Fitness Correlates of Heritable
Variation in Antibody
Responsiveness in a Wild Mammal
A. Graham, A. Hayward, K. Watt, J. Pilkington, J. Pemberton, D. Nussey
Science 2010
Vera Vollenweider
Overview
1. Introduction
• The Immune System
2. Hypothesis
3. Research Questions
4. Methods
5. Results
6. Summary
The Immune System
• Antibodies generated by activated B cells protect the body against
pathogens
• Immune tolerance describes a state of unresponsiveness of the
immune system to self-antigens
• Autoimmunity results from some failure of the host’s immune system
to distinguish self from nonself, causing destruction of self-proteins,
cells, and organs by auto-antibodies
• Antibodies that bind self nuclear and cytoplasmic antigens are called
antinuclear antibodies (ANA)
The Immune System
• Immune systems of different individuals are heterogeneous in the
strength, specificity, and efficacy of responses to infection
• Much of the variation is under genetic control
• Individuals vary in their genetic susceptibility to generate selftargeted immune responses (autoimmunity)
Why has natural selection failed to eliminate alleles that promote
autoimmunity?
Hypothesis
• Individuals with strong immune responses experience fitness benefits
of immunity but are also likely to suffer its costs
• There are trade-offs between antibody-response, survival, and
reproduction
Antibody responses
Reproductive
success
Survival
• Food limitation and high parasite abundance decreases strength and
self-reactivity of immune response
Research Questions
1. Do wild mammals also mount self-directed antibody responses?
2. Do ANA concentrations reflect general antibody responsiveness?
3. Is the variation in ANA concentration among individuals genetically
based?
4. Is there an association between ANAs and different components of
fitness?
Methods
• Unmanaged population of Soay sheep
in Hirta (Scotland)
• Blood plasma samples collected during
August of 11 years:
• 2622 plasma samples
• 1476 sheep
• Measured antinuclear antibodies
(ANAs)
High ANA concentrations
=
strong response to self-antigens
Results I
Do wild mammals also mount self-directed antibody responses?
• Two factors hypothesized to decrease self-reactivity of the immune
system:
• Food limitation
• High parasite abundance
• 114 out of 410 (27.8%) of adult females were positive for ANA
• 21 out of 144 (14.6%) of adult males were positive for ANA
Adult females had significantly higher ANAs than adult
males (P < 0.001)
• ANA concentration increased with age from lambs to adults
Result II
Do ANA concentrations reflect general antibody responsiveness?
• Further immunological analysis with all ANA-positive sheep:
i. Concentrations of total IgG
ii. Concentrations of antibodies to ribonucleoprotein
iii. Concentrations of antibodies to Teladorsagia circumcincta
All positively correlated with ANAs
Result III
Is the variation in ANA concentration among individuals genetically
based?
• A significant proportion of ANA heterogeneity was attributed to
additive genetic effects:
• One-third of the among-individual variation and
• One-eighth of the total phenotypic variance were genetically based
Among-individual variation in ANA concentration is partly
genetically based
Results IV
Is there an association between ANAs and different components of
fitness?
1. Survival
2. Fecundity
1. Survival
Population dynamics characterized
by years of rising and high density
followed by winter crashes
Environment-dependent association
of survival with high ANAs in adult
female sheep
2. Fecundity
Males and females with high ANAs in August were less likely to have
sired or produced a lamb the previous year
Male
Female
Summary
• Positive ANA concentration leads to higher survival rates but reduced
reproduction in female sheep
• Survival-ANA association is environment and sex dependent
• Reduced fecundity in ANA-positive females is accompanied by
improved survival of their neonates
A mechanism for the maintenance of immunoheterogeneity, possibly
including autoimmune susceptibility genes, by natural selection
Density-dependent selection on horn phenotype
T. Clutton-Brock, K. Wilson, I. Stevenson
Phil. Trans. R. Soc. Lond. B 1997
Morphology
Polled
(P)
Scurred
(S)
Normal
(N)
Male
0%
12 %
88 %
Female
41 %
24 %
35 %
Gender
• Development of horn has a
genetic component
• Horn morphology is related
to components of fitness
Morphology
Polled
(P)
Scurred
(S)
Normal
(N)
Male
0%
12 %
88 %
Female
41 %
24 %
35 %
Gender
S male show lower mating
success
Morphology
Polled
(P)
Scurred
(S)
Normal
(N)
Male
0%
12 %
88 %
Female
41 %
24 %
35 %
Gender
S male show lower mating
success
S of both sexes show higher
survival in years when
population density and
mortality are high
Morphology
Gender
Male
Female
S male show lower mating
success
Polled
(P)
Scurred
(S)
Normal
(N)
0%
12 %
88 %
S of both sexes show higher
survival in years when
population density and
mortality are high
35 %
S female show higher
conception rates
41 %
24 %
Density-dependent natural selection acting on simple polymorphic
variation in a free-living population
References
Pictures:
(1)
http://en.wikipedia.org/wiki/Hirta#mediaviewer/File:Outer_Hebrides_UK_relief_location_map.jpg
(2)
soaysheepbreeders.com
(3)
autoimmunityblog.com
(4)
www.roche.com
(5)
http://en.wikipedia.org/wiki/Hirta#mediaviewer/File:Outer_Hebrides_UK_relief_location_map.jpg
(6)
http://en.wikipedia.org/wiki/Shawangunk_Grasslands_National_Wildlife_Refuge#mediaviewer/File:Shawangunk_Grasslands_NWR.
jpg
(7)
http://www.flemingyachts.com/venture3/entry4.html
(8)
http://www.nematode.net/NN3_frontpage.cgi?navbar_selection=speciestable&subnav_selection=Heterodera_schachtii
(9)
http://saltmarshranch.com/about-soay/small-sheep-small-acreage.shtml
(10)
http://markgtelfer.co.uk/2011/05/08/counting-sheep-and-lack-of-sleep/
(11)
http://www.nature.com/hdy/journal/v104/n2/fig_tab/hdy2009109f1.html
Literature
Graham, AL Hayward, AD Watt, KA Pilkington, JG Pemberton, JM Nussey, DHAF Graham, Andrea L. Hayward, Adam D. Watt,
Kathryn A. Pilkington, Jill G. Pemberton, Josephine M. Nussey, Daniel H.TI Fitness Correlates of Heritable Variation in Antibody
Responsiveness in a Wild Mammal, Science 2010
CluttonBrock, TH Wilson, K Stevenson, IRAF CluttonBrock, TH Wilson, K Stevenson, IRTI Density-dependent selection on horn
phenotype in Soay sheep, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCESRI 1997
Moorcroft, P. R., Albon, S. D., Pemberton, J. M., Stevenson, I. R. & Clutton-Brock, T. H. 1996. Densitydependent selection in a fluctuating
ungulate population. Proc. R. Soc. Lond. B263, 31-38