The genetic architecture of helminth-specific immune responses in a wild population of Soay sheep (Ovis aries)

Abstract

Host-parasite interactions are powerful drivers of evolutionary and ecological dynamics in natural populations. Variation in immune responses to infection is likely to shape the outcome of these interactions, with important consequences for the fitness of both host and parasite. However, little is known about how genetic variation contributes to variation in immune responses under natural conditions. Here, we examine the genetic architecture of variation in immune traits in the Soay sheep of St Kilda, an unmanaged population of sheep infected with strongyle gastrointestinal nematodes. We assayed IgA, IgE and IgG antibodies against the prevalent nematode Teladorsagia circumcincta in the blood plasma of > 3,000 sheep collected over 26 years. Antibody levels were significantly heritable, ranging from 0.21 to 0.39 in lambs and from 0.23 to 0.57 in adults. IgA levels were strongly associated with a region on chromosome 24 explaining 21.1% and 24.5% of heritable variation in lambs and adults, respectively; this region was adjacent to two candidate loci, the Class II Major Histocompatibility Complex Transactivator (CIITA) and C-Type Lectin Domain Containing 16A (CLEC16A). Lamb IgA levels were also associated with the immunoglobulin heavy constant loci (IGH) complex on chromosome 18. Adult IgE levels and lamb IgG levels were associated with the major histocompatibility complex (MHC) on chromosome 20. This study provides evidence of high heritability of a complex immunological trait under natural conditions and provides the first evidence from a genome-wide study that large effect genes located outside the MHC region exist for immune traits in the wild.\n\nAuthor summaryHost-parasite interactions are powerful drivers of evolutionary and ecological dynamics in natural populations. Variation in immune responses to infection shapes the outcome of these interactions, with important consequences for the ability of the host and parasite to survive and reproduce. However, little is known about how much genes contribute to variation in immune responses under natural conditions. Our study investigates the genetic architecture of variation in three antibody types, IgA, IgE and IgG in a wild population of Soay sheep on the St Kilda archipelago in North-West Scotland. Using data collected over 26 years, we show that antibody levels have a heritable basis in lambs and adults and are stable over lifetime of individuals. We also identify several genomic regions with large effects on immune responses. Our study offers the first insights into the genetic control of immunity in a wild population, which is essential to understand how immune profiles vary in challenging natural conditions and how natural selection maintains genetic variation in complex immune traits.