Key features of the genetic architecture and evolution of host-microbe interactions revealed by high-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice

Shauni Doms, Hanna Fokt, Malte Christoph Rühlemann, Cecilia J. Chung, Axel Kuenstner, Saleh M. Ibrahim, Andre Franke, Leslie M. Turner, John F. Baines

Research output: Contribution to journalArticlepeer-review

5 Citations (SciVal)

Abstract

Determining the forces that shape diversity in host-associated bacterial communities is critical to understanding the evolution and maintenance of metaorganisms. To gain deeper understanding of the role of host genetics in shaping gut microbial traits, we employed a powerful genetic mapping approach using inbred lines derived from the hybrid zone of two incipient house mouse species. Furthermore, we uniquely performed our analysis on microbial traits measured at the gut mucosal interface, which is in more direct contact with host cells and the immune system. Several mucosa-associated bacterial taxa have high heritability estimates, and interestingly, 16S rRNA transcript-based heritability estimates are positively correlated with cospeciation rate estimates. Genome-wide association mapping identifies 428 loci influencing 120 taxa, with narrow genomic intervals pinpointing promising candidate genes and pathways. Importantly, we identified an enrichment of candidate genes associated with several human diseases, including inflammatory bowel disease, and functional categories including innate immunity and G-protein-coupled receptors. These results highlight key features of the genetic architecture of mammalian host-microbe interactions and how they diverge as new species form.

Original languageEnglish
Article numbere75419
JournaleLife
Volume11
DOIs
Publication statusPublished - 19 Jul 2022

Bibliographical note

Funding Information:
We thank Diethard Tautz for generous support of mouse breeding and Camilo Medina and the MPI-Plön mouse team for performing mouse husbandry, and Katja Cloppenborg-Schmidt and Dr Sven Künzel for their excellent technical assistance. We thank Jason Wolf for constructive feedback on the statistical models and heritability estimation. We thank Mathieu Groussin for assistance with cospeci-ation rate data. Research funding for this project was provided by the Deutsche Forschungsgemein-schaft (DFG, German Research Foundation), Project-ID 261376515 – Collaborative Research Center 1182, ‘Origin and Function of Metaorganisms’, Project A2 (J.F.B. and A.F.), Cluster of Excellence 2167 ‘Precision Medicine in Chronic Inflammation (PMI)’ (grant no. EXC2167 to A.F. and J.F.B.) and TU 500/2–1 to L.M.T, and by the Max Planck Society (to D Tautz).

Data availability
DNA- and RNA-based 16S rRNA gene sequences are available under project accession number
PRJNA759194. Code is available at https://github.com/sdoms/mapping_scripts, (copy archived at
swh:1:rev:d085e7782e9ac85e264fc6b70a5058a53fd7e9fe).

Keywords

  • codiversification
  • cospeciation
  • evolutionary biology
  • genetics
  • genomics
  • GWAS
  • hybridization
  • microbiome
  • mouse
  • phylosymbiosis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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