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Helena Westerdahl

In silico peptide-binding predictions of MHC class I reveal similarities across distantly related songbird species, suggesting convergence on the level of protein function


Author(s): Westerdahl, H, Follin, E, Karlsson, M, Drews, A, Lundegaard, C, Nielsen, M, Wallin, S, Paulsson, K


Many songbirds have a large number of transcribed MHC class I genes compared to most mammals. To elucidate the reasons for this large number of genes and to search for non-classical MHC genes in songbirds, we compared songbird MHC class I alleles (α1-α3 domains). By applying phylogenetic analysis, homology modelling and in silico peptide-binding predictions, we could compare both functional and genetic relationships among transcribed genes. We found more pronounced clustering of the MHC class I allomorphs (allele-specific proteins) in regard to their protein function (peptide-binding specificities) compared to their genetic relationships (amino acid sequences), indicating that the high number of alleles is of functional significance.

The MHC class I allomorphs from house sparrow and tree sparrow, species that diverged ten MYA, had overlapping peptide-binding specificities. These similarities across species were also confirmed in phylogenetic analyses, and were similar for genes that we interpret as classical and non-classical. Remarkably, there were also overlapping peptide-binding specificities in the allomorphs from house sparrows and great reed warblers, although these species diverged about 30 MYA. This overlap was not found in a tree based on amino acid sequences. Our interpretation is that convergent evolution on the level of the protein function, possibly driven by selection from shared pathogens, has resulted in allomorphs with similar peptide-binding repertoires, although trans-species evolution in combination with gene conversion cannot be excluded.

Jacek Radwan
Jagiellonian University
Institute of Environmental Sciences

Evolution of MHC gene number: optimality hypothesis and beyond


Author(s): Radwan, J


MHC genes code for proteins involved in recognition of pathogens. Their extreme polymorphism, thought to be driven primarily by selection from parasites, has been subject of much theoretical and empirical work. In addition to allelic diversity, MHC genes are often multiplicated, but the evolution of the MHC copy number received relatively less attention. Optimality hypothesis (Nowak et al. 1992) poses that an increase in parasite recognition capabilities with increased number of MHC molecules expressed is traded off against higher rate of deletion of auto-reactive lymphocytes, thus some intermediate individual MHC diversity should be favoured. Empirical tests of this hypothesis have been hampered by technical difficulties associated with the typing of multi-locus genotypes, but this has now been overcome by new generation sequencing methods. I will review the recent empirical studies of the optimality hypothesis. The presence of multiple MHC genes in the genome may also facilitate creation of new alleles via inter-genic recombination (Ohta 1991). The results of simulations of host-parasite coevolution showed that such newly created alleles are very likely to be retained in populations. This opens the possibility for haplotypes with a high number of MHC copies to hitch-hike with positively selected alleles.

Mónica Silva
Faculdade de Ciências, Universidade de Lisboa
Centro de Biologia Ambiental

Evolution of olfaction in tubenose seabirds


Author(s): Silva, MC, Su, Q, Daugherty, S, Coelho, M, Silva, JC


The sense of olfaction is one of the most ancient senses with which vertebrates collect information about their surroundings, playing a critical role in survival and reproduction. We are extending the understanding of the evolution of the olfactory receptor (OR) genes in the avian group, by focusing on Procellariiform seabirds. This group has one of the largest relative olfactory bulb sizes among extant birds, and other anatomical features correlated with high olfactory capability. We built a cosmid library of Cory’s Shearwater (Calonectris diomedea) gDNA, which was screened with partial shearwater OR genes. 96 positive clones were sequenced with a combination of Sanger (cosmid ends), Illumina and 454 sequencing technologies. The resulting hybrid assembly has a cumulative length of 7.4Mb, including 399 unique scaffolds (2.6Mb), and ~ 21K degenerate scaffolds. A total of 144 ORFs (> 75 amino acids) have a significant similarity to OR genes, as determined with HMMs built from bird OR genes. Many are full length OR genes, and provide the basis for a comprehensive study of OR evolution in a lineage that relies extensively on olfaction. Preliminary phylogenetic analyses of shearwater, chicken, zebra finch and lizard OR genes revealed at least three distinct clades in Cory’s Shearwater. A few genes clustered with those of the remaining species in a clade, gamma, that predates the divergence of birds. However, most of the sampled shearwater genes belong to the avian-specific gamma-c clade, within which sequences cluster by species, consistent with a scenario of ubiquitous, lineage-specific expansions and/or the action of concerted evolution. Ongoing analyses will address the evolutionary history and genomic context of OR genes in this avian clade, namely the possible genomic association with MHC genes, as well as sequence diversity within and between clades, in particular in putative ligand-binding pockets encoded by shearwater-specific OR lineages.

Jim Kaufman
University of Cambridge
Department of Pathology
United Kingdom

Gene co-evolution in action: how genomic organisation impacts evolution of the adaptive immune system of jawed vertebrates


Author(s): Kaufman, J


A crucial part of the adaptive immune system of jawed vertebrates is recognition by T lymphocytes of pathogen components presented by molecules of the major histocompatibility complex (MHC). MHC genes often have high levels of allelic polymorphism and sequence diversity, thought to be due to an on-going arms race with pathogens. However, the strong genetic associations of humans are with autoimmune disease. Starting with the chicken MHC as a model, we have found that key features of the MHC genomic organisation and subsequent function differ between typical mammals and many (if not most) non-mammalian vertebrates. In particular, the chicken MHC is organised differently than typical mammals, which leads to haplotypes of polymorphic interacting genes, which in turn leads to single dominantly-expressed MHC class I and class II molecules, which finally leads to strong genetic associations with resistance and susceptibility to infectious pathogens. The salient features discovered for the chicken MHC are shared with many non-mammalian vertebrates and are likely ancestral, with the organisation of the typical mammalian MHC arising from an inversion. However, among jawed vertebrates there are at least two other functional strategies for the MHC which have arisen independently, and still others (like passerine birds) not well understood. The co-evolution between antigen processing and antigen presenting genes should mean that evolution is slower in chickens than in mammals, so we have tried to understand the molecular basis for function in an historic recombinant, and have screened many commercial chickens and other populations for such recombinants.

Christophe Eizaguirre
GEOMAR|Helmholtz Center for Ocean Research
Evolutionary Ecology of Marine Fishes

Genetic signature of local adaptation of MHC genes to varying parasite pressures


Author(s): Eizaguirre, C, Lenz, TL, Kalbe, M, Milinski, M


Although crucial for the understanding of adaptive evolution, genetically resolved examples of local adaptation are rare. To maximize survival and reproduction in their local environment, hosts should resist their local parasites and pathogens. The major histocompatibility complex (MHC) with its key function in parasite resistance represents an ideal candidate to investigate parasite-mediated local adaptation. Using replicated field mesocosms, stocked with second-generation lab-bred three-spined stickleback hybrids of a lake and a river population, we show local adaptation of MHC genotypes to population-specific parasites, independently of the genetic background. Furthermore, the multi-locus specificity of MHC genes revealed that increased individual allele divergence of lake MHC genotypes allows lake fish to fight the broad range of lake parasites, whereas more specific river genotypes confer selective advantages against the less diverse river parasites. Such results demonstrate that not only the presence of given alleles is important for local adaptation but also that the combinations of alleles on the different duplicated loci are crucial for host-parasite coevolution.

Diego Hartasanchez
Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra)
Comparative and Computational Genomics

Interplay of gene conversion and crossover in the molecular evolution of multigene families


Author(s): Hartasanchez, DA, Valles-Codina, O, Navarro, A


Multigene families are part of the pervasive Structural Variation (SV) present in eukaryotic genomes. In humans, regions with SV have been associated to disease and have been shown to participate in evolutionary innovation. Despite its widespread abundance and functional relevance, an accurate description of the underlying forces shaping the evolution of these regions is still lacking. In particular, the proper characterization of the interplay between mutation, crossover and gene conversion in multigene families is fundamental. We have developed a forward-time simulation program that incorporates duplications and focuses on the effect of concerted evolution (the non-independent evolution of duplicated regions). By means of simulations, we have explored a wide range of parameters, gaining insight into the evolution of regions under concerted evolution such as the MHC. First, we observe that neutral concerted evolution can confound scans for selection by mimicking the effects of both weak purifying selection or weak positive selection. These effects can be more pronounced if duplicated regions are collapsed, as is frequent in low-quality genome assemblies. Additionally, we explore the effects of crossover hotspots in duplicated regions that present gene conversion activity. Our results show that multigene-family evolution is highly dependent on the spatial distribution of crossover and gene conversion events and their rates, even under neutrality.

Ludovic Duvaux
University of Sheffield
Animal and Plant Sciences
United Kingdom

Linking chemosensory multigene-family evolution with speciation in the pea aphid (Acyrthosiphon pisum)


Author(s): Duvaux, L, Smadja, C, Ferrari, J, Zhou, J, Butlin, RK


Ludovic DUvaux, Carole Smadja, Julia Ferrari, Within and between species, multigene families (MF) are known to be highly diverse in terms of both Copy Number Variation (CNV) and allelic diversity. Accordingly, within and between population diversities of MF have a strong potential to result from, or to fuel, local adaptation – and possibly speciation. However, these diversities have seldom been contrasted and their relative evolutionary dynamics remain poorly understood. The host-plant races of the pea aphid provide an excellent system to understand these dynamics in the context of speciation with gene flow. Notably, Chemosensory MF (CMF) – e.g. Olfactory Receptors (OR), Gustatory Receptors (GR), Odorant Binding Proteins (OBP) – are critically important for specific host plant recognition, i.e. putatively a main cause of reproductive isolation. We sequenced 120 individuals from 8 races using a target enrichment protocol and Solexa sequencing – guaranteeing a median coverage of 150X. In doing so, we assessed CNV and nucleotidic diversity at about 3000 exons (from CMF, other MF and control genes) and 650 promoters of CMF genes. Preliminary results show CNV is widespread, as it occurs in 65% of all exons (even surprisingly up to 57% for control exons). As with SNPs in single copy genes, most CNV in non CMF genes is shared among races. In contrast, for targets linked to chemosensory genes – notably GR exons and promoters – CNV tends to structure by race. Also, the rate of duplication appears higher for CMF: OR, OBP and promoters show significantly more CNV than other MF. Together, these results suggest that many CMF genes may evolve under positive selection and contribute to adaptation to host plants. In order to better understand the genetic basis of adaptation, work is ongoing to link patterns of CNV (i) to the history of gene flow between races; and (ii) to observed differences in gene expression within and between races across native and non-native host plants.

Jamie Winternitz
Academy of Sciences Czech Republic
Institute of Vertebrate Biology
Czech Republic

Sexual selection more than parasitism explains functional variation of the MHC across mammals


Author(s): Winternitz, JC, Minchey, SG, Garamszegi, LZ, Altizer, SM


Diversity at the major histocompatibility complex (MHC), vitally important for vertebrate immune defense, varies widely across species. Parasites have been identified as a major evolutionary force driving MHC polymorphisms across species, but sexual selection and disassortative mating is another likely mechanism. MHC-based mating preferences have been observed for multiple species including humans, but the generality of mate choice as a driver of MHC polymorphism in the wild is debated. In reality, both parasite-mediated selection and sexual selection may act in concert in wild populations. To investigate potential contributions of parasitism and sexual selection in explaining among-species variation in MHC diversity, we used comparative methods to examine measures of MHC diversity across 115 mammal species, including carnivores, chiroptera, primates, rodents, and ungulates. Specifically, we tested whether parasite species richness and relative testes size (as an indicator of sexual selection) were correlated with two measures of MHC class II DRB diversity: allelic richness and nucleotide diversity. Controlling for mammal phylogeny, neutral mutation rate and confounding ecological variables (i.e. population size, body mass, and sampling effort), we found that parasite species richness was positively correlated with MHC nucleotide diversity for bats and ungulates, and negatively correlated for carnivores. In contrast, relative testes size was positively correlated with MHC nucleotide diversity for carnivores, rodents, and ungulates, and for all taxa combined. Mammal taxonomic group was the strongest predictor of MHC allelic richness, with ungulates having lower diversity in general. This study provides support for both parasite-mediated selection and sexual selection in shaping variation in functional MHC polymorphism across a broad suite of mammals, and importantly, suggests that sexual selection may be more ubiquitous than previously thought.

David Richardson
University of East Anglia
Biological Sciences
United Kingdom

What drives the rapid regeneration of MHC diversity amongst recently bottlenecked populations?


Author(s): Richardson, DS, Van Oosterhout, C, Emerson, BC, Illera, J, Bridgett, S, Gharbi, K, Spurgin, LG


.Population bottlenecks can restrict variation at functional genes, reducing the ability of populations to adapt to new and changing environments. Understanding how populations generate adaptive genetic variation following bottlenecks is therefore central to evolutionary biology. The major histocompatibility complex (MHC) is a multigene family that provides an ideal model for studying adaptive genetic variation due to its central role in pathogen recognition. While de novo MHC sequence variation is generated by point mutation, gene conversion can generate new haplotypes by transferring sections of DNA within and across duplicated MHC loci. However, the extent to which gene conversion generates new MHC haplotypes in wild populations is poorly understood. We used a 454 sequencing protocol to screen MHC variation across all 13 island populations of Berthelot’s pipit (Anthus berthelotii). The recent colonisation of this species (<75,000 years ago), along with the replicated island system gave us a unique opportunity to identify which MHC alleles were involved in the original colonisation events, and which have been generated in situ, post colonisation. This, in turn, allowed us to identify how new MHC haplotypes have been regenerated across the island populations. In light of these results, I will discuss the roles of mutation, gene conversion and selection in generating and maintaining functional genetic diversity in bottlenecked populations.


Chairman: Octávio S. Paulo
Tel: 00 351 217500614 direct
Tel: 00 351 217500000 ext22359
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XIV Congress of the European Society for Evolutionary Biology

Organization Team
Department of Animal Biology (DBA)
Faculty of Sciences of the University of Lisbon
P-1749-016 Lisbon


Computational Biology & Population Genomics Group