Abstract
Much of our knowledge of the drivers of immune variation, and how these responses vary over time, comes from humans, domesticated livestock or laboratory organisms. While the genetic basis of variation in immune responses have been investigated in these systems, there is a poor understanding of how genetic variation influences immunity in natural, untreated populations living in complex environments. 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 (h2 = 0.21 to 0.57) and highly stable over an individual’s lifespan. 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, 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, and adult IgE levels and lamb IgA and IgG levels were associated with the major histocompatibility complex (MHC). 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.
Highlights
Individual differences in immune responses are widely observed in nature, and are likely to be a major factor underlying variation in disease resistance, health and evolutionary fitness in vertebrates [1]
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
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
Summary
Individual differences in immune responses are widely observed in nature, and are likely to be a major factor underlying variation in disease resistance, health and evolutionary fitness in vertebrates [1]. Efforts to quantify the genetic basis of immunological variation have been largely limited to studies of humans, domesticated livestock and laboratory rodents [4,5,6,7,8]. Experimental studies provide a controlled environment in which to address mechanistic questions about immune function, but offer limited insight into immunological variation under more complex and challenging environmental conditions, as illustrated by dramatic differences in immune phenotypes between wild and laboratory rodents [9,10]. Whilst domesticated livestock and humans are subject to more complex environments, individuals generally receive regular treatment against prevalent infectious agents, which is likely to modify the natural immune response and the contributions of underlying genetic variation. We harness an extensive data set of immune phenotypes and genotypes from an unmanaged and untreated population of Soay sheep to determine the relative contribution of genetic, environmental and individual variation in shaping differences in immunity, and how this varies over the lifetime of individuals
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