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. • Our study characterized deleterious mutation and selection pressure at seven nuclear genes in domesticated barley and its wild relatives. • The deleterious mutation load declined from wild to domesticated groups, correlating with reduced nucleotide diversity, suggesting that domestication bottlenecks purged deleterious mutations. These genes displayed nearly neutral or weakly positive selection in wild barley. • Our findings have implications for understanding mutational dynamics and for the conservation and utilization of germplasm resources.