Analysis of progenitor genomes offers insights to reduce deleterious burden in hybrid potato breeding

Hybrid potato breeding aims to transition potato from clonal tetraploid to seed-propagated diploid. However, this process is hindered by historically accumulated deleterious variants, resulting in weak field performance of existing homozygous inbreds and compromised heterosis in hybrids. To accelerate genome design for hybrid potato breeding, it is essential to understand how deleterious variation was reshaped during domestication and whether this knowledge can guide purging of deleterious variants. To address this, we constructed a genome-wide deleterious variant map spanning 502 accessions, including both progenitor and landrace materials. Compared to landrace panel, the progenitor panel displayed a higher genetic diversity, longer genetic distance and a lower frequency of deleterious variants, properties expected to enhance heterosis and guide the purging of deleterious variants. Moreover, deleterious variants, including those subject to turnover accumulation and even fixation during domestication, were preferentially enriched in selective sweeps in the landrace panel. All these illustrated a clear "hidden cost" of domestication. Consistent with this, deleterious variants in potato hybrid and their landrace-derived inbred parents increased about twofold in allele frequency during domestication, pointing to the potential of CND accessions as donors for inbreds improvement. We predicted a progenitor-assisted genome with about half the deleterious burden of inbreds by leveraging the deleterious map of the CND progenitor, providing a predictive genomic framework for guiding future purging of deleterious variants during inbred improvement. Our work bridges domestication genomics with genome-design breeding and shifts the use of wild progenitors from single-gene introgression toward genome-wide optimization.