Whole genomes reveal multiple candidate genes and pathways involved in the immune response of dolphins to a highly infectious virus.

Wildlife species are challenged by various infectious diseases that act as important demographic drivers of populations and have become a great conservation concern particularly under growing environmental changes. The new era of whole genome sequencing provides new opportunities and avenues to explore the role of genetic variants in the plasticity of immune responses, particularly in non-model systems. Cetacean morbillivirus (CeMV) has emerged as a major viral threat to cetacean populations worldwide, contributing to the death of thousands of individuals of multiple dolphin and whale species. To understand the genomic basis of immune responses to CeMV, we generated and analysed whole genomes of 53 Indo-Pacific bottlenose dolphins (Tursiops aduncus) exposed to Australia's largest known CeMV-related mortality event that killed at least 50 dolphins from three different species. The genomic data set consisted of 10,168,981 SNPs anchored onto 23 chromosome-length scaffolds and 77 short scaffolds. Whole genome analysis indicated that levels of inbreeding in the dolphin population did not influence the outcome of an individual. Allele frequency estimates between survivors and nonsurvivors of the outbreak revealed 15,769 candidate SNPs, of which 689 were annotated to 295 protein coding genes. These included 50 genes with functions related to innate and adaptive immune responses, and cytokine signalling pathways and genes thought to be involved in immune responses to other morbilliviruses. Our study characterised genomic regions and pathways that may contribute to CeMV immune responses in dolphins. This represents a stride towards clarifying the complex interactions of the cetacean immune system and emphasises the value of whole genome data sets in understanding genetic elements that are essential for species conservation, including disease susceptibility and adaptation.

Genome-wide association study of an unusual dolphin mortality event reveals candidate genes for susceptibility and resistance to cetacean morbillivirus.

Infectious diseases are significant demographic and evolutionary drivers of populations, but studies about the genetic basis of disease resistance and susceptibility are scarce in wildlife populations. Cetacean morbillivirus (CeMV) is a highly contagious disease that is increasing in both geographic distribution and incidence, causing unusual mortality events (UME) and killing tens of thousands of individuals across multiple cetacean species worldwide since the late 1980s. The largest CeMV outbreak in the Southern Hemisphere reported to date occurred in Australia in 2013, where it was a major factor in a UME, killing mainly young Indo-Pacific bottlenose dolphins (Tursiops aduncus). Using cases (nonsurvivors) and controls (putative survivors) from the most affected population, we carried out a genome-wide association study to identify candidate genes for resistance and susceptibility to CeMV. The genomic data set consisted of 278,147,988 sequence reads and 35,493 high-quality SNPs genotyped across 38 individuals. Association analyses found highly significant differences in allele and genotype frequencies among cases and controls at 65 SNPs, and Random Forests conservatively identified eight as candidates. Annotation of these SNPs identified five candidate genes (MAPK8, FBXW11, INADL, ANK3 and ACOX3) with functions associated with stress, pain and immune responses. Our findings provide the first insights into the genetic basis of host defence to this highly contagious disease, enabling the development of an applied evolutionary framework to monitor CeMV resistance across cetacean species. Biomarkers could now be established to assess potential risk factors associated with these genes in other CeMV-affected cetacean populations and species. These results could also possibly aid in the advancement of vaccines against morbilliviruses.