Dynamics of deleterious mutation and selection at seven nuclear genes during barley domestication and de-domestication.

Understanding how barley domestication affects deleterious mutations is crucial for breeding and germplasm conservation. This study analyzed seven single-copy nuclear genes (Alcohol dehydrogenase 2 (ADH2), Alcohol dehydrogenase 3 (ADH3), Dehydrin9 (DHN9), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Phosphoenolpyruvate carboxylase (PEPC), Photoperiod response gene (PPD-H1), and Granule-bound starch synthase (WAXY)) in 179 wild, 185 domesticated, and 21 de-domesticated barley accessions. Results showed that wild barley has the highest genetic diversity and the most private haplotypes. Deleterious SNPs were identified, with fewer in domesticated and de-domesticated groups compared to wild. Deleterious mutation load decreased from wild to domesticated barley as nucleotide diversity decreased (R = 0.78; p < 0.05), suggesting that domestication bottlenecks may purge these mutations. In wild barley, Nonsynonymous-to-synonymous substitution rate (dN/dS) ratios were ~ 1 or > 1, indicating neutral or weak positive selection. These findings highlight how domestication shapes deleterious mutation patterns and provide insights for breeding and germplasm management.