Systematic Characterization of Hybrid Incompatibilities between Nematode Species

It has long been noticed that many closely related species are able to mate with each other but their hybrid progeny frequently suffer from early developmental abnormality or sterility, a phenomenon called post-zygotic hybrid incompatibility (PHI). PHI is not only found between different species, but also observed between different populations within the same species. PHI serves as a fundamental biological process behind biodiversity. It is believed that PHI involves abnormal interactions between at least two genes from each parent, but the molecular and cellular mechanisms of PHI remain largely unknown. Mechanistic research of PHI will not only provide insights into how a species maintains its genomic integrity to ensure proper development of tissues and organs, but also will shed light on unexplained miscarriage and sterility in human.

In addition to the classical molecular and genetic methods required for studying a gene with unknown function, isolation and characterization of PHI loci demand unique tools. In particular, it requires a pair of closely related species, called sister species that can mate with each other and produce viable progeny. Thus, if a sister species can be found for a model organism, it is common to take advantage of these species for identification of PHI loci due to availability of abundant molecular and genetic tools. However, C. elegans as a model organism is prevented from such studies due to lack of a sister species. C. briggsae is another nematode species closely related to C. elegans. Its sister species, sp.9 has recently been isolated, opening the door for the isolation and characterization of PHI loci using the species pair.

We have previously developed multiple molecular and genetic tools in C. briggsae. Here, we propose to develop new tools and resources in C. briggsae and use them for systematic characterization of PHI loci between C. briggsae and sp.9. To that end, we will first generate and map a total of approximately 200 stable transgenic C. briggsae strains expressing fluorescent markers. We will then repeatedly introduce the markers into an otherwise sp.9 background to isolate the marker linked C. briggsae genomic fragments that produce developmental defects in sp.9 species. We will characterize the cellular events for a subset of the PHI strains by our automatic lineaging technique. The resulting GFP strains will lay down a long term platform to use nematode species for isolation and characterization of PHI loci.