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

AbstractHost-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 nematodeTeladorsagia circumcinctain 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.Author 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.

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A genomic region containing RNF212 and CPLX1 is associated with sexually-dimorphic recombination rate variation in Soay sheep (Ovis aries)

10.1101/024869 ◽

2015 ◽

Cited By ~ 5

Author(s):

Susan E. Johnston ◽

Camillo Bérénos ◽

Jon Slate ◽

Josephine M. Pemberton

Keyword(s):

Recombination Rate ◽

Genetic Architecture ◽

Wild Population ◽

Genomic Region ◽

Ovis Aries ◽

Rate Variation ◽

Recombination Rates ◽

Heritable Variation ◽

Soay Sheep ◽

Recombination Rate Variation

ABSTRACTMeiotic recombination breaks down linkage disequilibrium and forms new haplotypes, meaning thatit is an important driver of diversity in eukaryotic genomes. Understanding the causes of variation in recombination rate is important in interpreting and predicting evolutionary phenomena and forunderstanding the potential of a population to respond to selection. However, despite attention inmodel systems, there remains little data on how recombination rate varies at the individual level in natural populations. Here, we used extensive pedigree and high-density SNP information in a wild population of Soay sheep (Ovis aries) to investigate the genetic architecture of individual autosomal recombination rate. Individual rates were high relative to other mammal systems, and were higher in males than in females (autosomal map lengths of 3748 cM and 2860 cM, respectively). The heritability of autosomal recombination rate was low but significant in both sexes(h2 = 0.16 & 0.12 in females and males, respectively). In females, 46.7% of the heritable variation was explained by a sub-telomeric region on chromosome 6; a genome-wide association study showed the strongest associations at the locus RNF212, with further associations observed at a nearby ~374kb region of complete linkage disequilibrium containing three additional candidate loci, CPLX1, GAK and PCGF3. A second region on chromosome 7 containing REC8 and RNF212B explained 26.2% of the heritable variation in recombination rate in both sexes. Comparative analyses with 40 other sheep breeds showed that haplotypes associated with recombination rates are both old and globally distributed. Both regions have been implicated in rate variation in mice, cattle and humans, suggesting a common genetic architecture of recombination rate variation in mammals.AUTHOR SUMMARYRecombination offers an escape from genetic linkage by forming new combinations of alleles, increasing the potential for populations to respond to selection. Understanding the causes and consequences of individual recombination rates are important in studies of evolution and genetic improvement, yet little is known on how rates vary in natural systems. Using data from a wild population of Soay sheep, we show that individual recombination rate is heritable and differs between the sexes, with the majority of genetic variation in females explained by a genomic region containing thegenes RNF212 and CPLX1.

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Conserved Genetic Architecture Underlying Individual Recombination Rate Variation in a Wild Population of Soay Sheep (Ovis aries)

Genetics ◽

10.1534/genetics.115.185553 ◽

2016 ◽

Vol 203 (1) ◽

pp. 583-598 ◽

Cited By ~ 75

Author(s):

Susan E. Johnston ◽

Camillo Bérénos ◽

Jon Slate ◽

Josephine M. Pemberton

Keyword(s):

Recombination Rate ◽

Genetic Architecture ◽

Wild Population ◽

Ovis Aries ◽

Rate Variation ◽

Soay Sheep ◽

Recombination Rate Variation

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The Impact of Environmental Heterogeneity on Genetic Architecture in a Wild Population of Soay Sheep

Genetics ◽

10.1534/genetics.108.086801 ◽

2009 ◽

Vol 181 (4) ◽

pp. 1639-1648 ◽

Cited By ~ 46

Author(s):

Matthew R. Robinson ◽

Alastair J. Wilson ◽

Jill G. Pilkington ◽

Tim H. Clutton-Brock ◽

Josephine M. Pemberton ◽

...

Keyword(s):

Genetic Architecture ◽

Environmental Heterogeneity ◽

Wild Population ◽

Soay Sheep ◽

The Impact

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Sex Differences in Feeding Behaviour at Feeding Station Scale in Soay Sheep (Ovis Aries)

Behaviour ◽

10.1163/1568539042360143 ◽

2004 ◽

Vol 141 (8) ◽

pp. 999-1020 ◽

Cited By ~ 7

Author(s):

◽

Keyword(s):

Feeding Behaviour ◽

Ovis Aries ◽

Intake Rate ◽

Same Sex ◽

Soay Sheep ◽

Food Items ◽

Feeding Station ◽

Foraging Decisions ◽

Mouth Size ◽

Mechanistic Response

AbstractHerbivorous ungulates live in a spatially heterogeneous environment making foraging decisions at a range of hierarchical scales, from bite size to landscape. We investigated the factors that control intake rate in Soay sheep (Ovis aries) when discrete items of food were sparsely distributed at the feeding station scale. Within the feeding station we varied the difficulty of accessing food, distance between items of food, difficulty of finding the food and complexity of the feeding station and recorded how intake rate responded in relation to body size, mouth size and the sex of the animal. Our findings demonstrated how increasing difficulty of accessing food, and increasing complexity of the feeding station negatively affected intake rate. The expected mechanistic response that smaller animals or animals with smaller mouth size were better at handling discrete small items of food, was overridden by individual and sexual differences in behaviour. We also considered that intake rate within a feeding station could be maximised by optimising the spatial pattern of offtake, and the results clearly indicated that both sexes tended to show clustered patterns of offtake. Animals of the same sex responded in a similar way to the difficulty in handling food items; males persevered more than females and consequently were less handicaped by having larger mouths. We discussed these results in relation to behavioural and body mass differences between the sexes and animals.

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Unexpected heterozygosity in an island mouflon population founded by a single pair of individuals

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2006.3743 ◽

2006 ◽

Vol 274 (1609) ◽

pp. 527-533 ◽

Cited By ~ 57

Author(s):

Renaud Kaeuffer ◽

David W Coltman ◽

Jean-Louis Chapuis ◽

Dominique Pontier ◽

Denis Réale

Keyword(s):

Genetic Diversity ◽

Wild Population ◽

Ovis Aries ◽

Stochastic Simulations ◽

Single Pair ◽

Small Populations ◽

Short Period ◽

Large Populations ◽

History Of ◽

Over Time

In population and conservation genetics, there is an overwhelming body of evidence that genetic diversity is lost over time in small populations. This idea has been supported by comparative studies showing that small populations have lower diversity than large populations. However, longitudinal studies reporting a decline in genetic diversity throughout the whole history of a given wild population are much less common. Here, we analysed changes in heterozygosity over time in an insular mouflon ( Ovis aries ) population founded by two individuals in 1957 and located on one of the most isolated locations in the world: the Kerguelen Sub-Antarctic archipelago. Heterozygosity measured using 25 microsatellite markers has actually increased over 46 years since the introduction, and exceeds the range predicted by neutral genetic models and stochastic simulations. Given the complete isolation of the population and the short period of time since the introduction, changes in genetic variation cannot be attributed to mutation or migration. Several lines of evidence suggest that the increase in heterozygosity with time may be attributable to selection. This study shows the importance of longitudinal genetic surveys for understanding the mechanisms that regulate genetic diversity in wild populations.

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A Comparative Overview of the Intracellular Guardians of Plants and Animals: NLRs in Innate Immunity and Beyond

Annual Review of Plant Biology ◽

10.1146/annurev-arplant-080620-104948 ◽

2021 ◽

Vol 72 (1) ◽

Author(s):

Zane Duxbury ◽

Chih-hang Wu ◽

Pingtao Ding

Keyword(s):

Immune Responses ◽

Genetic Architecture ◽

Pathogen Detection ◽

Current Knowledge ◽

Plant Immunity ◽

Innate Immune ◽

Plant Biology ◽

Annual Review ◽

Publication Date ◽

Nucleotide Binding Domain

Nucleotide-binding domain leucine-rich repeat receptors (NLRs) play important roles in the innate immune systems of both plants and animals. Recent breakthroughs in NLR biochemistry and biophysics have revolutionized our understanding of how NLR proteins function in plant immunity. In this review, we summarize the latest findings in plant NLR biology and draw direct comparisons to NLRs of animals. We discuss different mechanisms by which NLRs recognize their ligands in plants and animals. The discovery of plant NLR resistosomes that assemble in a comparable way to animal inflammasomes reinforces the striking similarities between the formation of plant and animal NLR complexes. Furthermore, we discuss the mechanisms by which plant NLRs mediate immune responses and draw comparisons to similar mechanisms identified in animals. Finally, we summarize the current knowledge of the complex genetic architecture formed by NLRs in plants and animals and the roles of NLRs beyond pathogen detection. Expected final online publication date for the Annual Review of Plant Biology, Volume 72 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Epidemiology of nematode infections of Soay sheep (Ovis aries L.) on St Kilda

Parasitology ◽

10.1017/s0031182000074667 ◽

1992 ◽

Vol 105 (3) ◽

pp. 481-492 ◽

Cited By ~ 69

Author(s):

F. M. D. Gulland ◽

M. Fox

Keyword(s):

Population Density ◽

Infection Intensity ◽

Host Population ◽

Ovis Aries ◽

Sheep Population ◽

Soay Sheep ◽

Infective Larvae ◽

Population Crash ◽

Faecal Egg Counts ◽

Bad Weather

SUMMARYThe epidemiology of nematode infections of Soay sheep on the island of St Kilda over a period of 2 years (August 1988–August 1990) spanning a host population crash is described. Infective larvae (L3) levels on pasture were high (2422±365 L3/kg D.M. grass in midsummer 1988) when host population density was high, decreasing after the sheep population declined by 70% in early 1989 (601 ±14 L3/kg D.M. in midsummer 1989). The availability of infective larvae to sheep increased during the winter of 1988–1989, probably as a result of concentration of existing larvae on grass as vegetation was destroyed by bad weather and overgrazing. Increased availability of pre-parasitic stages was accompanied by a marked increased in faecal egg counts from sheep of all ages and both sexes. Prevalence and intensity of infection (faecal egg counts) were higher in males than females throughout the 2-year study (χ2 = 208.3, P < 0.005 and F1.2000 = 304, P < 0.001 respectively), except during the lambing periods, and decreased with age in both sexes. Changes in prevalence and intensity of strongyle infections were associated with changes in host population density. Prevalence and intensity of Dictyocaulus filaria larvae in faeces increased during the host population crash. Infection intensity decreased with age (F1.203 = 44.02, P < 0.001) and was higher in males than females (F1.203 = 13.45, P < 0.001).

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Genetic architecture and lifetime dynamics of inbreeding depression in a wild mammal

10.1101/2020.05.27.118877 ◽

2020 ◽

Cited By ~ 3

Author(s):

M.A. Stoffel ◽

S.E. Johnston ◽

J.G. Pilkington ◽

J.M Pemberton

Keyword(s):

Life History ◽

Inbreeding Depression ◽

Genetic Architecture ◽

Rate Variation ◽

Wild Mammal ◽

Annual Survival ◽

Soay Sheep ◽

Genome Wide ◽

A Genome ◽

Recombination Rate Variation

AbstractInbreeding depression is a phenomenon of long-standing importance, but we know surprisingly little about its genetic architecture, precise effects and life-history dynamics in wild populations. Here, we combined 417K imputed SNP genotypes for 5952 wild Soay sheep with detailed long-term life-history data to explore inbreeding depression on a key fitness component, annual survival. Inbreeding manifests in long runs of homozygosity (ROH) and these are abundant in Soay sheep, covering on average 24% of the autosomal genome and up to 50% in the most inbred individuals. The ROH landscape is shaped by recombination rate variation and differs widely across the genome, including islands where up to 87% of the population have an ROH and deserts where the ROH prevalence is as low as 4%. We next quantified individual inbreeding as the proportion of the autosomal genome in ROH (FROH) and estimated its effect on annual survival. The consequences of inbreeding are severe; a 10% increase in FROH was associated with a 68% [95% CI 55-78%] decrease in the odds of survival. However, the strength of inbreeding depression is dynamic across the lifespan. We estimate depression to peak in young adults, to decrease into older ages and to be weaker in lambs, where inbreeding effects are possibly buffered by maternal care. Finally, using a genome-wide association scan on ROH, we show that inbreeding causes depression predominantly through many loci with small effects, but we also find three regions in the genome with putatively strongly deleterious mutations. Our study reveals population and genome-wide patterns of homozygosity caused by inbreeding and sheds light on the strength, dynamics and genetic architecture of inbreeding depression in a wild mammal population.

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Haplotyping MHC class IIa by high throughput screening in an isolated sheep population

10.1101/2020.07.20.212225 ◽

2020 ◽

Author(s):

K.L. Dicks ◽

J.M. Pemberton ◽

K.T. Ballingall ◽

S.E. Johnston

Keyword(s):

High Throughput Screening ◽

Population Data ◽

Ovis Aries ◽

Island Population ◽

Sheep Population ◽

Soay Sheep ◽

Histocompatibility Complex ◽

Content Variation ◽

Sanger Sequence ◽

Polymorphic Gene

AbstractInvestigating the current evolutionary processes acting on a highly polymorphic gene region, such as the major histocompatibility complex (MHC), requires extensive population data for both genotypes and phenotypes. The MHC consists of several tightly linked loci with both allelic and gene content variation, making it challenging to genotype. Eight class IIa haplotypes have previously been identified in the Soay sheep (Ovis aries) of St. Kilda using Sanger sequencing and cloning, but no single locus is representative of all haplotypes. Here, we exploit the closed nature of the island population of Soay sheep and its limited haplotypic variation to identify a panel of SNPs that enable imputation of MHC haplotypes. We compared MHC class IIa haplotypes determined by Sanger sequence-based genotyping of 135 individuals to their SNP profiles generated using the Ovine Infinium HD BeadChip. A panel of 11 SNPs could reliably determine MHC diplotypes, and two additional SNPs within the DQA1 gene enabled detection of a recombinant SNP haplotype. The panel of 13 SNPs was genotyped in 5951 sheep, of which 5349 passed quality control. Using the Soay sheep pedigree, we were able to trace the origin and inheritance of a recombinant SNP haplotype.

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