Functional bottlenecks can emerge from non-epistatic underlying traits

Area of Science:

• Evolutionary biology
• Biophysics
• Computational biology

Background:

• Protein fitness landscapes often display epistasis, where mutation effects are context-dependent, increasing complexity and leading to multiple fitness peaks.
• Global epistasis models fitness as a non-linear function of an additive trait, contrasting with more complex network epistasis involving residue interactions.

Purpose of the Study:

• To introduce and analyze a stylized model of global epistasis with an additive underlying trait.
• To investigate the conditions under which functional bottlenecks emerge in protein fitness landscapes.

Main Methods:

• Analysis of a stylized model of global epistasis.
• Mathematical modeling of protein sequence space and fitness landscapes.

Main Results:

• Functional bottlenecks arise with high probability in the calibrated global epistasis model.
• A balanced ratio of neutral and non-neutral mutations is crucial for the formation of functional bottlenecks.

Conclusions:

• Global epistasis, under specific conditions, can generate the complex topologies of functional bottlenecks observed in protein evolution.
• The balance between neutral and non-neutral mutations is a key factor in shaping protein fitness landscapes and enabling evolutionary pathways.