The genetic basis of phylosymbiosis and microbe-mediated hybrid lethality

• Applicant: Dr. Aram Mikaelyan
• Subject Area: Evolutionary Cell and Developmental Biology (Zoology) ; Immunology ; Microbial Ecology and Applied Microbiology
• Term: from 2017 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 390375589

The intestinal tracts of animals house some of the densest communities of microbial symbionts, and studies over the last decade have elucidated their astounding roles in host biology. In several cases, the fidelity of host-microbiota associations is reflected by host-specific composition of these gut bacterial communities and their metagenomes. Moreover, gut bacterial community relationships can recapitulate the evolutionary relatedness of the host species – a pattern known as “phylosymbiosis”. Notably, disruptions of phylosymbiosis in gut bacterial communities can be linked to severe maladies in hybrid hosts and could be driving host speciation. What are the host genetic factors and mechanisms that regulate phylosymbiosis? How do these genes influence hybrid conditions associated with the gut microbiota? The central hypothesis of this proposal is that phylosymbiosis and microbe-dependent hybrid lethality result from (1) an abnormal migration of gut bacteria into the hemolymph and (2) a misexpression of particular immune genes in hybrids that would otherwise control the resident bacterial population in pure species. The Nasonia wasp model system is ideal to test these hypotheses, because gut microbiota have been observed to contribute to severe larval lethality in interspecific hybrids. Using this model system, I will address the following two aims:I: Track bacterial colonization of the gut and identify the host genes that are hyperexpressed in hybrids in response to gut colonization. Proteus mirabilis is a widespread member of the Nasonia gut microbiota and contributes to hypermelanization and death of gnotobiotic Nasonia hybrids. This aim will use GFP-tagged P. mirabilis to test the hypothesis that, in the pure species, the bacterium exists in the benign, “swimmer” morphotype, but differentiates into the more virulent, “swarmer” morphotype in the hybrid to cause melanization in the hemolymph followed by death. The proliferation rate and sites of P. mirabilis will be studied using fluorescence microscopy. Additionally, RNA-seq analysis and qPCR in germ-free and wasps colonized by microbiota will test the hypothesis that specific candidate immune genes in the hybrid are involved in lethal breakdown in host-microbiota interactions.II: Functionally interrogate candidate genes underlying hybrid lethality and phylosymbiosis. Candidate genes responsible for hybrid lethality and phylosymbiosis will be shortlisted based on expression profiles obtained in Aim 1 from hybrid and non-hybrid larvae. This aim will test the hypothesis that when an important candidate gene for hybrid lethality is repressed by RNAi or CRISPR, hybrid viability will be restored. Moreover, repression of the same genes within species will disrupt a phylosymbiotic community assembly, thus probing the hypothesis that the same genes that influence hybrid lethality also influence phylosymbiosis.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Seth Bordenstein, Ph.D.