# Genome-wide evolutionary selection pressures acting on Pseudomonas aeruginosa residing in different environments

## TL;DR

This study compares evolutionary selection pressures in Pseudomonas aeruginosa from cystic fibrosis patients and environmental sources, revealing distinct patterns in gene conservation and function.

## Contribution

The study identifies niche-specific selection pressures and links gene loss in psl biosynthesis to mucA mutations in CF isolates.

## Key findings

- Most ORFs showed strong negative selection, but 373 ORFs displayed non-negative selection.
- CF isolates showed differential selection in 206 ORFs, with metabolic branchpoint enzymes enriched.
- Gene loss in psl correlates with mucA mutations, suggesting compensatory alginate production.

## Abstract

Pseudomonas aeruginosa is an opportunistic pathogen, commonly associated with the airways of people with cystic fibrosis (CF) and in the wider environment too. In this work, we interrogate the International Pseudomonas Consortium Database (IPCD) to ask the question of whether CF-associated isolates display different patterns of evolutionary selection compared with environmental isolates. We do this by analysing dN/dS for each open reading frame (ORF) in the CF-associated and environmental IPCD isolates. Most ORFs displayed a pronounced signature of negative selection (i.e. the ORFs were strongly conserved). However, 373 ORFs displayed non-negative selection, and of these, 206 manifested differential signatures of selection in the CF-derived and environmental isolates. Functional analysis of the ORFs under selection pressure in the CF airways revealed a statistically significant enrichment of enzymes catalysing reactions at metabolic branchpoints. More fine-grained analyses revealed niche-specific selection pressures in individual domains and protein surfaces. Finally, we show that gene loss in the psl biosynthetic gene cluster correlates with the presence of loss-of-function mutations in the mucoidy regulator, mucA. We speculate that elevated alginate production due to these mucA mutations compensates for the loss of Psl production in these isolates.

Graphical Abstract