I am an evolutionary geneticist who combines experimental and computational methods to study two fundamental topics in evolutionary biology: the evolution of multicellularity and the origins of species.
The Multicellularity Long-Term Evolution Experiment (MuLTEE)
My main research focuses on the Multicellularity Long-Term Evolution Experiment (MuLTEE), inspired by Richard Lenski’s LTEE with bacteria. This experiment examines the transition to multicellularity using ‘snowflake’ yeast, a simple model of nascent multicellularity developed by Will Ratcliff and Mike Travisano.
Generating a long-term evolution experiment to study the evolution of simple multicellularity has been challenging due to a lack of understanding about the constraints on the evolution of significant changes in previously developed models. Since multicellular size is a key trait under selection, most models of multicellularity have been limited in their ability to evolve large multicellular size.
During my postdoctoral research, we overcame this challenge through a crucial discovery: oxygen’s complex role in the evolution of multicellular size. By evolving snowflake yeast across a range of oxygen levels, we revealed a non-linear relationship between oxygen availability and size evolution. Both anaerobic and high-oxygen conditions promoted larger size, while intermediate oxygen levels constrained it. This pattern stems from nearly universal evolutionary and biophysical trade-offs and provides insights into how environmental oxygen availability may have shaped the timing and trajectory of complex life’s evolution on Earth.
This discovery allowed us to lift constraints on multicellular size evolution, leading us to turn the MuLTEE into an open-ended evolution experiment, which I am still leading in the Ratcliff lab. The experiment has already yielded significant results, with snowflake yeast evolving mm-scaled multicellular groups visible to the naked eye. They achieved this by evolving more elongate cells and a novel ‘entangled’ morphology, resulting in groups ~20,000x larger than their ancestor and as strong and tough as wood.
Now in its fifth year and spanning approximately 8,500 generations, the MuLTEE is the only long-term evolution experiment of multicellularity. Our goal is to run this experiment for over 20 years, providing an unparalleled opportunity to study multicellular evolution in real-time. We’re monitoring how macroscopic multicellularity affects the fitness, genome, transcriptome, phenotype, and life cycle of both individual cells and multicellular groups.
The MuLTEE serves as a hypothesis generation machine, allowing us to explore various aspects of this major transition in evolution. It has also led to spin-off projects examining the evolution of genome duplication, reductive evolution of mitochondria to mitochondria-related organelles (aka MROs), and the divergent transcriptomics of yeast into three distinct metabolic conditions (anaerobic, mixotrophic, and aerobic). In just the last three years, this long-term project has generated five research papers, including articles published in Nature, Nature Ecology & Evolution, Nature Communications, and Science Advances. The work has been highlighted in National Geographic and The Atlantic, generated over 10 Ph.D. thesis chapters, and involves 30 scientists from various laboratories across the globe.
See a research highlight about key aspects of this work, written by Or Shalev and collegues: Replaying the Evolution of Multicellularity
Research on the genetics of reproductive isolation and origin of species
Additionally, I am interested in understanding the genetic mechanisms of reproductive isolation and species formation in yeast. In a breakthrough study, we discovered that by repressing just two genes (SGS1 and MSH2) during meiosis, we could dramatically increase hybrid fertility between two diverged yeast species, Saccharomyces cerevisiae and S. paradoxus. This genetic manipulation raised hybrid gamete survival from less than 1% to 32%, comparable to non-hybrid crosses. This finding demonstrates that anti-recombination is the principal cause of hybrid sterility between these species.
By overcoming this barrier, we produced viable, euploid hybrid gametes with recombinant genomes from highly diverged parents. This discovery not only advances our understanding of speciation but also provides a valuable tool for yeast researchers. It enables the creation of hybrid strains with novel properties, facilitates trait mapping across species, and opens new possibilities for both basic research and biotechnology applications.
Please see our review paper on this topic: Evolution and Molecular Bases of Reproductive Isolation
Press coverage about our work
• The Atlantic:
One of evolution’s biggest moments was re-created in a year
• National Geographic:
Evolving globs of yeast may unlock mysteries of multicellular life
• The New York Times:
An experiment repeated 600 times finds hints to evolution’s secrets
• Science Daily:
Did Earth’s early rise in oxygen help multicellular life evolve?
• Quanta Magazine:
Single cells Evolve large multicellular forms in just two years