Leveraging a phased pangenome for haplotype design of hybrid potato

The tetraploid genome and clonal propagation of the cultivated potato (Solanum tuberosum L.)^1,2 dictate a slow, non-accumulative breeding mode of the most important tuber crop. Transitioning potato breeding to a seed-propagated hybrid system based on diploid inbred lines has the potential to greatly accelerate its improvement³. Crucially, the development of inbred lines is impeded by manifold deleterious variants; explaining their nature and finding ways to eliminate them is the current focus of hybrid potato research^4-10. However, most published diploid potato genomes are unphased, concealing crucial information on haplotype diversity and heterozygosity^11-13. Here we develop a phased potato pangenome graph of 60 haplotypes from cultivated diploids and the ancestral wild species, and find evidence for the prevalence of transposable elements in generating structural variants. Compared with the linear reference, the graph pangenome represents a broader diversity (3,076 Mb versus 742 Mb). Notably, we observe enhanced heterozygosity in cultivated diploids compared with wild ones (14.0% versus 9.5%), indicating extensive hybridization during potato domestication. Using conservative criteria, we identify 19,625 putatively deleterious structural variants (dSVs) and reveal a biased accumulation of deleterious single nucleotide polymorphisms (dSNPs) around dSVs in coupling phase. Based on the graph pangenome, we computationally design ideal potato haplotypes with minimal dSNPs and dSVs. These advances provide critical insights into the genomic basis of clonal propagation and will guide breeders to develop a suite of promising inbred lines.