"The accumulation of deleterious mutations and their subsequent effects on fitness play an important role in genome evolution. The mutational load is, however, not distributed evenly across the genome. In particular, genomic regions under strong balancing selection, as well as areas with little recombination are prone to accumulate mutations. In such genomic regions natural selection cannot easily purge the recessive deleterious mutations because they become rarely expressed in homozygote condition, and hence, this mutational load has been dubbed a “sheltered load”. Both the Major Histocompatibility Complex (MHC) of vertebrates and S-locus of plants are thought to carry a large sheltered load which can have important implications for the evolution of both these gene families. However, these research communities have developed their research programmes and theories independently of one another. This proposal brings together both fields for the first time in a truly synergistic collaboration that will investigate several fundamental, and yet unaddressed questions in evolutionary genetics of multigene families. It combines the expertise of the Marie Curie Fellowship applicant (Dr Llaurens) on the evolution of self incompatibility in plants and that of Dr van Oosterhout (University of Hull, UK) on MHC evolution in guppies (Poecilia reticulata). This project aims to empirically characterise the sheltered load in the MHC of guppies by using high-throughput sequencing techniques in collaboration with Prof. Dreyer (Max Planck Institute, Germany). We will furthermore investigate the evolutionary and ecological implications of this MHC-linked sheltered load by using laboratory crosses and field experiments. The comparison between MHC and S-locus evolution will help us to elucidate the population genetic and molecular mechanisms associated with the sheltered load, and solve several longstanding scientific enigmas of the MHC."