Sorghum and maize share a close evolutionary history that can be explored through comparative genomics. To perform a large-scale comparison of the genomic variation between these two species, we analyzed 13 million variants identified from whole genome resequencing of 468 sorghum lines together with 25 million variants previously identified in 1,218 maize lines.Deleterious mutations in both species were prevalent in pericentromeric regions, enriched in non-syntenic genes, and present at low allele frequencies. A comparison of deleterious burden between sorghum and maize revealed that sorghum, in contrast to maize, departed from the "domestication cost" hypothesis that predicts a higher deleterious burden among domesticates compared to wild lines. Additionally, sorghum and maize population genetic summary statistics were used to predict a gene deleterious index with an accuracy higher than 0.5. This research represents a key step towards understanding the evolutionary dynamics of deleterious variants in sorghum and provides a comparative genomics framework to start prioritizing them for removal through genome editing and breeding. 2 Main text: Sorghum ( Sorghum bicolor L. Moench) and maize ( Zea mays L.) are both members of the Poaceae family and often serve as a model system for comparative plant genomics. Their common Poaceae ancestor underwent a whole-genome duplication (WGD) event ~96 million years ago 1 , and a second WGD in maize corresponds closely with its divergence 12 million years ago from sorghum 2 . The role of polyploidization in maize diversification 1 makes the sorghum-maize system particularly powerful for comparative studies.A rchaeobotanical studies support a single sorghum domestication event around 3000 BC in Eastern Sudan 3 , with genetic studies supporting a potential second independent domestication center in west Africa 4,5 . Maize, in contrast, was domesticated once from teosinte in the Balsas river valley in central Mexico around 9000 years ago 6,7 . While some orthologs between these two species experienced parallel selection during domestication 8 , most domestication related genes appear to be drawn from a non-overlapping set 9 . It is well established that maize experienced a decline in effective population size due to a domestication bottleneck 10,11 that increased the burden of deleterious alleles in the domesticate compared to teosinte 12,13 .Evidence for reduced nucleotide diversity in landraces from a genetic bottleneck 5 or population size decline 14 has also been reported for sorghum.Sorghum has a hermaphroditic inflorescence, contributing to its predominantly self-pollinating nature. Domesticated sorghum has an estimated outcrossing rate of only 7 to 20% 9,15 , while the outcrossing rate tends to be higher (up to 70% 16 ) for weedy and wild sorghum. In contrast, maize and its wild progenitor teosinte are monoecious and generally outcrossing at a rate of over 90% 17 . In this study, we performed a joint analysis of functional variation in sorghum and 3 maize lines that span th...