FP: LiceRESIST - Unravelling genetic mechanisms underlying sea lice resistance in salmonid fishes

Salmon lice represents the single most economically important animal welfare problem threatening both the sustainability and expansion of salmon aquaculture. In many countries, salmon lice have become multi-resistant to chemical treatment, and the lack of effective treatment against lice threatens future growth in the industry. In the natural environment, the heaviest lice infestations are found on brown trout and Atlantic salmon, with both species displaying weak or absent local inflammatory response and high parasite burden. Unlike these species, some Pacific salmon, particularly coho, have genetic traits that enable them to eliminate sea lice. The genetic mechanisms that give Pacific salmon these advantages are not yet understood. The main objective of the LiceRESIST project is to identify the genes and genome variation responsible for these species differences in resistance, both at the epigenetic and functional level. With a more detailed understanding of the mechanism of lice resistance, it is possible to develop a more resistant Atlantic farmed salmon using precision breeding, which in the long term can improve animal welfare and provide a more sustainable aquaculture industry. So far in the project, we have conducted a challenge test with sea lice (Lepeophtheirus salmonis) in Canada with several salmonid species with different susceptibility to sea lice (Atlantic salmon, rainbow trout, chum, pink, coho). Tissue samples (from skin and fins with and without lice) were sent to Ås and analysed for functional changes (both with respect to gene expression and epigenetic differences). Unfortunately, these analyses revealed poor quality (degradation) in many of the tissue samples. We therefore decided to channel the lab resources towards samples from another challenge trial with lice (Caligus rogercresseyi) conducted under the auspices of AquaGen in Chile. This trial includes the two species with the greatest expected contrast in lice infestation; coho (lowest lice infestation) and Atlantic salmon (highly susceptible to lice). Data from both trials have now been analyzed and we see major differences in gene expression. In particular, genes involved in immune response and wound healing appear to be affected, pointing to these mechanisms as possible reasons for differences in lice infestation in coho and Atlantic salmon. To improve the likelihood of uncovering genomic and/or epigenetic causes of these differences, the project has recently generated a highly improved genome sequence for coho salmon. This genome sequence is now being annotated with functional data (RNA-, ATAC- and ChIP-Seq) from skin, fins and other tissues in coho salmon and compared with annotated genome sequences from Atlantic salmon and rainbow trout to possibly reveal functional differences between the species.

Sea lice (Lepeophtheirus salmonis) is the single greatest biological threat to the development of sustainable salmonid farming. Despite extensive international research efforts, our understanding of the functional genetic basis for host immune responses to sea lice infestations in Atlantic salmon, the main farmed species in Norway, remains unclear, largely due to the complex genetic architecture of the trait. By comparing the functional genomic changes occurring in response to sea lice attack in several salmonid species exhibiting diversity in resistance, LiceRESIST will (i) reveal novel functional mechanisms underlying immunity that have evolved in independent lineages, and (ii) facilitate the identification of key causative genetic variants responsible for lineage-specific resistance to lice burden. Our approach, combining comparative and functional genomics with CRISPR/Cas gene editing for discovery and validation of functional differences, will create opportunities to devise novel therapeutics to combat the sea lice threat. Given the pressing nature of the sea lice problem for aquaculture, in terms of economic losses, animal welfare concerns, and the threat to wild salmon, generating such advanced knowledge as a basis for improved lice management is both urgently required and in full alignment with the vision of the HAVBRUK2 program.