Using Pool-seq to Search for Genomic Regions Affected by Hybrid Inviability in the copepod T. californicus

The formation of reproductive barriers between allopatric populations involves the accumulation of incompatibilities that lead to intrinsic postzygotic isolation. The evolution of these incompatibilities is usually explained by the Dobzhansky-Muller model, where epistatic interactions that arise within the diverging populations, lead to deleterious interactions when they come together in a hybrid genome. These incompatibilities can lead to hybrid inviability, killing individuals with certain genotypic combinations, and causing the population's allele frequency to deviate from Mendelian expectations. Traditionally, hybrid inviability loci have been detected by genotyping individuals at different loci across the genome. However, this method becomes time consuming and expensive as the number of markers or individuals increases. Here, we test if a Pool-seq method can be used to scan the genome of F2 hybrids to detect genomic regions that are affected by hybrid inviability. We survey the genome of hybrids between 2 populations of the copepod Tigriopus californicus, and show that this method has enough power to detect even small changes in allele frequency caused by hybrid inviability. We show that allele frequency estimates in Pool-seq can be affected by the sampling of alleles from the pool of DNA during the library preparation and sequencing steps and that special considerations must be taken when aligning hybrid reads to a reference when the populations/species are divergent.