Genetic constraints on adaptive evolution

Evolution has often been shown to be repeatable and even predictable within species. But as species diverge, evolution becomes less predictable due to differences in genetic constraints. These constraints can be altered by mutation rates, pleiotropy or historical contingency, but ultimately they result in adaptation becoming more restricted or even inaccessible is some species relative to others. Whereas much has been learned about the genetic basis of adaptation, comparably little is known about how constraints diverge between species and limit adaptive potential. The goal of our research program is to unravel the ways in which constraints limit adaptation and how these constraints diverge between species. We will build on our work in the Saccharomyces yeast species, where we have characterized constraints on multi-step thermal adaptation and single-step evolution of copper and sulfite resistance. For thermal adaptation we have shown that multiple genes are necessary but not sufficient for high thermotolerance, a hallmark of complex adaptations. We have also shown there is widespread divergence in protein thermal stability and that these stability differences are predictable. Establishment of this groundwork now enables us to identify and evaluate individual adaptive steps, species differences in constraints acting on these steps, and test a model of evolutionary ratcheting, whereby small incremental steps become entrenched during adaptation and necessary for thermotolerance or thermostability. For copper and sulfite resistance we will determine why some but not other species are constrained in their evolution of resistance. Our work thus far supports a model whereby single-step adaptations in extant lineages are dependent on prior changes in constraint that are far more complex and so not easily overcome. Together, our research projects seek to explain how seemingly subtle or obtuse differences between species can become critical components of adaptive traits and form major constraints on an organism’s adaptive potential. Project Number: 1R35GM156247-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Justin Fay | Institution: UNIVERSITY OF ROCHESTER, ROCHESTER, NY | Award Amount: $227,435 | Activity Code: R35 | Study Section: Maximizing Investigators' Research Award - F Study Section[MRAF] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R35GM15624701