GENETICS | INVESTIGATION Signatures of Dobzhansky-Muller Incompatibilities in the Genomes of Recombinant Inbred Lines

In the construction of Recombinant Inbred Lines (RILs) from two divergent inbred parents certain genotype (or epigenotype) combinations may be functionally “incompatible” when brought together in the genomes of the progeny, thus resulting in sterility or lower fertility. Natural selection against these epistatic combinations during inbreeding can change haplotype frequencies and distort linkage disequilibrium (LD) relations between loci within and across chromosomes. These LD distortions have received increased experimental attention, because they point to genomic regions that may drive Dobzhansky-Muller-type of reproductive isolation and, ultimately, speciation in the wild. Here we study the selection signatures of two-locus epistatic incompatibility models and quantify their impact on the genetic composition of the genomes of 2-way RILs obtained by selfing. We also consider the biases introduced by breeders when trying to counteract the loss of lines by selectively propagating only viable seeds. Building on our theoretical results, we develop model-based maximum likelihood (ML) tests which can be employed in pairwise genome scans for incompatibility loci using multi-locus genotype data. We illustrate this ML approach in the context of two published A.thaliana RIL panels. Our work lays the theoretical foundation for studying more complex systems such as RILs obtained by sibling mating and/or from multi-parental crosses.