# Rapid evolutionary change in trait correlations of single proteins

## TL;DR

This paper shows how traits of proteins can rapidly evolve together due to changes in protein folding, affecting the potential for new adaptive traits.

## Contribution

The study reveals that protein foldability mutations can rapidly alter trait correlations, influencing evolvability.

## Key findings

- Correlations between traits in fluorescent and antibiotic resistance proteins evolve rapidly through mutation and selection.
- Changes in protein foldability drive shifts in trait correlations.
- Mutations affecting foldability may influence complex trait correlations across many proteins.

## Abstract

Many organismal traits are genetically determined and covary in evolving populations. The resulting trait correlations can either help or hinder evolvability – the ability to bring forth new and adaptive phenotypes. The evolution of evolvability requires that trait correlations themselves must be able to evolve, but we know little about this ability. To learn more about it, we here study two evolvable systems, a yellow fluorescent protein and the antibiotic resistance protein VIM-2 metallo beta-lactamase. We consider two traits in the fluorescent protein, namely the ability to emit yellow and green light, and three traits in our enzyme, namely the resistance against ampicillin, cefotaxime, and meropenem. We show that correlations between these traits can evolve rapidly through both mutation and selection on short evolutionary time scales. In addition, we show that these correlations are driven by a protein’s ability to fold, because single mutations that alter foldability can dramatically change trait correlations. Since foldability is important for most proteins and their traits, mutations affecting protein folding may alter trait correlations mediated by many other proteins. Thus, mutations that affect protein foldability may also help shape the correlations of complex traits that are affected by hundreds of proteins.

Trait correlations impact evolvability as selection on one trait can influence others. Here, the authors examine trait correlation in two proteins, a fluorescent protein & an antibiotic resistance enzyme, observing rapid evolution of trait correlations through changes in the biophysical properties of these proteins.