Ken Wolfe studies the evolution of eukaryotic genomes and chromosome organisation. He is best known for his discovery that the genome of the yeast Saccharomyces cerevisiae underwent complete duplication about 100 million years ago, an event we now know to be the result of hybridization between two divergent parental species. This finding reshaped our understanding both of yeast biology, and of mechanisms of genome evolution in eukaryotes. His subsequent discoveries of similar ancient genome duplications in the human lineage, and in almost all families of flowering plants, led to the recognition that whole-genome duplication is a widespread evolutionary mechanism. His group also studies the origin and evolution of mating systems in yeasts, and the process of mating-type switching in which one cell type can change into another by moving or replacing a section of chromosome.

Wolfe is an elected Member of the Royal Irish Academy and of the European Molecular Biology Organization, and a former President of the Society for Molecular Biology and Evolution. He is Professor of Genomic Evolution at University College Dublin.