Ecological drivers of intragenomic conflict resolution

Lead Research Organisation: University of Manchester
Department Name: School of Biological Sciences


The classical view of evolution is as a process of gradual accumulation of small changes by mutations passed on to descendants. However, genome sequencing has revealed that in bacteria genes are frequently exchanged between cells and species by a process called horizontal gene transfer, allowing evolution to make big, fast jumps. Genes often pass from one bacterial cell to another on circular pieces of DNA called plasmids. However, acquiring a plasmid can be costly to a bacterial cell because plasmids use energy and introduce new genes that disrupt the normal working of the bacterium. In evolutionary theory these costs are called intragenomic conflicts because what is good for the plasmid is bad for the bacterial chromosome, and vice versa. We have recently shown that evolution can resolve these conflicts by a process of 'compensatory evolution', whereby either the bacterial chromosome or the plasmid gains mutations that lessen the cost of carrying the plasmid. By increasing plasmid survival, compensatory evolution is likely to increase the chance of new genes jumping onto plasmids from bacterial chromosomes, allowing these to be shared with other species in the community. In this proposal we will discover how the ecology of microbial communities and the environments they live in shape the processes of compensatory evolution, and whether compensatory evolution itself speeds up the sharing of genes between species.

Planned Impact

Who will benefit from this research and how?

This is basic blue-skies research that will advance fundamental understanding of evolutionary processes and dynamics in bacterial communities. Nevertheless, bacterial evolution has a broad range of important impacts upon society, for example through the effects of rapid evolutionary change on the prognosis of clinical infections, the evolutionary emergence of antibiotic resistance, and evolutionary responses of microbial communities underpinning the functioning of ecosystems to environmental change. Despite the widespread and fundamental impact of rapid microbial evolution in general and horizontal gene transfer (HGT) in particular upon society, these evolutionary processes remain very poorly understood by the general public and policy-makers. The key benefits deriving from this research will therefore be increased knowledge and understanding of bacterial evolution among the following groups:

Secondary school age children: Teaching of evolution in Key Stages 2 and 3 of the National Curriculum is mainly theoretical and lacking in engaging practical classes. We will take experimental evolution into the school classroom allowing pupils to experience evolution in action themselves in real time, generating excitement about microbes and evolution and offering deeper experiential learning.

General public: Bacterial evolution is high on the news agenda due to the crisis in antimicrobial resistance (AMR), however few non-scientists realise that this societal problem is exacerbated by HGT-mediated evolution. Public engagement activities will enhance public understanding of HGT and put this into the context of AMR to show what we can all do to reduce the risks of AMR.

Policy makers in healthcare and agri-food sectors: HGT impacts the evolutionary emergence of AMR in the clinic and the spread of functional traits in soil bacterial communities. Designing policies and interventions that aim to e.g. limit the spread of AMR or conserve the functional diversity of soil bacterial communities, requires sharing knowledge and understanding of the dynamics of HGT and how these are shaped by the ecology of microbial communities and their environments arising from this research with stakeholders and policymakers in these sectors. We will engage with healthcare stakeholders via an established clinical network (PARC; PI Brockhurst is a member) and agri-food stakeholders via the N8 AgriFood Partnership facilitated by the N8 AgriFood Knowledge Exchange Fellows.


10 25 50
Description Bacteria rapidly adapt to new environments increasing their fitness. We show that this process of environmental adaptation is prevented by the presence of other bacterial species in simple communities in soil microcosms. Published in Evolution Letters.
Acquisition of plasmids causes costs for the host cell which can be ameliorated by mutations elsewhere in the genome (compensatory mutations). Using mathematical models we show that plasmid survival is enhanced when these compensatory mutations are encoded on the plasmid itself, rather than on the bacterial chromosome. Published in mSystems. Using RNA sequencing to compare gene expression in bacteria with or without plasmids we show that the costs of plasmid acquisition are caused by genetic conflicts between genes on the chromosome and plasmid, causing deleterious expression of other mobile genetic elements in the bacterial chromosome. These effects are fixed by compensatory mutations, restoring normal gene expression. Published in PLOS Biology. Bacteria can rapidly adapt to the costs of acquiring plasmids by gaining compensatory mutations to overcome intragenomic conflict. Published in Microbiology. Moreover, a single chromosomal compensatory mutation can ameliorate the cost of carrying multiple plasmids in the same cell. Published in mBio.
The dynamics of plasmids in bacterial populations and communities are shaped by spatio-temporal variation selection for the traits carried by plasmids and also by the structure of the microbial community and the abilities of the constituent species to act as hosts for the plasmid(s). Published in Proceedings of the Royal Society B, FEMS Microbiology Ecology, and Microbiology.
We also published a major review on the ecology and evolution of pangenomes focusing on the importance of intragenomic conflicts and horizontal gene transfer. Published in Current Biology.
Exploitation Route These findings advance understanding of how species evolve in complex communities, which is relevant to understanding how species will adapt to anthropogenic environmental change. These findings advance understanding of how plasmids survive and spread in bacterial populations/communities, which is relevant to understanding the spread of antibiotic resistance genes. These findings reveal how bacterial genomes evolve through the horizontal acquisition of new genetic material from other cells and species.
Sectors Environment,Healthcare

Description The findings from this project have been delivered to the public through outreach activities and helped increase understanding of the role for microbes in health (of soils, plants and animals). The findings have fed into a Parliamentary Office of Science and Technology POSTnote. The finding have formed the basis for a public engagement comic book "Luna and Simon: Bizarre Bacteria and Peculiar Plasmids" about plasmids written by Edward Ross for the general public
First Year Of Impact 2019
Sector Agriculture, Food and Drink,Creative Economy,Digital/Communication/Information Technologies (including Software),Environment,Culture, Heritage, Museums and Collections
Impact Types Cultural,Societal,Policy & public services

Title Population dynamics of evolving bacterial populations in liquid media, 2020 
Description This data was collected from co-evolving bacterial populations containing Pseudomonas fluorescens strain SBW25 and a plasmid, pQBR57. The composition of the community was tracked using flow cytometry to distinguish 1) an unlabelled wild type strain 2) a dTomato compensated host (SBW25 KO PFLU4242), and 3) a wild type host bearing a Green fluorescent protein (GFP) labelled compensated plasmid (pQBR57 KO 0059). 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
Title Population dynamics of evolving bacterial populations in soil, 2020 
Description This dataset describes the composition of a co-evolving community (as colony forming units) over a 30-transfer selection experiment in soil microcosms. The community consists of Pseudomonas fluorescens SBW25 + Pseudomonas putida KT2440 + plasmid pQBR57. 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
Description Public engagement comic book 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Comic book "Luna and Simon: Bizarre Bacteria and Peculiar Plasmids" written by Edward Ross based on our research and accompanying website. Printed and online. Production featured workshops for 20 school children. Over 500 printed copies have been distributed and far more downloaded from the website.
Year(s) Of Engagement Activity 2020