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Major Histocompatibility Complex; Host-parasite co-evolution; mate choice; speciation; three-spined stickleback
Abstract:
Plants and animals share their environments with a rich fauna of parasites and
potentially, there is no species without at least one pathogen. Selection by parasites is
recognized as one of the principal evolutionary processes and has probably even led to the
evolution of sexual reproduction- a major paradox in evolutionary biology.
To counter this constant threat, vertebrates have developed different immune
defenses. In particularly the major histocompatibility complex (MHC) plays an important role in
the vertebrate immune system. MHC molecules present self and non-self peptides to T-cells
and when a foreign peptide is bound it triggers an immune reaction. Since a given MHC
molecule can only present a limited number of different peptides, an immune response can be
initiated against a limited amount of pathogens per MHC allele. Probably due to this limitation
and the immense diversity of parasites, MHC genes present the highest degree of
polymorphism reported in jawed vertebrates. This extreme intra- and inter-individual
polymorphism is thought to be under balancing selection. The mechanisms by which MHC
polymorphism could be maintained are fiercely debated and several theories have been
proposed: heterozygote advantage, negative frequency dependent selection and/or habitat
heterogeneity.
In addition to its puzzling polymorphism, females have been shown to exert MHCdependent
mate choice. Such preference may be better understood in the light of commonly
cited indirect benefits of mate choice including the search for good genes, inbreeding
avoidance and acquisition of resistance genes for the progeny.
In the work detailed in this thesis, I (and my co-authors) used the three-spined stickleback as a
model organism to investigate the role of the MHC in evolution. In an initial study (Chapter I),
we explored whether MHC genes were correlated to important individual fitness traits. While
we found a higher nest quality for males harboring an optimal MHC class IIB diversity, male
breeding coloration was most intense at a maximal MHC class I diversity. Two MHC class I
alleles were identified to be associated with a higher intensity of red coloration. In this study,
we showed that individual sexual displays are MHC-dependent and thus could influence
female mating decision.
It had previously been demonstrated that fish with an intermediate MHC diversity were
better at resisting parasites. Our results from chapter I showed that the MHC affects sexual
characters as well. However, the ultimate measure of evolutionary fitness is the reproductive
success. We combined this knowledge in a field experiment to test the relation between MHC
and reproductive success- the ultimate factor of evolution (Chapter II). Using laboratory-bred
families segregating for MHC genes, we found that reproductive success was higher at
intermediate MHC diversity. In order to test for the generality of this phenomenon, we stocked
the same field enclosures with wild-caught fish (Chapter III). We confirmed that with reference
to their own MHC profile, female sticklebacks preferred to mate with males sharing an
intermediate MHC diversity. Moreover, males with a specific MHC haplotype were better
atresisting a common parasite (Gyrodactylus sp.) and were more likely to be selected by
females. Interestingly, this translated directly into Darwinian fitness since fish harboring this
specific MHC haplotype had a higher reproductive output. We concluded that females based
their mating decision on a specific MHC haplotype conferring resistance against a common
parasite. With this strategy, females achieve a two fold immunogenetic advantage: resistance
against a wide range of parasites while keeping the T-Cell repertoire depletion to a minimum
level and resistance against a currently common and costly parasite. The latter can be
described as “good genes”. Such an interaction between host and parasite driving assortative
mating is a pre-requisite to negative-frequency-dependent selection- a potential mechanism to
explain MHC polymorphism. Our studied not only identified MHC as good genes but also
suggested that females might adopt reproductive strategies that minimize disruption of locally
adapted MHC genes against parasites.
Such results motivated a reflection on the role of host MHC and parasite interaction in
the evolution of population divergence. In chapter IV, we proposed that MHC genes could play
a pleiotropic role in parasite resistance and female mating strategy. Individual MHC diversity is
restricted compared to the entire allele pool due to a low optimal number of MHC loci. In
contrasting niches, parasites communities differ and thus the pools of MHC alleles also differ
between niches since not all alleles can be exhibited. Mate choice for the best adapted MHC
genotype will favor local adaptations and will increase the pace of population differentiation
and speciation. We therefore propose to consider MHC genes as potential “magic traits”.
To investigate the pleiotropic role of MHC genes, we sampled stickleback populations from a
lake and a connected river (chapter V), which previous studies have suggested represent
ecomorphs. The two fish populations harbored different parasite communities. Most probably
as a result of parasite pressure, we found substantial differences in MHC allele pools between
the two ecomorphs. If our predictions are correct, we would expect females to exhibit
assortative mating for males harboring locally adapted MHC alleles. We performed mate
choice experiment based on the genetic component of odor cues, and found that female
preference was directed towards males originating from the same habitat. Again, this suggests
a pleiotropic role of MHC genes through both parasite resistance and mate choice and
reinforces the idea of “magic traits”. Despite a range of observational evidence, no direct
experimental study to date has revealed the connection of locally adapted MHC genes and
local parasites in a natural habitat.
We decided to challenge this question (Chapter VI)and for this test, we crossed three-spined
sticklebacks from the same river and the same lake population as those used in the previous
chapter. The populations displayed almost totally distinct MHC allele pools. Intercrossing F1
hybrids, we obtained a second fish generation segregating into pure river, pure lake and two
hybrid MHC genotypes, while at the same time the genetic background was randomized. We
used a double common garden experiment where fish were exposed simultaneously and
reciprocally into the lake and into the river using replicated cages. We found that MHC
genotypes were not equal in resisting parasites, which resulted in differences in parasite load
between genotypes in turn. The total parasite load harbored by the fish appeared to result from
an adaptive interaction between the innate and the acquired immune system of the hosts,
which were driven by different parasite strategies. Generalist parasites were more successful
in river fish lines, which naturally encounter low infection pressure from these parasites.
However, when confronted with a stickleback specific parasite, which is commonly present in
river habitats, the fish bearing lake MHC genotypes were more infected than fish carrying river
MHC genotypes. In addition, we found support for an additive and synergistic role of genetic
background and innate immunity in parasite resistance. Thus, this first test supports the
adaptive connection between MHC and parasites and reinforces our previous suggestion of
the pleiotropic role of MHC genes.
Eventually, in the last chapter (VII), I report the initial results of another experimental test. We
aimed at testing the potential role of negative frequency dependent selection in maintaining
MHC polymorphism. Our design not only included selection by parasites but also included
female mate choice. We created 6-replicated populations, each formed by 6 different
laboratory-bred families in equal proportions and sex ratio. Three experimental populations
were exposed to Camallanus lacustris, whilst the remaining three were confronted with
Anguillicoloides crassus. These parasites were selected to be present in the original population
were the founders of the lab-bred populations were caught. Letting the system evolve, we
assumed that females would mate with partners that would possess a resistant allele against
the experimental parasite, and thus increase the frequency of this allele in the following
generation. Eggs were collected and raised in the laboratory, and the new stickleback
generation was also exposed to both parasites. We hypothesize that fish from parents that
faced one parasite, e.g. Camallanus lacustris, will be less heavily infected by this parasite than
those derived from parents that encountered Anguillicoloides crassus and vice versa. As this
experiment is running over several stickleback generations, the final dissection of the F2 fish
has not yet taken place. Hence, I report the different steps that have been performed to date.