Protein evolution

How Does Biological Organization Influence Molecular Evolution?

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Across diverse biological systems, we investigate how hierarchical organization shapes evolutionary dynamics. At the molecular level, we have shown that protein stability modulates site-specific rate variation (Dasmeh et al., 2013), and that epistasis itself is constrained by folding stability (Dasmeh et al., 2014), such that interactions among mutations are structured by biophysical context (Dasmeh et al., 2017).

 

In microbial systems, we have demonstrated that antibiotic resistance evolves through threshold-like relationships between molecular function and organismal fitness (Erdogan et al., 2024), and that correlated traits can influence the evolutionary trajectories through their interconnected effects. Mutations that affect protein stability further module trait correlations and influence the evolution of novel phenotypes (Dasmeh et al., 2024).

 

At the systems level of complex and polygenic traits, we explore how the architecture of gene regulatory networks and polygenic phenotypes conditions the distribution and effect of genetic variation, just as different amino acid positions evolve at distinct rates due to their structural roles (Giel et al., 2024). This comparative approach leads us to ask whether natural selection not only shapes specific functions, but also preserves organizational properties that facilitate the evolvability of polygenic phenotypes, enabling populations to respond to selection across scales of biological organization.