From pattern to function: eco-evolutionary representations of complex spatial structure for the new era of spatial biology

Through innovations in both imaging techniques and the ability to process these images at scale, high-
resolution imaging is transforming the eld of molecular biology, yet its power has yet to be fully utilized
for asking questions in evolutionary biology. Just as demographic surveys can reveal more or less densely
populated areas where, for example, a contagious disease may spread at di erent rates, these imaging
datasets can help us quantify cellular and molecular patterns of spatial variation and understand how this
variation a ects rates of evolution, by impeding or accelerating the spread of new variants through the
population. My research program, at the interface of computer vision and evolutionary biology, is exploring
how molecular and cellular communities spatially organize, and how the resulting spatial topologies can
be generated, stably maintained and further shape the outcome of the evolutionary process.
What are spatial topologies that act to amplify the selective advantage of new mutations in the pop-
ulation, versus structures that dampen the force of selection and slow down rates of evolution? We build
theoretical evolutionary models that explore how the rate of evolution is shaped by complex spatial struc-
ture and nd the relevant spatial features for evolutionary ampli cation or selective suppression. We link
these theoretical population genetic models to high-resolution imaging datasets and study the resulting
spatial architectures. This allows us to go beyond simply describing patterns of cellular or molecular spatial
variation, and enables exploration of the generative processes, as well as of the evolutionary trajectories of
the system.
Beyond the purely theoretical interest in these questions, understanding the role of spatial structure
in shaping the mode and tempo of evolutionary dynamics is particularly timely because, by using modern
microfuidics and organoid technologies, we can start building population structures that control the topol-
ogy and migration patterns of a molecular or cellular population, amplifying the selective bene t of chosen
mutations, boosting the ability to nd optimized protein complexes for medical or industrial applications,
or as a screening tool for faster replicating pathogenic variants.

Grant Number: 5R35GM147445-04
NIH Institute/Center: NIH
Principal Investigator: Oana Carja