Biological Sciences, Department of

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A Survey of Putative Secreted and Transmembrane Proteins Encoded in the C. elegans Genome

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2012
Abstract: 

Background: Almost half of the Caenorhabditis elegans genome encodes proteins with either a signal peptide or atransmembrane domain. Therefore a substantial fraction of the proteins are localized to membranes, reside in thesecretory pathway or are secreted. While these proteins are of interest to a variety of different researchers rangingfrom developmental biologists to immunologists, most of secreted proteins have not been functionallycharacterized so far.Results: We grouped proteins containing a signal peptide or a transmembrane domain using various criteriaincluding evolutionary origin, common domain organization and functional categories. We found that putativesecreted proteins are enriched for small proteins and nematode-specific proteins. Many secreted proteins arepredominantly expressed in specific life stages or in one of the two sexes suggesting stage- or sex-specificfunctions. More than a third of the putative secreted proteins are upregulated upon exposure to pathogens,indicating that a substantial fraction may have a role in immune response. Slightly more than half of thetransmembrane proteins can be grouped into broad functional categories based on sequence similarity to proteinswith known function. By far the largest groups are channels and transporters, various classes of enzymes andputative receptors with signaling function.Conclusion: Our analysis provides an overview of all putative secreted and transmembrane proteins in C. elegans.This can serve as a basis for selecting groups of proteins for large-scale functional analysis using reverse geneticapproaches.

Document type: 
Article

IgCAMs Redundantly Control Axon Navigation in Caenorhabditis elegans

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2009
Abstract: 

Background: Cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) form one ofthe largest and most diverse families of adhesion molecules and receptors in the nervous system.Many members of this family mediate contact and communication among neurons duringdevelopment. The Caenorhabditis elegans genome contains a comparatively small number ofIgCAMs, most of which are evolutionarily conserved and found across all animal phyla. Only someof these have been functionally characterized so far.Results: We systematically analyzed previously uncharacterized IgCAMs in C. elegans. Greenfluorescent protein reporter constructs of 12 IgCAMs revealed that expression generally is notconfined to a single tissue and that all tissues express at least one of the IgCAMs. Most IgCAMswere expressed in neurons. Within the nervous system significant overlap in expression was foundin central components of the motor circuit, in particular the command interneurons, ventral cordmotoneurons as well as motoneurons innervating head muscles. Sensory neurons areunderrepresented among the cells expressing these IgCAMs. We isolated mutations for eight ofthe genes showing neuronal expression. Phenotypic analysis of single mutants revealed limitedneuronal defects, in particular axon navigation defects in some of the mutants. Systematic geneticinteraction studies uncovered two cases of functional overlap among three and four genes,respectively. A strain combining mutations in all eight genes is viable and shows no additionaldefects in the neurons that were analyzed, suggesting that genetic interactions among those genesare limited.Conclusion: Genetic interactions involving multiple IgCAMs affecting axon outgrowthdemonstrate functional overlap among IgCAMs during nervous system development.

Document type: 
Article

An Experimental Test for Indirect Benefits in Drosophila melanogaster

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2007
Abstract: 

Background: Despite much empirical attention, tests for indirect benefits of mate choice haverarely considered the major components of sexual and nonsexual offspring fitness relevant to apopulation. Here we use a novel experimental design to test for the existence of any indirectbenefits in a laboratory adapted population of D. melanogaster. Our experiment compared thefitness (mating success, longevity, and productivity) of individuals possessing genomes that derivedtwo generations previously from males that were either entirely successful (studs) or whollyunsuccessful (duds) at achieving mates in three subsequent rounds of mating trials.Results: Males from the stud treatment were 30% more successful on average at securing matesthan males from the dud treatment. In contrast, we found no difference between treatments inmeasures of productivity or of longevity when measured in a mixed-sex environment. In theabsence of females, however, males in the stud treatment outlived males in the dud treatment.Conclusion: Our results suggest that mating with successful males in this population provides anindirect benefit to females and that, at least in this environment, the benefit arises primarily throughthe production of more attractive male offspring. However, it is unclear whether this representssolely a traditional sexy sons benefit or whether there is an additional good genes component (withmale offspring simply allocating their surplus condition to traits that enhance their mating success).The lack of any detectable differences in female fitness between the two treatments suggests theformer, although the longevity advantage of males in the stud treatment when females were absentis consistent with the latter. Determining the effect of this indirect benefit on the evolution offemale mate preferences (or resistance) will require comparable data on the direct costs of matingwith various males, and an understanding of how these costs and benefits integrate acrossgenerations and vary among environments.

Document type: 
Article

Shigella Flexneri Utilize the Spectrin Cytoskeleton during Invasion and Comet Tail Generation

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2012
Abstract: 

Background: The spectrin cytoskeleton is emerging as an important host cell target of enteric bacterial pathogens.Recent studies have identified a crucial role for spectrin and its associated proteins during key pathogenicprocesses of Listeria monocytogenes and Salmonella Typhimurium infections. Here we investigate the involvementof spectrin cytoskeletal components during the pathogenesis of the invasive pathogen Shigella flexneri.Results: Immunofluorescent microscopy reveals that protein 4.1 (p4.1), but not adducin or spectrin, is robustlyrecruited to sites of S. flexneri membrane ruffling during epithelial cell invasion. Through siRNA-mediatedknockdowns, we identify an important role for spectrin and the associated proteins adducin and p4.1 during S.flexneri invasion. Following internalization, all three proteins are recruited to the internalized bacteria, howeverupon generation of actin-rich comet tails, we observed spectrin recruitment to those structures in the absence ofadducin or p4.1.Conclusion: These findings highlight the importance of the spectrin cytoskeletal network during S. flexneripathogenesis and further demonstrate that pathogenic events that were once thought to exclusively recruit theactin cytoskeletal system require additional cytoskeletal networks.

Document type: 
Article

Ecological Transcriptomics of Lake-Type and Riverine Sockeye Salmon (Oncorhynchus nerka)

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2011
Abstract: 

Background: There are a growing number of genomes sequenced with tentative functions assigned to a largeproportion of the individual genes. Model organisms in laboratory settings form the basis for the assignment ofgene function, and the ecological context of gene function is lacking. This work addresses this shortcoming byinvestigating expressed genes of sockeye salmon (Oncorhynchus nerka) muscle tissue. We compared morphologyand gene expression in natural juvenile sockeye populations related to river and lake habitats. Based on previouslydocumented divergent morphology, feeding strategy, and predation in association with these distinctenvironments, we expect that burst swimming is favored in riverine population and continuous swimming isfavored in lake-type population. In turn we predict that morphology and expressed genes promote burstswimming in riverine sockeye and continuous swimming in lake-type sockeye.Results: We found the riverine sockeye population had deep, robust bodies and lake-type had shallow,streamlined bodies. Gene expression patterns were measured using a 16K microarray, discovering 141 genes withsignificant differential expression. Overall, the identity and function of these genes was consistent with ourhypothesis. In addition, Gene Ontology (GO) enrichment analyses with a larger set of differentially expressed genesfound the “biosynthesis” category enriched for the riverine population and the “metabolism” category enriched forthe lake-type population.Conclusions: This study provides a framework for understanding sockeye life history from a transcriptomicperspective and a starting point for more extensive, targeted studies determining the ecological context of genes.

Document type: 
Article

Characterization of the Astacin Family of Metalloproteases in C. elegans

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2010
Abstract: 

Background: Astacins are a large family of zinc metalloproteases found in bacteria and animals. They have diverseroles ranging from digestion of food to processing of extracellular matrix components. The C. elegans genomecontains an unusually large number of astacins, of which the majority have not been functionally characterized yet.Results: We analyzed the expression pattern of previously uncharacterized members of the astacin family to tryand obtain clues to potential functions. Prominent sites of expression for many members of this family are thehypodermis, the alimentary system and several specialized cells including sensory sheath and sockets cells, whichare located at openings in the body wall. We isolated mutants affecting representative members of the varioussubfamilies. Mutants in nas-5, nas-21 and nas-39 (the BMP-1/Tolloid homologue) are viable and have no apparentphenotypic defects. Mutants in nas-6 and nas-6; nas-7 double mutants are slow growing and have defects in thegrinder of the pharynx, a cuticular structure important for food processing.Conclusions: Expression data and phenotypic characterization of selected family members suggest a diversity offunctions for members of the astacin family in nematodes. In part this might be due to extracellular structuresunique to nematodes.

Document type: 
Article

Computing Evolutionary Distinctiveness Indices in Large Scale Analysis

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2012
Abstract: 

We present optimal linear time algorithms for computing the Shapley values and ‘heightened evolutionarydistinctiveness’ (HED) scores for the set of taxa in a phylogenetic tree. We demonstrate the efficiency of these newalgorithms by applying them to a set of 10,000 reasonable 5139-species mammal trees. This is the first time theseindices have been computed on such a large taxon and we contrast our finding with an ad-hoc index formammals, fair proportion (FP), used by the Zoological Society of London’s EDGE programme. Our empirical resultsfollow expectations. In particular, the Shapley values are very strongly correlated with the FP scores, but provide ahigher weight to the few monotremes that comprise the sister to all other mammals. We also find that the HEDscore, which measures a species’ unique contribution to future subsets as function of the probability that closerelatives will go extinct, is very sensitive to the estimated probabilities. When they are low, HED scores are less thanFP scores, and approach the simple measure of a species’ age. Deviations (like the Solendon genus of the WestIndies) occur when sister species are both at high risk of extinction and their clade roots deep in the tree.Conversely, when endangered species have higher probabilities of being lost, HED scores can be greater than FPscores and species like the African elephant Loxondonta africana, the two solendons and the thumbless batFuripterus horrens can move up the rankings. We suggest that conservation attention be applied to such speciesthat carry genetic responsibility for imperiled close relatives. We also briefly discuss extensions of Shapley valuesand HED scores that are possible with the algorithms presented here.

Document type: 
Article

Evolution and Connectivity in the World-Wide Migration System of the Mallard: Inferences from Mitochondrial DNA

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2011
Abstract: 

Background: Main waterfowl migration systems are well understood through ringing activities. However, inmallards (Anas platyrhynchos) ringing studies suggest deviations from general migratory trends and traditions inwaterfowl. Furthermore, surprisingly little is known about the population genetic structure of mallards, andstudying it may yield insight into the spread of diseases such as Avian Influenza, and in management andconservation of wetlands. The study of evolution of genetic diversity and subsequent partitioning thereof duringthe last glaciation adds to ongoing discussions on the general evolution of waterfowl populations and flywayevolution. Hypothesised mallard flyways are tested explicitly by analysing mitochondrial mallard DNA from thewhole northern hemisphere.Results: Phylogenetic analyses confirm two mitochondrial mallard clades. Genetic differentiation within Eurasia andNorth-America is low, on a continental scale, but large differences occur between these two land masses (FST =0.51). Half the genetic variance lies within sampling locations, and a negligible portion between currentlyrecognised waterfowl flyways, within Eurasia and North-America. Analysis of molecular variance (AMOVA) atcontinent scale, incorporating sampling localities as smallest units, also shows the absence of population structureon the flyway level. Finally, demographic modelling by coalescence simulation proposes a split between Eurasiaand North-America 43,000 to 74,000 years ago and strong population growth (~100fold) since then and littlemigration (not statistically different from zero).Conclusions: Based on this first complete assessment of the mallard’s world-wide population genetic structure weconfirm that no more than two mtDNA clades exist. Clade A is characteristic for Eurasia, and clade B for North-America although some representatives of clade A are also found in North-America. We explain this pattern byevaluating competing hypotheses and conclude that a complex mix of historical, recent and anthropogenic factorsshaped the current mallard populations. We refute population classification based on flyways proposed byornithologists and managers, because they seem to have little biological meaning. Our results have implications forwetland management and conservation, with special regard to the release of farmed mallards for hunting, as wellas for the possible transmission of Avian Influenza by mallards due to migration.

Document type: 
Article

Widespread Horizontal Genomic Exchange does not Erode Species Barriers among Sympatric Ducks

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2012
Abstract: 

Background: The study of speciation and maintenance of species barriers is at the core of evolutionary biology.During speciation the genome of one population becomes separated from other populations of the same species,which may lead to genomic incompatibility with time. This separation is complete when no fertile offspring isproduced from inter-population matings, which is the basis of the biological species concept. Birds, in particularducks, are recognised as a challenging and illustrative group of higher vertebrates for speciation studies. There aremany sympatric and ecologically similar duck species, among which fertile hybrids occur relatively frequently innature, yet these species remain distinct.Results: We show that the degree of shared single nucleotide polymorphisms (SNPs) between five species ofdabbling ducks (genus Anas) is an order of magnitude higher than that previously reported between any pair ofeukaryotic species with comparable evolutionary distances. We demonstrate that hybridisation has led to sustainedexchange of genetic material between duck species on an evolutionary time scale without disintegrating speciesboundaries. Even though behavioural, genetic and ecological factors uphold species boundaries in ducks, wedetect opposing forces allowing for viable interspecific hybrids, with long-term evolutionary implications. Based onthe superspecies concept we here introduce the novel term “supra-population” to explain the persistence of SNPsidentical by descent within the studied ducks despite their history as distinct species dating back millions of years.Conclusions: By reviewing evidence from speciation theory, palaeogeography and palaeontology we propose afundamentally new model of speciation to accommodate our genetic findings in dabbling ducks. This model, weargue, may also shed light on longstanding unresolved general speciation and hybridisation patterns in higherorganisms, e.g. in other bird groups with unusually high hybridisation rates. Observed parallels to horizontal genetransfer in bacteria facilitate the understanding of why ducks have been such an evolutionarily successful group ofanimals. There is large evolutionary potential in the ability to exchange genes among species and the resultingdramatic increase of effective population size to counter selective constraints.

Document type: 
Article

Evolution of Embryonic Developmental Period in the Marine Bird Families Alcidae and Spheniscidae: Roles for Nutrition and Predation?

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2010
Abstract: 

Background: Nutrition and predation have been considered two primary agents of selection important in theevolution of avian life history traits. The relative importance of these natural selective forces in the evolution of avianembryonic developmental period (EDP) remain poorly resolved, perhaps in part because research has tended to focuson a single, high taxonomic-level group of birds: Order Passeriformes. The marine bird families Alcidae (auks) andSpheniscidae (penguins) exhibit marked variation in EDP, as well as behavioural and ecological traits ultimately linkedto EDP. Therefore, auks and penguins provide a unique opportunity to assess the natural selective basis of variation in akey life-history trait at a low taxonomic-level. We used phylogenetic comparative methods to investigate the relativeimportance of behavioural and ecological factors related to nutrition and predation in the evolution of avian EDP.Results: Three behavioural and ecological variables related to nutrition and predation risk (i.e., clutch size, activitypattern, and nesting habits) were significant predictors of residual variation in auk and penguin EDP based on modelspredicting EDP from egg mass. Species with larger clutch sizes, diurnal activity patterns, and open nests hadsignificantly shorter EDPs. Further, EDP was found to be longer among birds which forage in distant offshore waters,relative to those that foraged in near shore waters, in line with our predictions, but not significantly so.Conclusion: Current debate has emphasized predation as the primary agent of selection driving avian life historydiversification. Our results suggest that both nutrition and predation have been important selective forces in theevolution of auk and penguin EDP, and highlight the importance of considering these questions at lower taxonomicscales. We suggest that further comparative studies on lower taxonomic-level groups will continue to constructivelyinform the debate on evolutionary determinants of avian EDP, as well as other life history parameters.

Document type: 
Article