Not just mutations: inbreeding depression persists without genetic variation

Abstract Inbreeding depression (ID)—the reduction in fitness with increasing parental relatedness—is classically attributed to the expression of recessive deleterious mutations in homozygous individuals. Yet, the assumption that ID can only arise from changes in genetic heterozygosity has rarely, if ever, been directly tested. To test this, we produced highly inbred lines (F = 0.99999997) of the freshwater snail Physa acuta and generated offspring that differed in parental relatedness (self-fertilization, sib or cousin matings) while their parents, produced by crossing two inbred lines, all shared an identical genome. Several fitness traits showed significant declines with increasing parental relatedness. These traits included juvenile survival, body size, and self-fertility, and the magnitude of their decline was equivalent to a substantial fraction of the ID observed in natural, genetically polymorphic populations of P. acuta. Individual-based simulations demonstrated that spontaneous mutation rates compatible with natural levels of ID are far too low to account for the magnitude of ID observed here. These findings suggest that non-genetic mechanisms, most plausibly involving heritable epigenetic changes, can generate ID even in genetically uniform populations. This challenges the long-standing view that ID arises exclusively from genetic homozygosity and highlights the need to investigate epigenetic contributions to ID.