon. But small, endangered populations are often genetically depleted, and the acquisition of beneficial de novo mutations often takes too long when population face quick and extreme environmental change. An alternative source for new variation is hybridisation and the genomic reshuffling and structural chromosomal changes accompanying it. In this thesis, I use yeast, experimental evolution, and comparative genomics to investigate the impact of different sources of genetic variation in adaptation to stressful environments - standing genetic variation, de novo mutations, and hybridisation.

In Chapter I, I investigate the role of aneuploidy in the adaptation of microbial eukaryotes and the genetic mechanisms causing erroneous chromosome segregation, using a meta-analysis. I found that smaller chromosomes are more often aneuploid and that the frequency of segregation errors during cell division is higher in genomes with higher initial ploidy. I also propose that the co-occurrence of hybridisation and aneuploidy may provide an adaptive advantage in stressful environments.

Traditionally, microbial experimental evolution studies start with clonal populations, relying on adaptation from de novo mutations alone. In the wild, this is an unlikely scenario. In Chapter II, I evolved genetically diverse founder populations for up to 1000 generations in 4 distinct environments and tracked adaptation dynamics at the phenotypic and genomic level. Almost all populations rapidly increased in fitness but the underlying allele frequency changes were surprisingly diverse and environment-specific. While in some populations all ancestral variation went to fixation in < 30 generations, others maintained genetic diversity across hundreds of generations. I found stunning parallelism of de novo mutations at the gene and pathway level and detected potentially adaptive aneuploidies.

Hybridisation drastically boosts the genetic diversity of populations, which can allow for transgressive hybrids (hopeful monsters) with selective advantages in novel environments. In Chapter III, I made hybrid crosses at increasing parental divergence (using divergently evolved populations from Chapter II) and measured how much heterosis and transgressive segregation occurred in F1 and F2 hybrids when exposing them to 50 new, stressful environments. I found that both heterosis and transgression increased as a function of parental divergence, confirming predictions of quantitative genetics theory. Some hybrids were even able to survive in arsenic concentrations lethal for both parents.

Anthropogenic climate change drives up rates of hybridisation between natural populations, yet the potential benefits and risks of hybridisation for the long-term conservation of populations are often unknown. In Chapter IV, I compared the survivability of hybrid populations to their parents under deteriorating environmental conditions. I found that hybrids avoided extinction for a significantly longer time than their parents, at all levels of parental divergence. The more divergent the parents the more similar were the responses of replicate crosses, likely due to the erosion of standing genetic variation in the parental populations.

In summary, my thesis provides a better understanding of the impact of different sources of genetic diversity in determining a population’s capacity to adapt to environmental change.

Aneuploidy is the loss or gain of chromosomes within a genome. It is often detrimental and has been associated with cell death and genetic disorders. However, aneuploidy can also be beneficial and provide a quick solution through changes in gene dosage when cells face environmental stress. Here, we review the prevalence of aneuploidy in Saccharomyces, Candida, and Cryptococcus yeasts (and their hybrid offspring) and analyse associations with chromosome size and specific stressors. We discuss how aneuploidy, a segregation error, may in fact provide a natural route for the diversification of microbes and enable important evolutionary innovations given the right ecological circumstances, such as the colonisation of new environments or the transition from commensal to pathogenic lifestyle. We also draw attention to a largely unstudied cross link between hybridisation and aneuploidy. Hybrid meiosis, involving two divergent genomes, can lead to drastically increased rates of aneuploidy in the offspring due to antirecombination and chromosomal missegregation. Because hybridisation and aneuploidy have both been shown to increase with environmental stress, we believe it important and timely to start exploring the evolutionary significance of their co-occurrence.