The life history of recessive deleterious alleles as seen through the eyes of a honey bee (Apis mellifera).

Deleterious mutations arise continually in natural populations, yet their full life histories-from origin to elimination-are rarely observed directly. Our understanding of mutational fate in the wild comes from indirect inference rather than from tracking a single mutation through time and space. Haplodiploid systems provide a rare opportunity to observe negative selection in action: because males are haploid, recessive alleles are immediately exposed to selection rather than masked by heterozygosity. Haplodiploidy has long been hypothesized to accelerate the purging of deleterious variation. Here, we leverage the honey bee as a model system to document the complete trajectory of a spontaneous deleterious mutation, from its origin in a single queen to its extinction. The mutation alters eye pigmentation in haploid males, enabling us to quantify its molecular, physiological, and behavioral consequences through integrated genomic, transcriptomic, proteomic, and metabolomic analyses. By following this mutation across generations, we directly observe how haplodiploidy exposes recessive alleles to immediate purifying selection and how mating structure and colony demography influence their persistence. This study represents one of the few documented cases of a naturally occurring mutation tracked through its full evolutionary course, offering a rare empirical view of how selection operates in real time within a social, haplodiploid genome.