A01: Do the shape and size of quasispecies reflect the host range of viruses?
Projects of the CRC 1768
A01: Do the shape and size of quasispecies reflect the host range of viruses?
Viruses exist as dynamic populations of closely related viral genomes arising from mutations, known as quasispecies. We hypothesise that viruses use their quasispecies to expand their evolutionary potential, making them critical for adaptation to new hosts and for resistance to host defences or immunity. Yet, the evolutionary trajectories of viruses cannot be fully understood without considering their ecological context. Host range and environmental conditions act as powerful filters and drivers of viral diversification, raising fundamental research questions at the interface of viral ecology and evolution: How do host interactions and environmental factors shape the emergence, stability, and adaptability of viral quasispecies? If the genetic diversity of the quasispecies reflects the evolutionary potential and ecological interactions of the virus, by which molecular mechanisms do viruses exploit their quasispecies for host range evolution? To address these fundamental questions at the core of our project, we will develop and apply a novel suite of computational tools based on Sequence Variation Graphs (SVGs). SVGs are increasingly utilised for population structure analysis in higher organisms, but their application in virology is limited due to the high mutation rates and genomic diversity of viruses. Nevertheless, they offer potential for analysing data from both genomic and metagenomic samples. In work package WP 1, we will build a quasispecies Sequence Variation Graph (qs-SVG) toolkit that can store sequencing data of viral populations, and we will use and further improve the tool in the remaining work packages. Once the tool is built, we will first apply it to an ideal case where abundant data is available, i.e., SARS-CoV-2 and influenza viruses before, taking on a more challenging case, i.e., bacteriophages found in environmental metagenomes.
The central hypothesis of our project is that viruses use their quasispecies for host range evolution, with specific hypotheses including: (1) Viral quasispecies are shaped by host- and virus-specific factors, and by environmental context; (2) Quasispecies are shaped by targeted mutations, specifically of host interaction genes, leading to host switching.
By combining these two study systems in our project, we will be able to test different functionalities of the qs-SVG toolkit and develop an optimal bioinformatic solution. In WP 2, we will exploit new and existing data on the quasispecies of human viruses and bacteriophages with broad and narrow host ranges, to test the specific hypothesis that viruses with a broad host range also have a large quasispecies. In WP 3, we will investigate under what conditions viruses evolve their quasispecies. We will examine the relationship between quasispecies, host diversity, and the environment, using both in vitro data from isolates, and in situ data by screening metagenomic data sets derived from environmental samples. Finally, in WP 4 we will focus on the underlying mutational mechanisms. How does quasispecies sequence variation arise? Can viruses exploit mutation to expand their host range, and what molecular mechanisms enable this?
The qs-SVG toolkit will provide immediate access to mutations and genetic functions, enabling us to explore the association of these features with variable sites. We will also chart the distribution of the mutational mechanisms across ecosystems and host types (G3). Thus, our new tool suite will facilitate describing, quantifying, and understanding emerging viruses (G1) and offer new perspectives for studying their evolution (G2) in the context of host range.
Project Overview
Based on our preliminary results, viral quasispecies may be accessed by exploiting raw sequencing data, whether from isolates or from enriched complex samples, but existing read-mapping approaches cannot reveal all relevant mutations, as explained above. Thus, we need new analysis tools that are capable of tracking different types of mutations that occur in naturally evolving viral populations. We will develop a bioinformatic tool suite based on SVGs to quantify the mutations in an evolving viral population, extract the trajectories of sequence features (e.g. specific alleles) across datasets (time series), and statistically assess their association with metadata, such as host-range measurements. Furthermore, we will use existing and newly generated data to investigate the ecological imprint on quasispecies, including whether the mutational profile can predict the host range of viruses in eukaryotic and microbial systems. By combining host range profiling, in situ virus-host mapping, and evolutionary co-culture experiments, we aim to uncover how viral microdiversity enables host switching and ecological flexibility. We will test our hypothesis that large quasispecies provide a mutational reservoir that increases potential host range – especially in complex environments like soil – while small quasispecies reflect a narrower host range in stable, low-diversity systems such as groundwater. Finally, we will investigate to what extent these patterns are virus- and host-specific, and associated with mutations that affect specific functional categories of genes. This work bridges viral population genetics with ecological theory to better understand the evolutionary dynamics of virus–host interactions.
- Tool to be developed: A software suite, the quasispecies Sequence Variation Graph (qs-SVG) toolkit, to capture quantify, and investigate viral quasispecies. The qs-SVG toolkit will store diverse sequencing data from viral populations based on complete genomes and unassembled sequencing data, facilitate access to mutations, mutational mechanisms, functional annotations in viral genome sequences, and allow their quantification.
Hypothesis enabled by the proposed tool: The following central and specific hypotheses guide this project.
- Viral quasispecies are shaped by virus- and host-specific factors, and by environmental context
- Host factors: New or suboptimal hosts, recent host switches, diverse hosts, or hosts with a wide array of defence strategies will cause viruses to expand their quasispecies.
- Virus factors: Viruses with rapid genome evolution have large quasispecies, including those encoding diversity-generating elements such as error-prone polymerases or reverse transcriptase-mediated targeted editing, or temperate bacteriophages with high recombination rates.
- Environment: Viruses have large quasispecies in complex environments, e.g., in soil, where the potential for encountering different host cells is high, compared to more homogeneous systems such as groundwater, where hosts are genotypically and phenotypically similar.
- Quasispecies can reveal novel information about viral functions and phenotypes.
- Quasispecies are shaped by targeted evolvability mechanisms such as diversity-generating elements. These molecular mechanisms may be revealed by analysing mutational patterns and may be biotechnologically or clinically relevant.
- Mutations differentially affect specific functional categories of genes, such as receptor-binding proteins and anti-defense genes. Charting quasispecies mutations will thus reveal critical new information about genes involved in host interaction, contributing new insights into tropism and zoonosis.
- Viruses exploit their quasispecies to adapt to different hosts. Viruses with large quasispecies have a broader host range and/or more readily switch to a new host than viruses with small quasispecies.
Overarching CRC goals: Our project develops and applies a quasispecies Sequence Variation Graph (qs-SVG) toolkit to capture, annotate, and quantify intra-population viral diversity from long/short-read and metagenomic data, enabling rapid characterization of emerging viruses and their mutational mechanisms (G1). By deploying qs-SVG across human viruses and environmental phages, the project dissects how ecological context and host diversity shape quasispecies structure, deriving generalisable rules and experimentally testable trajectories of host-range evolution (G2, G3).
Work Packages (WP):
- WP 1: Development of a tool to formally quantify quasispecies (Dutilh)
- WP 2: Measuring the effect of quasispecies on host range and other phenotypic characters (Dutilh/Küsel)
- WP 3: Measuring quasispecies in natural ecosystems and targeted microcosm incubations (Küsel/Dutilh)
- WP 4: Ecological imprint of evolvability mechanisms and implications for classification (Dutilh/Küsel)
Team Members
2025
Ultrafast and accurate sequence alignment and clustering of viral genomes. Journal Article
In: Nat Methods, vol. 22, iss. 6, pp. 1191–1194, 2025, ISSN: 1548-7105.
Hidden viral players: Diversity and ecological roles of viruses in groundwater microbiomes Journal Article
In: 2025.
2024
Graphite: Painting genomes using a colored de Bruijn graph Journal Article
In: NAR Genom Bioinform, vol. 6, no. 4, 2024, ISSN: 2631-9268.
Genome streamlining in Parcubacteria transitioning from soil to groundwater Journal Article
In: Environ Microbiome, vol. 19, no. 1, 2024, ISSN: 2524-6372.
2023
A social niche breadth score reveals niche range strategies of generalists and specialists Journal Article
In: Nat Ecol Evol, vol. 7, no. 5, pp. 768–781, 2023.
2022
Carbon fixation rates in groundwater similar to those in oligotrophic marine systems Journal Article
In: Nat Geosci, vol. 15, no. 7, pp. 561–567, 2022, ISSN: 1752-0908.
High viral abundance and low diversity are associated with increased CRISPR-Cas prevalence across microbial ecosystems Journal Article
In: Curr Biol, vol. 32, iss. 1, pp. 220–227.e5, 2022.
2019
Marine DNA viral macro- and microdiversity from pole to pole Journal Article
In: Cell, vol. 177, iss. 5, no. 5, pp. 1109–1123.e14, 2019, ISSN: 0092-8674.
Molecular and evolutionary determinants of bacteriophage host range Journal Article
In: Trends Microbiol, vol. 27, iss. 1, pp. 51–63, 2019.
2018
Growth promotion and inhibition induced by interactions of groundwater bacteria. Journal Article
In: FEMS Microbiol Ecol, vol. 94, iss. 11, 2018, ISSN: 1574-6941.