Projects

 

Can phylogeny predict ally-to-pathogen transitions?

In a recent collaboration with Tal Dagan and Devani Picazo from the Christian Albrechts University in Kiel, we have been working on disambiguating the language of horizontal- and vertical transmission of microbiomes. We found that environmentally inherited microbes — usually assumed to be a mode of horizontal transmission — can yield evolutionary dynamics more akin to vertical transmission, especially when migration is rare.

This preliminary study gives two key insights:

  1. Environmental transmission should not always be conflated with horizontal transmission. What matters is how frequently microbes get exposed to new hosts, reducing the covariance of microbe- and host fitness.

  2. Conditions that promote the evolution of virulent microbiomes (low covariance of fitness) have distinct phylogenies, with very distinct branch lengths (see poster attached to the right-hand side)

Could the phylogenies from real-world microbes be used as early indicators of disease outbreaks?

This poster, presented at a workshop on Evolutionary Transistions in Individuality (2023), indicates that conditions that promote virulence in microbiomes leave very distinct signatures on microbial phylogenies

 
 

Microbial ecology and evolution:
a multi-level approach

Ever since I first learned about the astonishing diversity of microbial communities, I have been unable to stop thinking about these mind-boggling systems. Although our grasp on microbial communities is still lacking, they are an indispensable element of life on Earth. Microbial communities are responsible for completing nutrient cycles in terrestrial, and aquatic ecosystems, and moreover, form intricate symbiotic relationships with larger organisms such as plants and animals. Furthermore, microbial community function has more direct implications for human well-being in terms of the production of antibiotics, gut and skin health, and its relationship to the human immune system.

While it is certainly useful to study complex communities by reducing them to fewer players — e.g. by cultivating small communities in the lab or by using simple mathematical models — such simplification may reduce our ability to understand the processes that are inherent to the complexity itself. In addition to simplification, I argue that embracing the astonishing complexity of microbial communities in our models is a surprisingly productive starting point. This entails implementing models of microbial ecology and evolution with multiple levels of organisation, multiple (potentially conflicting) selection pressures, non-trivial genotype-to-phenotype mapping, and sufficient potential to form complex interactions. Although investigating these models is a major challenge, I believe that these systems are essential to cross-pollinate with experimentalists and bioinformaticians, allowing us to truly get a handle on the unfathomable complexity of microbial communities.

To see a video of what such a multi-level system of ecology and evolution may look like, see the video below:

 
 

Modelling horizontal gene transfer

Horizontal gene transfer (HGT) is the exchange of genes between two organisms without the necessity of a parent-offspring relationship. While virtually non-existent in complex organisms such as ourselves, HGT is very common for bacteria and other microorganisms. By picking up genes via HGT, bacteria can rapidly adapt to new ecological opportunities. However, HGT also risky. For example, by taking up genes from the environment, organisms expose themselves to genetic parasites called selfish genetic elements (SGEs), which simply try to replicate for their own gain.

Through in silico modelling (i.e. computer simulations of biological systems), I study how HGT affects the spread and maintenance of genes, and how this depends on the fitness effects or functions of these genes. With help of these models, I try to investigate when horizontal gene transfer can come to the rescue of a bacterial population, and when it is nothing less than a catastrophe.

Published insights from in silico modelling:

Open questions:

  • When do transposable elements become linked to genes with certain ecological functions, such as antimicrobial resistance?

  • Can transposable elements persist by relying on host-encoded enzymes in order to jump? (e.g. as appears to be the case for RAYT/REPIN transposases)

  • What are the long-term consequences of evolving through HGT (like prokaryotes) and evolving through gene duplications (like eukaryotes)?

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A subpopulation of simulated competent bacteria (yellow/green) overgrowing non-competent bacteria (blue/purple) by being better at retaining slightly beneficial genes.

 
 

Co-evolution of mobile genetic elements, their hosts, and their host’s hosts.

Microbial evolution is driven by rapid changes in gene content mediated by horizontal gene transfer (HGT). These rapid changes are promoted by mobile genetic elements (MGEs), entities that evolved to persist and replicate by moving DNA within and between microbial cells. MGEs are often considered to be on a continuum between parasitism and mutualism, sometimes benefitting their host, and sometimes merely replicating for their own gain. The precise relationships between MGEs and their hosts are complex, ever-changing, and highly dependent upon ecological context. In our team, we build multi-level models of microbial evolution, for example, to understand how MGEs co-evolve with microbial populations and how these interactions affect the health of plants, animals, and ecosystems.

The goal of this project is to understand which types of MGEs are linked to the emergence of plant or animal pathogens, for example by carrying virulence factors as cargo, or by silencing genes that are recognized by the immune system. Vice versa, it will also be interesting to understand why other host-beneficial traits (such as antimicrobial resistance) are less often associated with those same mobile elements, which we suspect has to do with their lifestyle (parasitic vs. mutualistic).

 
 

Open vs. closed ecosystems

As a theoretician, I often study microbial ecosystems by explicitly assuming that “nothing else interferes”. Similarly, experimentalists may try to capture complexity in a bottle by growing communities in the lab. Although this approach allows us to isolate important mechanisms that may shape microbial evolution, natural populations are never that closed. Instead, new biological entities (bacteria, phages, eDNA) may be introduced by processes like migration or diffusion. In one of my old papers, I’ve shown that simulating such an “open ecosystem” results in very different results when compared with a “closed ecosystem”.

Recently, Quistad et al. (2020) have also investigated this distinction between closed and open ecosystems. They periodically collected DNA and SGEs from evolving compost communities and redistributed this cocktail across communities. They show that this has an impact on the community function by enabling the movement of ecologically relevant genes such as cellulose degradation and nitrate reduction. Many questions however remain:

  1. Only a small fraction of the inferred HGT-events was linked to a particular function (a phage or ecologically relevant trait). What entails the other HGT-events?

  2. Are there any consistently moving DNA sequences that appear to not be related to known mobile genetic elements?

  3. Are the “leaky” ecosystems more robust to perturbations like dilution, ph changes, or changes in temperature?

A cartoon of “open”, “closed”, and “leaky” ecosystems.

A cartoon of “open”, “closed”, and “leaky” ecosystems.