This project aims to determine the genetic basis of evolutionary change among mammalian metaorganisms. Through the use of highly sophisticated and unique genetic resources in both the house mouse subspecies complex and humans, we identified highly interesting candidate host loci and microbial taxa that may be involved in adaptation by one or both partners. Common aspects that emerged from both model systems are host genes involved in circadian rhythms and bacterial taxa belonging to Bacteroides.
In the second funding period we will conduct a thorough functional characterization of the most influential candidate host genes and bacterial taxa. This includes the pinpointing of causative mutations, the use of knockout mouse models and the characterization of bacterial strain-level variation. Further, we will improve upon 16S rRNA gene-based mapping by extending mapping efforts to the level of functional elements of the gut microbiome, using shotgun metagenomic sequencing. Importantly, the shotgun metagenomic data will also enable us to extend mapping to non-bacterial elements of the gut microbiome, including novel archaeal taxa in mice.
The A2 project is comprised of a unique combination of evolutionary microbiome research, microbiology and state of the art genetic mapping analysis. The latter is made possible by one-of-a-kind mouse genetic resources and being lead participants in international consortia. Accordingly, our project is the first to clearly identify genetic variation in circadian processes as an aspect of ongoing evolutionary dynamics in mammalian metaorganisms, which will be explored in detail in this funding period.
The overall goal of our project is to identify and characterize the genetic basis of evolutionary change between mammalian metaorganisms. Using the house mouse species complex (A2.1, PI Baines) and Hominidae systems (A2.2, PI Franke), we hypothesize that mammals share themes and mechanisms of host-microbe interaction.
Accordingly, the main joint aims of the first funding period were to (i) identify host genomic regions influencing microbial traits by employing genetic mapping approaches, (ii) perform a fine-scale characterization of candidate bacterial taxa at the genomic level, (iii) identify signatures of coadaptation via population genetic and comparative genomic analyses. This work yielded many interesting results, which importantly include overlap in host genes and bacterial taxa between the two model systems.