Biology ePrints

Permanent URI for this collectionhttps://digital.lib.washington.edu/handle/1773/4620

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WikiDust: a TinkerCell Plugin to Annotate and Share Network Models
(2011) Johnson, Jeffrey; Sauro, Herbert M.; Chandran, Deepak; Galdzicki, Michal
We present WikiDust, a software tool that (a) facilitates searches for DNA components, and (b) produces annotated webready images for improved sharing of designs. WikiDust is a plugin for TinkerCell, a CAD design tool for genetic regulatory networks. WikiDust leverages the SBOL standard to connect TinkerCell to the Registry of Standard Biological Parts. Using standard languages and components facilitates efficient communication and reuse of models. Availability: WikiDust is available through TinkerCell’s automatic plugin installation feature. TinkerCell can be downloaded from http://www.tinkercell.com, and source code for WikiDust can be found at http://www.tinkercell.com/plugins/
Survey of Shell-boring Microorganisms Across a Depth Gradient at Point Caution, on San Juan Island, WA
(2011) Johnson, Jeff
Although they are integral to many marine ecosystems, relatively little is known about euendolithic (shell-boring) organisms outside the tropics. Here, I present a short survey of euendoliths inhabiting a site on the Pacific coast of North America. Shells were collected from sites in the intertidal and subtidal zone off Point Caution, on San Juan Island, WA. Casts of boreholes were photographed with a scanning electron microscope, and their morphology and diameter was matched to previously isolated cultures. Several types of green algae, as well as cyanobacteria and fungi, were found in the intertidal shells. The 11 meter deep subtidal site was dominated by the green alga Ostreobium, and the 23 meter site by the cyanobacteria Leptolyngbya. Only heavily eroded tracings were found at the 30 meter deep site.
Complex regulation and multiple developmental functions of misfire, the Drosophila melanogaster ferlin gene
(2007-03-26) Smith, Michelle K; Wakimoto, Barbara T.
Background: Ferlins are membrane proteins with multiple C2 domains and proposed functions in Ca2+ mediated membrane-membrane interactions in animals. Caenorhabditis elegans has two ferlin genes, one of which is required for sperm function. Mammals have several ferlin genes and mutations in the human dysferlin (DYSF) and otoferlin (OTOF) genes result in muscular dystrophy and hearing loss, respectively. Drosophila melanogaster has a single ferlin gene called misfire (mfr). A previous study showed that a mfr mutation caused male sterility because of defects in fertilization. Here we analyze the expression and structure of the mfr gene and the consequences of multiple mutations to better understand the developmental function of ferlins. Results: We show that mfr is expressed in the testis and ovaries of adult flies, has tissue-specific promoters, and expresses alternatively spliced transcripts that are predicted to encode distinct protein isoforms. Studies of 11 male sterile mutations indicate that a predicted Mfr testis isoform with five C2 domains and a transmembrane (TM) domain is required for sperm plasma membrane breakdown (PMBD) and completion of sperm activation during fertilization. We demonstrate that Mfr is not required for localization of Sneaky, another membrane protein necessary for PMBD. The mfr mutations vary in their effects in females, with a subset disrupting egg patterning and causing a maternal effect delay in early embryonic development. Locations of these mutations indicate that a short Mfr protein isoform carries out ferlin activities during oogenesis. Conclusion: The mfr gene exhibits complex transcriptional and post-transcriptional regulation and functions in three developmental processes: sperm activation, egg patterning, and early embryogenesis. These functions are in part due to the production of protein isoforms that vary in the number of C2 domains. These findings help establish D. melanogaster as model system for understanding ferlin function and dysfunction in animals, including humans.
Chloroplast genome sequencing analysis of Heterosigma akashiwo CCMP452 (West Atlantic) and NIES293 (West Pacific) strains
(2008) Cattolico, Rose Ann; Jacobs, Michael A.; Zhou, Yang; Chang, Jean; Duplessis, Melinda; Lybrand, Terry; McKay, John; Ong, Han Chuan; Sims, Elizabeth; Rocap, Gabrielle
Background: Heterokont algae form a monophyletic group within the stramenopile branch of the tree of life. These organisms display wide morphological diversity, ranging from minute unicells to massive, bladed forms. Surprisingly, chloroplast genome sequences are available only for diatoms, representing two (Coscinodiscophyceae and Bacillariophyceae) of approximately 18 classes of algae that comprise this taxonomic cluster. A universal challenge to chloroplast genome sequencing studies is the retrieval of highly purified DNA in quantities sufficient for analytical processing. To circumvent this problem, we have developed a simplified method for sequencing chloroplast genomes, using fosmids selected from a total cellular DNA library. The technique has been used to sequence chloroplast DNA of two Heterosigma akashiwo strains. This raphidophyte has served as a model system for studies of stramenopile chloroplast biogenesis and evolution. Results: H. akashiwo strain CCMP452 (West Atlantic) chloroplast DNA is 160,149 bp in size with a 21,822-bp inverted repeat, whereas NIES293 (West Pacific) chloroplast DNA is 159,370 bp in size and has an inverted repeat of 21,665 bp. The fosmid cloning technique reveals that both strains contain an isomeric chloroplast DNA population resulting from an inversion of their single copy domains. Both strains contain multiple small inverted and tandem repeats, non-randomly distributed within the genomes. Although both CCMP452 and NIES293 chloroplast DNAs contains 197 genes, multiple nucleotide polymorphisms are present in both coding and intergenic regions. Several protein-coding genes contain large, in-frame inserts relative to orthologous genes in other plastids. These inserts are maintained in mRNA products. Two genes of interest in H. akashiwo, not previously reported in any chloroplast genome, include tyrC, a tyrosine recombinase, which we hypothesize may be a result of a lateral gene transfer event, and an unidentified 456 amino acid protein, which we hypothesize serves as a G-protein-coupled receptor. The H. akashiwo chloroplast genomes share little synteny with other algal chloroplast genomes sequenced to date. Conclusion: The fosmid cloning technique eliminates chloroplast isolation, does not require chloroplast DNA purification, and reduces sequencing processing time. Application of this method has provided new insights into chloroplast genome architecture, gene content and evolution within the stramenopile cluster.
Effect of human leukocyte antigen heterozygosity on infectious disease outcome: The need for allele-specific measures
(2003) Lipstitch, Marc; Bergstrom, Carl T.; Antia, Rustom
Background: Doherty and Zinkernagel, who discovered that antigen presentation is restricted by the major histocompatibility complex (MHC, called HLA in humans), hypothesized that individuals heterozygous at particular MHC loci might be more resistant to particular infectious diseases than the corresponding homozygotes because heterozygotes could present a wider repertoire of antigens. The superiority of heterozygotes over either corresponding homozygote, which we term allele-specific overdominance, is of direct biological interest for understanding the mechanisms of immune response; it is also a leading explanation for the observation that MHC loci are extremely polymorphic and that these polymorphisms have been maintained through extremely long evolutionary periods. Recent studies have shown that in particular viral infections, heterozygosity at HLA loci was associated with a favorable disease outcome, and such findings have been interpreted as supporting the allele-specific overdominance hypothesis in humans. Methods: An algebraic model is used to define the expected population-wide findings of an epidemiologic study of HLA heterozygosity and disease outcome as a function of allele-specific effects and population genetic parameters of the study population. Results: We show that overrepresentation of HLA heterozygotes among individuals with favorable disease outcomes (which we term population heterozygote advantage) need not indicate allele-specific overdominance. On the contrary, partly due to a form of confounding by allele frequencies, population heterozygote advantage can occur under a very wide range of assumptions about the relationship between homozygote risk and heterozygote risk. In certain extreme cases, population heterozygote advantage can occur even when every heterozygote is at greater risk of being a case than either corresponding homozygote. Conclusion: To demonstrate allele-specific overdominance for specific infections in human populations, improved analytic tools and/or larger studies (or studies in populations with limited HLA diversity) are necessary.
On RNA interference as template immunity
(Indian Academy of Sciences, 2005) Bergstrom, Carl T.; Antia, Rustom
A population-epigenetic model to infer site-specific methylation rates from double-stranded DNA methylation patterns
(National Academy of Sciences USA, 2005) Genereux, Diane P.; Miner, Brooks E.; Bergstrom, Carl T.; Laird, Charles D.
Cytosine methylation is an epigenetic mechanism in eukaryotes that is often associated with stable transcriptional silencing, such as in X-chromosome inactivation and genomic imprinting. Aberrant methylation patterns occur in several inherited human diseases and in many cancers. To understand how methylated and unmethylated states of cytosine residues are transmitted during DNA replication, we develop a population-epigenetic model of DNA methylation dynamics. The model is informed by our observation that de novo methylation can occur on the daughter strand while leaving the opposing cytosine unmethylated, as revealed by the patterns of methylation on the two complementary strands of individual DNA molecules. Under our model, we can infer sitespecific rates of both maintenance and de novo methylation, values that determine the fidelity of methylation inheritance, from double-stranded methylation data. This approach can be used for populations of cells obtained from individuals without the need for cell culture. We use our method to infer cytosine methylation rates at several sites within the promoter of the human gene FMR1.
The disadvantage of combinatorial communication
(The Royal Society of London, 2004) Lachmann, Michael; Bergstrom, Carl T.
Combinatorial communication allows rapid and efficient transfer of detailed information, yet combinatorial communication is used by few, if any, non-human species. To complement recent studies illustrating the advantages of combinatorial communication, we highlight a critical disadvantage. We use the concept of information value to show that deception poses a greater and qualitatively different threat to combinatorial signalling than to non-combinatorial systems. This additional potential for deception may represent a strategic barrier that has prevented widespread evolution of combinatorial communication. Our approach has the additional benefit of drawing clear distinctions among several types of deception that can occur in communication systems.
Behavioral thermoregulation in lizards: importance of associated costs
(American Association for the Advancement of Science, 1974-05-31) Huey, Raymond B.
The Puerto Rican lizard Anolis cristatellus behaviorally regulates body temperature in an open habitat but passively tolerates lower and more variable temperatures in an adjacent forest where basking sites are few and distant. Thermoregulation may be adaptive only when costs resulting from associated losses of time and energy are low.
Plants versus animals: do they deal with stress in different ways?
(Society of Integrative and Comparative Biology, 2002) Huey, Raymond B.; Carlson, Margen; Crozier, Lisa; Frazier, Melanie; Hamilton, Hayden; Harley, Christopher; Hoang, Anhthu; Kingsolver, Joel G.
Both plants and animals respond to stress by using adaptations that help them evade, tolerate, or recover from stress. In a synthetic paper A. D. Bradshaw (1972) noted that basic biological differences between plants and animals will have diverse evolutionary consequences, including those influencing how they deal with stress. For instance, Bradshaw argued that animals, because they have relatively well-developed sensory and locomotor capacities, can often use behavior and movement to evade or ameliorate environmental stresses. In contrast, he predicted that plants will have to emphasize increased physiological tolerance or phenotypic plasticity, and also that plants should suffer stronger selection and show more marked differentiation along environmental gradients. Here we briefly review the importance of behavior in mitigating stress, the behavioral capacities of animals and plants, and examples of plant responses that are functionally similar to behaviors of animals. Next, we try to test some of Bradshaw’s predictions. Unfortunately, critical data often proved non-comparable: plant and animal biologists often study different stressors (e.g., water versus heat) and measure different traits (photosynthesis versus locomotion). Nevertheless, we were able to test some of Bradshaw’s predictions and some related ones of our own. As Bradshaw predicted, the phenology of plants is more responsive to climate shifts than is that of animals and the microdistributions of non-mobile, intertidal invertebrates (‘‘plant’’ equivalents) are more sensitive to temperature than are those of mobile invertebrates. However, mortality selection is actually weaker for plants than for animals. We hope that our review not only redraws attention to some fascinating issues Bradshaw raised, but also encourages additional tests of his predictions. Such tests should be informative.
Latitudinal pattern of between-altitude faunal similarity: mountains might be "higher" in the tropics
(The University of Chicago, 1978-01) Huey, Raymond B.
Moving up or down a mountain from a given site, one encounters faunas that differ by varying degrees. The elevational separation between sites obviously influences the magnitude of that difference (faunal similarity is inversely proportional to elevational separation); local environmental discontinuities, steepness of slope (Beals 1969), and certain global factors may also affect these “between-altitude” faunal similarities. Here I examine one possible global relationship, that of latitude and the extent of faunal similarity for reptilian and amphibian communities at different altitudes. I gathered these data to test Janzen’s (1967) hypothesis that mountains are effectively “higher” to animals in the tropics; if this is true, then “between-altitude” faunal similarity should vary directly with latitude.
How often do lizards "run on empty"?
(Ecological Society of America, 2001-01) Huey, Raymond B.; Pianka, Eric R.; Vitt, Laurie J.
Energy balance is relevant to diverse issues in ecology, physiology, and evolution. To determine whether lizards are generally in positive energy balance, we synthesized a massive data set on the proportion of individual lizards (N = 18223) with empty stomachs (127 species), representing nine families distributed on four continents, primarily in temperate zone deserts but also in the neotropics. The average percentage of individuals with empty stomachs is low (13.2%) across all species, even among desert lizards, suggesting that most lizards are in positive energy balance. Nevertheless, species vary substantially in this regard (among all species, 0% to 66% of individuals have empty stomachs). Several patterns are detectable among species with unusually high frequencies of empty stomachs. In particular, nocturnal lizards “run on empty” more often on average than do diurnal species (24.1% vs. 10.5%); and this pattern holds even for nocturnal vs. diurnal geckos (21.2% vs. 7.2%, respectively). Several (but not all) top predators have a higher frequency of empty stomachs than do species that feed at lower trophic levels. Diet breadth and body size appear unrelated to frequency of empty stomachs. Widely foraging species sometimes have a high frequency of empty stomachs relative to sit-and-wait species, but patterns vary among continents and appear to be confounded by phylogeny and trophic level. Ant-eating specialists have uniformly low frequencies of empty stomachs. Diurnal termite specialists also have low frequencies of empty stomachs, but nocturnal ones have high frequencies. Lizards from certain families (Gekkonidae [including Pygopodidae], Gymnophthlamidae, and Varanidae) are more likely to have empty stomachs than are those of other families (Agamidae, Iguanidae, Lacertidae, Scincidae, and Teiidae).
Supplemental oxygen and mountaineer death rates on Everest and K2
(American Medical Association, 2000-07-12) Huey, Raymond B.; Eguskitza, Xavier
The use of supplemental oxygen by Himalayan mountaineers has been debated for more than 8 decades. Although sometimes viewed as unsporting, supplemental-oxygen use may improve survival rates by increasing performance and lowering hypoxic stress. Analyses of death rates of mountaineers descending from high summits may reveal an impact of supplemental oxygen on survival because descending mountaineers are often near exhaustion and vulnerable to accident, storm, or illness during their descent.
Evaluating temperature regulation by field-active ectotherms: the fallacy of the inappropriate question
(University of Chicago, 1993-11) Hertz, Paul E.; Huey, Raymond B.; Stevenson, R. D.
We describe a research protocol for evaluating temperature regulation from data on small field-active ectothermic animals, especially lizards. The protocol requires data on body temperatures (Tb) of field-active ectotherms, on available operative temperatures (Te, “null temperatures” for nonregulating animals), and on the thermoregulatory set-point range (preferred body temperatures, Tset). These data are used to estimate several quantitative indexes that collectively summarize temperature regulation: the “precision” of body temperature (variance in Tb, or an equivalent metric), the “accuracy” of body temperature relative to the set-point range (the average difference between Tb and Tset), and the “effectiveness” of thermoregulation (the extent to which body temperatures are closer on the average to the set-point range than are operative temperatures). If additional data on the thermal dependence of performance are available, the impact of thermoregulation on performance (the extent to which performance is enhanced relative to that of nonregulating animals) can also be estimated. A sample analysis of the thermal biology of three Anolis lizards in Puerto Rico demonstrates the utility of the new protocol and its superiority to previous methods of evaluating temperature regulation. We also discuss several ways in which the research protocol can be extended and applied to other organisms.
Hot rocks and not-so-hot rocks: retreat-site selection by garter snakes and its thermal consequences
(Ecological Society of America, 1989-08) Huey, Raymond B.; Peterson, Charles R.; Arnold, Stevan J.; Porter, Warren P.
Studies of behavioral thermoregulation of ectotherms have typically focused only on active animals. However, most temperate-zone ectotherms actually spend more time sequestered in retreats (e.g., under rocks) than active above ground. We documented retreat-site selection during summer by gravid garter snakes (Thamnophis elegans) at Eagle Lake in northeastern California, USA. To explore the thermal consequences of retreat-site selection, we measured potential body temperatures in retreats and combined these with data on thermal tolerances, thermal preferences, and thermal dependence of metabolism and digestion. Garter snakes at Eagle Lake usually retreated under rocks of intermediate thickness (20-30 cm) even though both thinner and thicker rocks were available. Empirical and biophysical analyses of temperatures under rocks of various sizes and shapes demonstrated that rock thickness had the dominate effect on potential Tb available to snakes and in turn on thermal physiology. Snakes selecting thin rocks (<20 cm thick) or very shallow burrows would die of heat stress in midafternoon and would have strongly impaired physiological capacity from cold at night. Snakes selecting very thick rocks (>40 cm thick) or remaining at the bottom of deep burrows would not experience such extreme Tb, but neither would they warm to Tb in their preferred range. However, snakes selecting intermediate-thickness rocks would not overheat but would achieve preferred Tb for long periods – far longer than if they remained on the ground surface or moved up and down within a burrow. Interestingly, snakes selecting burrows or intermediate-thickness rocks may be able to have either the highest energy gain or the lowest overall metabolic rate, depending on the particular Tb they select. Medium-thickness rocks, the size normally selected by the snakes, offer them a variety of suitable thermoregulatory opportunites.
Ecological consequences of foraging mode
(Ecological Society of America, 1981-08) Huey, Raymond B.; Pianka, Eric R.
Desert lizards are typically either widely foraging or sit-and-wait predators, and these foraging modes are correlated with major differences in ecology. Foraging mode is related to the type of prey eaten by lizards. Widely foraging lizards in the Kalahari desert, the Western Australian desert, and the North American desert generally eat more prey that are sedentary, unpredictably distributed, and clumped (e.g., termites) or that are large and inaccessible (inactive scorpions) than do sit-and-wait lizards. In contrast, sit-and-wait lizards eat more prey that are active. Foraging mode also appears to influence the types of predators that in turn eat the lizards. For example, a sit-and-wait snake eats predominately widely foraging lizards. Crossovers in foraging mode thus exist between trophic levels. Widely foraging lizards may also encounter predators more frequently, as suggested by analyses of relative tail lengths; but tail break frequencies are ambiguous. Daily maintenance energetic expenditures of widely foraging lizards appear to be about 1.3-1.5 times greater than those of sit-and-wait lizards in the same habitats, but gross food gains are about 1.3-2.1 times greater. Widely foraging species also have lower relative clutch volumes, apparently in response to enhanced risks of predation. Foraging mode within one species varies with changes in food availability. Physiology, morphology, and risk of predation might generally restrict the flexibility of foraging mode. Because foraging mode constrains numerous important aspects of ecology, any general model of foraging velocity must be complex.
Behavioral Drive versus Behavioral Inertia in Evolution: A Null Model Approach
(University of Chicago Press, 2003-03) Huey, Raymond B.; Hertz, Paul E.; Sinervo, B.
Some biologists embrace the classical view that changes in behavior inevitably initiate or drive evolutionary changes in other traits, yet others note that behavior sometimes inhibits evolutionary changes. Here we develop a null model that quantifies the impact of regulatory behaviors (specifically, thermoregulatory behaviors) on body temperature and on performance of ectotherms. We apply the model to data on a lizard (Anolis cristatellus) and show that thermoregulatory behaviors likely inhibit selection for evolutionary shifts in thermal physiology with altitude. Because behavioral adjustments are commonly used by ectotherms to regulate physiological performance, regulatory behaviors should generally constrain rather than drive evolution, a phenomenon we call the “Bogert effect.” We briefly review a few other examples that contradict the classical view of behavior as the inevitable driving force in evolution. Overall, our analysis and brief review challenge the classical view that behavior is invariably the driving force in evolution, and instead our work supports the alternative view that behavior has diverse—and sometimes conflicting—effects on the directions and rates at which other traits evolve.
Temperature, Demography, and Ectotherm Fitness
(University of Chicago Press, 2001-08) Huey, Raymond B.; Berrigan, David
Multiple Mating, Sperm Competition, and Meiotic Drive
(Blackwell Publishing LTD, 1995) Haig, David; Bergstrom, Carl T.
Most discussions of "sperm competition" have ignored the potential for competition among the different sperm genotypes present in the ejaculate of a single male. Rivalry within ejaculates may limit cooperation among the members of an ejaculate when they compete with sperm produced by other males. A gene that gains an advantage in competition within an ejaculate (a segregation distorter) may increase in frequency even if it is associated with significant costs to organismal fitness. Therefore, selection will favor genes expressed in males that suppress competition within ejaculates. This may explain why sperm function is largely controlled by the diploid genotypes of the male progenitor, rather than by the genotypes of individual haploid sperm. Multiple mating by females will reduce the relative advantage of a segregation distorter whenever the distorter impairs the competitive effectiveness of the ejaculates in which it occurs. If the distorter is associated with costs to organismal fitness, selection will favor female mating behavior that reduces the distorter's equilibrium frequency. Competition within ejaculates may thus be one reason why females choose to mate with multiple males.
Separating equilibria in continuous signalling games
(The Royal Society of London, 2002-10-24) Bergstrom, Carl T.; Szamado, Szabolcs; Lachmann, Michael
Much of the theoretical literature on costly signalling concentrates on the separating equilibria of continuous signalling games. At such equilibria, every signaller sends a distinct signal, and signal receivers are able to exactly infer the signaller's condition from the signal sent. In this paper, we introduce a vector-field solution method which simplifies the process of solving for separating equilibria. Using this approach, we show that continuous signalling games can have low-cost separating equilibria despite conflicting interests between signaller and receiver. We find that contrary to prior arguments, honesty does not require wasteful signals. Finally, we examine signalling games in which different signallers have different minimal-cost signals, and provide a mathematical justification for the argument that even non-signalling traits will be exaggerated beyond their phenotypic optimum when they are used by other individuals to judge condition or quality.

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