EARLYBRID · Investigating the genome and transcriptome dynamics of early interspecific hybridization

Hybridization has shaped the evolution of every kingdom of life. By combining highly diverged genomes, hybridization can drive genetic exchange across lineages. Hybrid genomes often present hallmarks of genome instability, but direct proof of higher rates of mutational events are lacking. What triggers genome instability in hybrids and when it arises remains a mystery. To address this question, I propose to investigate early hybrid history. I seek to conduct a comprehensive characterization of hybrid lethality, genome stability, and gene expression, employing Saccharomyces yeast as a model, due to their tractability and ability to form hybrids despite extreme sequence divergence between parental founders. These studies will focus on the early phases of interspecies hybrid clonal expansion that immediately follow zygote formation. I will first quantify how parental divergence in conjunction with environment influence the genome stability and viability of asexually expanding hybrids. Next, I will combine ultra-long read DNA-sequencing with single-cell RNA-sequencing, to assess the structure and complexity of hybrid genomes, how they evolve over time, and the genomic heterogeneity of hybrid cell populations with single-cell resolution. Finally, by conducting transcriptomic analysis of clonally expanding hybrids, I will determine gene expression dynamics at the onset of hybridization and whether the parental subgenomes converge toward similar gene expression signatures to enter the aforementioned stabilization phase. Mechanistic characterization of the interaction between hybrid viability, genome instability and gene expression phenotypes will provide an unprecedented view of how early hybrid genomes arise, are maintained and evolve.