Toll-like receptor variation in the bottlenecked population of the Seychelles warbler: Computer simulations see the ‘ghost of selection past’ and quantify the ‘drift debt’

Balancing selection can maintain immunogenetic variation within host populations, but detecting its signal in a post-bottlenecked population is challenging due to the potentially overriding effects of drift. Toll-like receptor genes (TLRs) play a fundamental role in vertebrate immune defence and are predicted to be under balancing selection. We previously characterised variation at TLR loci in the Seychelles warbler (Acrocephalus sechellensis), an endemic passerine that has undergone a historical bottleneck. Five out of seven TLR loci were polymorphic, which is in sharp contrast to the low genome-wide variation observed. However standard population genetic statistical methods failed to detect a contemporary signature of selection at any TLR loci. We examined whether the observed TLR polymorphism could be explained by neutral evolution, simulating the population's demography in the software DIYABC. This showed that the posterior distributions of mutation rates had to be unrealistically high to explain the observed genetic variation. We then conducted simulations with an agent-based model using typical values for the mutation rate, which indicated that weak balancing selection has acted on the three TLR genes. The model was able to detect evidence of past selection elevating TLR polymorphism in the pre-bottleneck populations, but was unable to discern any effects of balancing selection in the contemporary population. Our results show drift is the overriding evolutionary force that has shaped TLR variation in the contemporary Seychelles warbler population, and the observed TLR polymorphisms might be merely the ‘ghost of selection past’. Forecast models predict immunogenetic variation in this species will continue to be eroded in the absence of contemporary balancing selection. Such ‘drift debt’ occurs when a genepool has not yet reached its new equilibrium level of polymorphism, and this loss could be an important threat to many recently bottlenecked populations.