Quantitative analyses of empirical fitness landscapes

The concept of a fitness landscape is a powerful metaphor that offers insight into various aspects of evolutionary processes and guidance for the study of evolution. Until recently, empirical evidence on the ruggedness of these landscapes was lacking, but since it became feasible to construct all possible genotypes containing combinations of a limited set of mutations, the number of studies has grown to a point where a classification of landscapes becomes possible. The aim of this review is to identify measures of epistasis that allow a meaningful comparison of fitness landscapes and then apply them to the empirical landscapes to discern factors that affect ruggedness. The various measures of epistasis that have been proposed in the literature appear to be equivalent. Our comparison shows that the ruggedness of the empirical landscape is affected by whether the included mutations are beneficial or deleterious and by whether intra- or intergenic epistasis is involved. Finally, the empirical landscapes are compared to landscapes generated with the Rough Mt.\ Fuji model. Despite the simplicity of this model, it captures the features of the experimental landscapes remarkably well.Comment: 24 pages, 5 figures; to appear in Journal of Statistical Mechanics: Theory and Experimen

Seven different genes encode a diverse mixture of isoforms of Bet v 1, the major birch pollen allergen

BACKGROUND: Pollen of the European white birch (Betula pendula, syn. B. verrucosa) is an important cause of hay fever. The main allergen is Bet v 1, member of the pathogenesis-related class 10 (PR-10) multigene family. To establish the number of PR-10/Bet v 1 genes and the isoform diversity within a single tree, PCR amplification, cloning and sequencing of PR-10 genes was performed on two diploid B. pendula cultivars and one interspecific tetraploid Betula hybrid. Sequences were attributed to putative genes based on sequence identity and intron length. Information on transcription was derived by comparison with homologous cDNA sequences available in GenBank/EMBL/DDJB. PCR-cloning of multigene families is accompanied by a high risk for the occurrence of PCR recombination artifacts. We screened for and excluded these artifacts, and also detected putative artifact sequences among database sequences. RESULTS: Forty-four different PR-10 sequences were recovered from B. pendula and assigned to thirteen putative genes. Sequence homology suggests that three genes were transcribed in somatic tissue and seven genes in pollen. The transcription of three other genes remains unknown. In total, fourteen different Bet v 1-type isoforms were identified in the three cultivars, of which nine isoforms were entirely new. Isoforms with high and low IgE-reactivity are encoded by different genes and one birch pollen grain has the genetic background to produce a mixture of isoforms with varying IgE-reactivity. Allergen diversity is even higher in the interspecific tetraploid hybrid, consistent with the presence of two genomes. CONCLUSION: Isoforms of the major birch allergen Bet v 1 are encoded by multiple genes, and we propose to name them accordingly. The present characterization of the Bet v 1 genes provides a framework for the screening of specific Bet v 1 genes among other B. pendula cultivars or Betula species, and for future breeding for trees with a reduced allergenicity. Investigations towards sensitization and immunotherapy should anticipate that patients are exposed to a mixture of Bet v 1 isoforms of different IgE-reactivity, even if pollen originates from a single birch tree

Characterization of PR-10 genes from eight Betula species and detection of Bet v 1 isoforms in birch pollen

<p>Abstract</p> <p>Background</p> <p>Bet v 1 is an important cause of hay fever in northern Europe. Bet v 1 isoforms from the European white birch <it>(Betula pendula) </it>have been investigated extensively, but the allergenic potency of other birch species is unknown. The presence of Bet v 1 and closely related PR-10 genes in the genome was established by amplification and sequencing of alleles from eight birch species that represent the four subgenera within the genus <it>Betula</it>. Q-TOF LC-MS^Ewas applied to identify which PR-10/Bet v 1 genes are actually expressed in pollen and to determine the relative abundances of individual isoforms in the pollen proteome.</p> <p>Results</p> <p>All examined birch species contained several PR-10 genes. In total, 134 unique sequences were recovered. Sequences were attributed to different genes or pseudogenes that were, in turn, ordered into seven subfamilies. Five subfamilies were common to all birch species. Genes of two subfamilies were expressed in pollen, while each birch species expressed a mixture of isoforms with at least four different isoforms. Isoforms that were similar to isoforms with a high IgE-reactivity (Bet v 1a = PR-10.01A01) were abundant in all species except <it>B. lenta</it>, while the hypoallergenic isoform Bet v 1d (= PR-10.01B01) was only found in <it>B. pendula </it>and its closest relatives.</p> <p>Conclusion</p> <p>Q-TOF LC-MS^Eallows efficient screening of Bet v 1 isoforms by determining the presence and relative abundance of these isoforms in pollen. <it>B. pendula </it>contains a Bet v 1-mixture in which isoforms with a high and low IgE-reactivity are both abundant. With the possible exception of <it>B. lenta</it>, isoforms identical or very similar to those with a high IgE-reactivity were found in the pollen proteome of all examined birch species. Consequently, these species are also predicted to be allergenic with regard to Bet v 1 related allergies.</p

Zoning strategies for managing outbreaks of alien plant pests in the European Union: a review

Managing outbreaks of alien plant pests is key to preserving biodiversity and safeguarding crop production. Zoning strategies are applied by plant health authorities to tailor measures to the risk of spread in relation to distance from the outbreak epicentre and the biology of the pest. Here we synthesize information on outbreak management to evaluate the diversity and consistency of such approaches. We collected information on the zoning strategies of 121 outbreaks of 25 plant pests in the European Union (EU). According to the organism’s presence and the measures applied, five zones were distinguished: an infested zone (83% of cases), a buffer zone (76%), a clear-cutting zone (28%), an eradication zone (1%) and a containment zone (1%). Infested zones and buffer zones were adjacent non-overlapping zones, while the clear-cutting zone, eradication zone or containment zone was within either the infested zone or buffer zone. A combination of infested and buffer zones was used in 51% of recorded cases. Measures differed within different zones. Destruction of infested plants in the infested zone was done in 78% of the cases, while surveillance was always applied in the buffer zone. Regulation of an organism at EU level led to a convergence of zoning strategies applied by different member states. Regulations often prescribed the greatest widths used before regulations were issued. Further analyses are needed to explore the efficacy of different strategies including the costs of each strategy. Such analyses should combine insight from practice with bio-economic modelling

Alpha-gliadin genes from the A, B, and D genomes of wheat contain different sets of celiac disease epitopes

BACKGROUND: Bread wheat (Triticum aestivum) is an important staple food. However, wheat gluten proteins cause celiac disease (CD) in 0.5 to 1% of the general population. Among these proteins, the α-gliadins contain several peptides that are associated to the disease. RESULTS: We obtained 230 distinct α-gliadin gene sequences from severaldiploid wheat species representing the ancestral A, B, and D genomes of the hexaploid bread wheat. The large majority of these sequences (87%) contained an internal stop codon. All α-gliadin sequences could be distinguished according to the genome of origin on the basis of sequence similarity, of the average length of the polyglutamine repeats, and of the differences in the presence of four peptides that have been identified as T cell stimulatory epitopes in CD patients through binding to HLA-DQ2/8. By sequence similarity, α-gliadins from the public database of hexaploid T. aestivum could be assigned directly to chromosome 6A, 6B, or 6D. T. monococcum (A genome) sequences, as well as those from chromosome 6A of bread wheat, almost invariably contained epitope glia-α9 and glia-α20, but never the intact epitopes glia-α and glia-α2. A number of sequences from T. speltoides, as well as a number of sequences fromchromosome 6B of bread wheat, did not contain any of the four T cell epitopes screened for. The sequences from T. tauschii (D genome), as well as those from chromosome 6D of bread wheat, were found to contain all of these T cell epitopes in variable combinations per gene. The differences in epitope composition resulted mainly from point mutations. These substitutions appeared to be genome specific. CONCLUSION: Our analysis shows that α-gliadin sequences from the three genomes of bread wheat form distinct groups. The four known T cell stimulatory epitopes are distributed non-randomly across the sequences, indicating that the three genomes contribute differently to epitope content. A systematic analysis of all known epitopes in gliadins and glutenins will lead to better understanding of the differences in toxicity among wheat varieties. On the basis of such insight, breeding strategies can be designed to generate less toxic varieties of wheat which may be tolerated by at least part of the CD patient population

Munc18 and Munc13 regulate early neurite outgrowth

Background information. During development, growth cones of outgrowing neurons express proteins involved in vesicular secretion, such as SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins, Munc13 and Munc18. Vesicles are known to fuse in growth cones prior to synapse formation, which may contribute to outgrowth