Eukaryotic genomes contain thousands of genes organized into complex and interconnected genetic interaction networks. Identifying genetic interactions that arise during experimental evolution is important because (i) a global understanding of genetic interaction networks, and how network perturbations affect cellular function, is crucial to preventing and treating human disease, and (ii) genetic interactions impose constraints on evolution by permitting (or prohibiting) subsequent evolutionary change. We are developing high-throughput methods to quantify the fitness effects of hundreds of mutations from our laboratory-evolved populations, both individually and in combination with each other. We have demonstrated that both genetic hitchhiking (luck) and genetic interactions play a significant role in determining which mutations ultimately succeed and fail. By studying evolution in hundreds of replicate populations, we hope to learn how initial steps along an evolutionary path constrain future evolution.
Ploidy varies considerably in the natural world from bacteria that are mostly haploid to some plants that can exist as decaploid. Furthermore, all sexual organisms alternate between ploidy states through gamete fusion and meiosis. The budding yeast, Saccharomyces cerevisiae, can be stably propagated asexually in both haploid and diploid states, providing an ideal system for studying the effect of ploidy on adaptation. In principle, how ploidy impacts adaptation depends largely on assumptions regarding the dominance of new beneficial mutations. Both theory and experimental work support the notion that haploids adapt faster than diploids, presumably due to access to recessive beneficial mutations. Curiously, however, many laboratory-evolving haploid populations undergo whole-genome duplication events yielding populations of diploid yeast. We are using experimental evolution to study the causes and consequences of ploidy changes during evolution. One immediate effect is that diploids accumulate recessive deleterious mutations which can be revealed by traditional tetrad dissections.
Nearly all genomes contain genetic parasites that replicate selfishly, often at a cost to the host genome. Evolutionary arms races between selfish genetic elements and their hosts drive speciation events and have contributed to the origin of sex and the evolution of sex chromosomes. All genomes, including the human genome, exhibit clear signatures of past intragenomic conflicts. Yet our understanding of intragenomic conflict is limited in that few systems exist to study the mechanisms by which evolution resolves these conflicts. We are leveraging experimental evolution to study various types of genetic conflict in yeast, including sexual conflict, gene drive, and the selfish intracellular "Killer" virus. The yeast Killer virus is an encapsulated double-stranded RNA virus that encodes both a Killer toxin and its corresponding immunity component. An infected host secretes the toxin, which kills non-Killer-containing cells. A Killer+ strain produces a zone of inhibition by impeding the growth of a sensitive lawn (left). An evolved strain that has lost the Killer virus no longer produces the zone of inhibition (right).