Saturday, February 22, 2025

Bacteria evolving the ability to evolve with a hypermutable locus

Amazing stuff!

This research was first published in August of 2024 as an bioRxv preprint.

"... To find out, researchers grew Pseudomonas fluorescens bacteria under two sets of conditions: one that favored mat-making, cellulose-producing bacteria, and one that favored ‘cheating’ mat-colonizing, non-cellulose-producing bacteria. The cultures were then swapped, and any bacteria that failed to evolve the other phenotype within 6 days were tossed. While most lineages died out eventually, some evolved the ability to switch between the two forms with ease—thanks in part to mutation rates in a certain part of the genome that were up to 350 times higher than seen in the original bacteria , they report in this week’s issue of Science.

The findings run counter to the idea that evolution is random, the team explains. ..."

From the editor's summary and abstract:
"Editor’s summary
Can the capacity to evolve be selected by natural selection for greater ability to evolve? ... designed experiments in which lineages of bacteria cycled between two selective environments ... In response to changing conditions, a multistep evolutionary dynamic emerged in which selection first acts to elevate transcription rates at a single regulatory gene. An increase in frameshift mutations occurs at the same locus that also allows hitchhiking of secondary, possibly adaptive mutations. This phenomenon provides an evolutionary mechanism for increasing the capacity for evolvability toward specific adaptive outcomes. ...
Structured Abstract
INTRODUCTION
The capacity to generate adaptive variation is critical for long-term evolutionary success. However, the extent to which natural selection directly favors enhanced evolvability remains debated. Although studies with microbes show that mutants with elevated genome-wide mutation rates can be selected, a deeper question persists: Can natural selection structure genetic and developmental systems to bias mutations toward adaptive outcomes? This hypothesis challenges the traditional view of evolution as a “blind” process fueled by random variation, which amplifies traits beneficial in the present without regard for future contingencies.
RATIONALE
Mutation being biased toward adaptive outcomes challenges conventional perspectives but aligns with the logic of natural selection acting on lineages. Across changing environments, lineages capable of rapid adaptation are more likely to survive and replace those less able. If competing lineages, because of their varying genetic architecture, tend to generate phenotypic variation in different ways, then those with tendencies that are more conducive to an adaptive response in a given environment will be favored. Provided the same environmental challenges recur over time, an iterative process of selection can take place, potentially refining the capacity to adapt.
To test this idea, we designed an experiment where lineages of bacteria competed to repeatedly achieve, through mutation, phenotypes optimal for growth under two alternating conditions. Lineages that failed to evolve the target phenotype within a set time went extinct and were replaced by successful lineages. This birth-death dynamic created conditions for selection to refine the ability of lineages to evolve between phenotypic states.
RESULTS
During the course of a 3-year selection experiment, involving identification and ordering of more than 500 mutations, a lineage emerged that was capable of rapid mutational transitions between alternate phenotypic states through localized hypermutation.
The mutable locus arose through a multistep evolutionary process: Initial mutations targeted a wide range of genes but eventually focused on a single regulator. A series of mutations that alternately activated and inactivated function of the regulatory gene then followed. A subset of these inactivating mutations were compensated for by mutations that increased transcription and, concomitantly, frameshift mutation rate. The overall effect was to promote, through slipped-strand mispairing, the duplication, and then further amplification, of a heptanucleotide sequence. This process led the locus-specific mutation rate to increase ~10,000-fold. In turn, the resulting frameshift mutations enabled reversible phenotypic changes through expansion and contraction of the heptanucleotide sequence, mirroring the contingency loci of pathogenic bacteria. Lineages with the hypermutable locus exhibited enhanced evolvability to altered rates of environmental change and were more likely to acquire additional adaptive mutations, highlighting an unanticipated evolutionary advantage of localized hypermutability.
CONCLUSION
Our study demonstrates how selection can incorporate evolutionary history into the genetic architecture of a single cell, giving rise to a hypermutable locus that appears to anticipate environmental change, thereby accelerating adaptive evolution. This was possible only as an outcome of selection working at two levels. Whereas individual-level selection repeatedly drove cell populations between the same two phenotypic states, the genetic underpinnings of these phenotypes were free to diverge, fueling an exploration of evolutionary potential, the consequences of which only emerged on the timescale of lineages. Ultimately, this exploration generated the variation necessary for construction and cumulative refinement of a lineage-level adaptive trait. More generally, our experiment clarifies the conditions by which evolvability can itself evolve adaptively and highlights the importance of this process for microbial pathogens."

ScienceAdviser

Bacteria evolve to get better at evolving in lab experiment "When bacteria were put in alternating environments, some became better at evolving to cope with the changes – evidence that “evolvability” can be gained through natural selection"



Experimental evolution of evolvability through lineage selection.


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