564 results on '"genetic interactions"'
Search Results
552. Epistatic interactions determine the mutational pathways and coexistence of lineages in clonal Escherichia coli populations.
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Maharjan RP and Ferenci T
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- Escherichia coli Proteins genetics, Genetic Fitness, Epistasis, Genetic, Escherichia coli genetics, Evolution, Molecular, Mutation
- Abstract
Understanding how diversity emerges in a single niche is not fully understood. Rugged fitness landscapes and epistasis between beneficial mutations could explain coexistence among emerging lineages. To provide an experimental test of this notion, we investigated epistasis among four pleiotropic mutations in rpoS, mglD, malT, and hfq present in two coexisting lineages that repeatedly fixed in experimental populations of Escherichia coli. The mutations were transferred into the ancestral background individually or in combination of double or triple alleles. The combined competitive fitness of two or three beneficial mutations from the same lineage was consistently lower than the sum of the competitive fitness of single mutants--a clear indication of negative epistasis within lineages. We also found sign epistasis (i.e., the combined fitness of two beneficial mutations lower than the ancestor), not only from two different lineages (i.e., hfq and rpoS) but also from the same lineage (i.e., mglD and malT). The sign epistasis between loci of different lineages indeed indicated a rugged fitness landscape, providing an epistatic explanation for the coexistence of distinct rpoS and hfq lineages in evolving populations. The negative and sign epistasis between beneficial mutations within the same lineage can further explain the order of mutation acquisition., (© 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.)
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- 2013
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553. Enteric nervous system development: migration, differentiation, and disease.
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Lake JI and Heuckeroth RO
- Subjects
- Animals, Body Patterning physiology, Enteric Nervous System physiology, Gastrointestinal Tract embryology, Gastrointestinal Tract growth & development, Gene Expression Regulation, Developmental, Hirschsprung Disease genetics, Hirschsprung Disease prevention & control, Humans, Neural Crest cytology, Enteric Nervous System embryology, Enteric Nervous System growth & development, Gastrointestinal Tract innervation
- Abstract
The enteric nervous system (ENS) provides the intrinsic innervation of the bowel and is the most neurochemically diverse branch of the peripheral nervous system, consisting of two layers of ganglia and fibers encircling the gastrointestinal tract. The ENS is vital for life and is capable of autonomous regulation of motility and secretion. Developmental studies in model organisms and genetic studies of the most common congenital disease of the ENS, Hirschsprung disease, have provided a detailed understanding of ENS development. The ENS originates in the neural crest, mostly from the vagal levels of the neuraxis, which invades, proliferates, and migrates within the intestinal wall until the entire bowel is colonized with enteric neural crest-derived cells (ENCDCs). After initial migration, the ENS develops further by responding to guidance factors and morphogens that pattern the bowel concentrically, differentiating into glia and neuronal subtypes and wiring together to form a functional nervous system. Molecules controlling this process, including glial cell line-derived neurotrophic factor and its receptor RET, endothelin (ET)-3 and its receptor endothelin receptor type B, and transcription factors such as SOX10 and PHOX2B, are required for ENS development in humans. Important areas of active investigation include mechanisms that guide ENCDC migration, the role and signals downstream of endothelin receptor type B, and control of differentiation, neurochemical coding, and axonal targeting. Recent work also focuses on disease treatment by exploring the natural role of ENS stem cells and investigating potential therapeutic uses. Disease prevention may also be possible by modifying the fetal microenvironment to reduce the penetrance of Hirschsprung disease-causing mutations.
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- 2013
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554. All or nothing: protein complexes flip essentiality between distantly related eukaryotes.
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Ryan CJ, Krogan NJ, Cunningham P, and Cagney G
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- Gene Ontology, Genes, Essential, Genes, Fungal, Protein Interaction Mapping, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins metabolism, Schizosaccharomyces metabolism, Schizosaccharomyces pombe Proteins metabolism, Protein Interaction Maps, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics, Schizosaccharomyces genetics, Schizosaccharomyces pombe Proteins genetics
- Abstract
In the budding yeast Saccharomyces cerevisiae, the subunits of any given protein complex are either mostly essential or mostly nonessential, suggesting that essentiality is a property of molecular machines rather than individual components. There are exceptions to this rule, however, that is, nonessential genes in largely essential complexes and essential genes in largely nonessential complexes. Here, we provide explanations for these exceptions, showing that redundancy within complexes, as revealed by genetic interactions, can explain many of the former cases, whereas "moonlighting," as revealed by membership of multiple complexes, can explain the latter. Surprisingly, we find that redundancy within complexes cannot usually be explained by gene duplication, suggesting alternate buffering mechanisms. In the distantly related Schizosaccharomyces pombe, we observe the same phenomenon of modular essentiality, suggesting that it may be a general feature of eukaryotes. Furthermore, we show that complexes flip essentiality in a cohesive fashion between the two species, that is, they tend to change from mostly essential to mostly nonessential, or vice versa, but not to mixed patterns. We show that these flips in essentiality can be explained by differing lifestyles of the two yeasts. Collectively, our results support a previously proposed model where proteins are essential because of their involvement in essential functional modules rather than because of specific topological features such as degree or centrality.
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- 2013
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555. Systematic Triple-Mutant Analysis Uncovers Functional Connectivity between Pathways Involved in Chromosome Regulation
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Richard Alexander, Qiuqin Wu, Michael Shales, Tineke L. Lenstra, Frank C. P. Holstege, Nevan J. Krogan, Colm J. Ryan, Hannes Braberg, Julian Haase, James E. Haber, Kathleen Franks-Skiba, Tasha L. Johnson, Zach Lipkin-Moore, Jeffrey R. Johnson, and Kerry Bloom
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DNA Replication ,Saccharomyces cerevisiae Proteins ,Medical Physiology ,Mutant ,Saccharomyces cerevisiae ,Synthetic lethality ,Computational biology ,Biology ,Triple-mutant analysis ,Article ,Chromosomes ,General Biochemistry, Genetics and Molecular Biology ,Chromosome segregation ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,Gene ,lcsh:QH301-705.5 ,030304 developmental biology ,Cyclin ,0303 health sciences ,Human Genome ,Genetic interactions ,DNA replication ,Chromosome ,Rdh54 ,Chromatin ,lcsh:Biology (General) ,Generic health relevance ,Biochemistry and Cell Biology ,030217 neurology & neurosurgery ,Biotechnology ,DNA Damage - Abstract
Genetic interactions reveal the functional relationships between pairs of genes. In this study, we describe a method for the systematic generation and quantitation of triple mutants, termed triple-mutant analysis (TMA). We have used this approach to interrogate partially redundant pairs of genes in S. cerevisiae, including ASF1 and CAC1, two histone chaperones. After subjecting asf1Δ cac1Δ to TMA, we found that the Swi/Snf Rdh54 protein compensates for the absence of Asf1 and Cac1. Rdh54 more strongly associates with the chromatin apparatus and the pericentromeric region in the double mutant. Moreover, Asf1 is responsible for the synthetic lethality observed in cac1Δ strains lacking the HIRA-like proteins. A similar TMA was carried out after deleting both CLB5 and CLB6, cyclins that regulate DNA replication, revealing a strong functional connection to chromosome segregation. This approach can reveal functional redundancies that cannot be uncovered through traditional double-mutant analyses. Move to CSI collection when live -OR 10/09/2013 TS 31.07.13 note: the characters in italics in the summary/abstract, do not appear in italics when pasted in here. TS
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556. Accounting for genetic interactions improves modeling of individual quantitative trait phenotypes in yeast
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Forsberg, Simon K G and Forsberg, Simon K G
- Abstract
Experiments in model organisms report abundant genetic interactions underlying biologically important traits, whereas quantitative genetics theory predicts, and data support, that most genetic variance in populations is additive. Here we describe networks of capacitating genetic interactions that contribute to quantitative trait variation in a large yeast intercross population. The additive variance explained by individual loci in a network is highly dependent on the allele frequencies of the interacting loci. Modeling of phenotypes for multi-locus genotype classes in the epistatic networks is often improved by accounting for the interactions. We discuss the implications of these results for attempts to dissect genetic architectures and to predict individual phenotypes and long-term responses to selection.
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557. Differential genetic interactions of yeast stress response MAPK pathways
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Martin, Humberto, Shales, Michael, Fernandez-Piñar, Pablo, Wei, Ping, Molina, Maria, Fiedler, Dorothea, Shokat, Kevan M., Beltrao, Pedro, Lim, Wendell, and Krogan, Nevan J.
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Genetic Interactions ,Cell Wall Integrity ,Osmotic Shock ,3. Good health ,Stress Response - Abstract
Genetic interaction screens have been applied with great success in several organisms to study gene function and the genetic architecture of the cell. However, most studies have been performed under optimal growth conditions even though many functional interactions are known to occur under specific cellular conditions. In this study, we have performed a large-scale genetic interaction analysis in Saccharomyces cerevisiae involving approximately 49 × 1,200 double mutants in the presence of five different stress conditions, including osmotic, oxidative and cell wall-altering stresses. This resulted in the generation of a differential E-MAP (or dE-MAP) comprising over 250,000 measurements of conditional interactions. We found an extensive number of conditional genetic interactions that recapitulate known stress-specific functional associations. Furthermore, we have also uncovered previously unrecognized roles involving the phosphatase regulator Bud14, the histone methylation complex COMPASS and membrane trafficking complexes in modulating the cell wall integrity pathway. Finally, the osmotic stress differential genetic interactions showed enrichment for genes coding for proteins with conditional changes in phosphorylation but not for genes with conditional changes in gene expression. This suggests that conditional genetic interactions are a powerful tool to dissect the functional importance of the different response mechanisms of the cell., Molecular Systems Biology, 11 (4), ISSN:1744-4292
558. Reproductive risk factors in breast cancer and genetic hormonal pathways: a gene-environment interaction in the MCC-Spain project
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Javier Llorca, José-Juan Jiménez-Moleón, Jéssica Alonso-Molero, Victor Moreno, Conchi Moreno-Iribas, Pilar Amiano, Adonina Tardón, Camilo Palazuelos-Calderón, Beatriz Pérez-Gómez, Gemma Castaño-Vinyals, Vicente Martín-Sánchez, Marina Pollán, Nuria Aragonés, Trinidad Dierssen-Sotos, Manolis Kogevinas, Antonio J. Molina, Jone M. Altzibar, Inés Gómez-Acebo, Marcela Guevara, Universidad de Cantabria, Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Fundación Marqués de Valdecilla, International Cancer Genome Consortium, Junta de Castilla y León (España), Regional Government of Andalusia (España), Generalitat Valenciana (España), Fundación La Caixa, Basque Government (España), Gobierno de la Región de Murcia (España), Unión Europea. Comisión Europea, Asociación Española Contra el Cáncer, Fundación Caja de Ahorros de Asturias, University of Oviedo (España), and Universitat de Barcelona
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0301 basic medicine ,Oncology ,Cancer Research ,Logistic regression ,Reproductive risk ,Breast cancer ,Pregnancy ,Risk Factors ,Surveys and Questionnaires ,Cyclic AMP Response Element-Binding Protein ,Reproduction ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Parity ,Basic-Leucine Zipper Transcription Factors ,src-Family Kinases ,Risk factors for breast cancer ,Female ,Reproductive Factors ,Metabolic Networks and Pathways ,Research Article ,Adult ,medicine.medical_specialty ,Breast Neoplasms ,Nerve Tissue Proteins ,Biology ,Human reproduction ,Polymorphism, Single Nucleotide ,Ribosomal Protein S6 Kinases, 90-kDa ,lcsh:RC254-282 ,Càncer de mama ,03 medical and health sciences ,Internal medicine ,Breast Cancer ,medicine ,Genetics ,Humans ,Factors sexuals en les malalties ,Genetic Predisposition to Disease ,Allele ,KEGG ,Reproducció humana ,Gene ,Reproductive factors ,Alleles ,Aged ,Mama -- Cáncer ,Genetic interactions ,medicine.disease ,Hormones ,Activating Transcription Factor 6 ,030104 developmental biology ,Genetic Interactions ,Spain ,Mutation ,Mama -- Càncer ,Sex factors in disease ,Genètica ,Hormone - Abstract
Samples: Biological samples were stored at the biobanks supported by Instituto de Salud Carlos III- FEDER: Parc de Salut MAR Biobank (MARBiobanc) (RD09/0076/00036), “Biobanco La Fe” (RD 09 0076/00021) and FISABIO Biobank (RD09 0076/00058), and also at the Public Health Laboratory from Gipuzkoa, the Basque Biobank, the ICOBIOBANC (sponsored by the Catalan Institute of Oncology), the IUOPA Biobank from the University of Oviedo and the ISCIII Biobank. Genotyping: SNP genotyping services were provided by the Spanish “Centro Nacional de Genotipado” (CEGEN-ISCIII)”., Background: Reproductive factors are well known risk factors for breast cancer; however, little is known about how genetic variants in hormonal pathways interact with that relationship. Methods: One thousand one hundred thirty nine cases of breast cancer in women and 1322 frequency-matched controls were compared. Genetic variants in hormonal pathways (identified in the Kyoto Encyclopedia of Genes and Genomes) were screened according to their relationship with breast cancer using the Cochran-Armitage statistic. Information on reproductive factors was obtained using a face-to-face questionnaire. The interaction among the selected genetic variants and reproductive factors was tested with logistic regression. Results: Concerning C allele in rs2229712, compared to nulliparity in non-carriers the ORs for 1–2 and > 2 deliveries were 0.48 (0.28–0.81) and 0.34 (0.19–0.59), and in C carriers they were 0.92 (0.42–1.98) and 0.71 (0.31–1.61). Similar results were found in women carrying the C allele in rs1269851. Carriers of Allele T in rs35652107 and allele C in rs6018027 had the delivery number effect more pronounced. Conclusions: The number of deliveries had a dose-response protective effect on breast cancer; women carrying C allele in rs2229712 did not benefit from this protective effect., This work was partially funded by the “Accion Transversal del Cancer”, approved by the Spanish Ministry Council on the 11th October 2007; The Instituto de Salud Carlos III-FEDER [PI08/1770, PI08/0533, PI08/1359, PI09/ 00773-Cantabria, PI09/01286-León, PI09/01903-Valencia, PI09/02078-Huelva, PI09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032]; The Fundación Marqués de Valdecilla [API 10/09]; The ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036)); The Junta de Castilla y León [LE22A10–2]; The Consejería de Salud of the Junta de Andalucía [2009-S0143]; The Conselleria de Sanitat of the Generalitat Valenciana [AP_061/10]; The Recercaixa [2010ACUP 00310]; The Regional Government of the Basque Country; The Consejería de Sanidad de la Región de Murcia; The European Commission [grants FOOD-CT-2006-036224-HIWATE]; The Spanish Association Against Cancer (AECC) Scientific Foundation; The Catalan Government DURSI [grant 2014SGR647]; The Fundación Caja de Ahorros de Asturias; and the University of Oviedo.
559. Plant genetic variation mediates an indirect ecological effect between belowground earthworms and aboveground aphids
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Singh, Akanksha, Braun, Julia, Decker, Emilia, Hans, Sarah, Wagner, Agnes, Weisser, Wolfgang W, and Zytynska, Sharon E
- Subjects
Aphis fabae ,Competitive Behavior ,Food Chain ,Population Dynamics ,fungi ,Acyrthosiphon pisum ,Genetic interactions ,Aboveground-belowground interactions ,Genetic Variation ,food and beverages ,Nitrogen Cycle ,biochemical phenomena, metabolism, and nutrition ,Vicia faba ,Plant genotype ,Environmental Science(all) ,Aphids ,Animals ,Biomass ,Oligochaeta ,Research Article - Abstract
Background Interactions between aboveground and belowground terrestrial communities are often mediated by plants, with soil organisms interacting via the roots and aboveground organisms via the shoots and leaves. Many studies now show that plant genetics can drive changes in the structure of both above and belowground communities; however, the role of plant genetic variation in mediating aboveground-belowground interactions is still unclear. We used an earthworm-plant-aphid model system with two aphid species (Aphis fabae and Acyrthosiphon pisum) to test the effect of host-plant (Vicia faba) genetic variation on the indirect interaction between the belowground earthworms (Eisenia veneta) on the aboveground aphid populations. Results Our data shows that host-plant variety mediated an indirect ecological effect of earthworms on generalist black bean aphids (A. fabae), with earthworms increasing aphid growth rate in three plant varieties but decreasing it in another variety. We found no effect of earthworms on the second aphid species, the pea aphid (A. pisum), and no effect of competition between the aphid species. Plant biomass was increased when earthworms were present, and decreased when A. pisum was feeding on the plant (mediated by plant variety). Although A. fabae aphids were influenced by the plants and worms, they did not, in turn, alter plant biomass. Conclusions Previous work has shown inconsistent effects of earthworms on aphids, but we suggest these differences could be explained by plant genetic variation and variation among aphid species. This study demonstrates that the outcome of belowground-aboveground interactions can be mediated by genetic variation in the host-plant, but depends on the identity of the species involved.
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560. CAP protein superfamily members in Toxocara canis
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Neil D. Young, Andreas Hofmann, Ross S. Hall, Robin B. Gasser, Andreas J. Stroehlein, Abdul Jabbar, Pasi K. Korhonen, and Paul W. Sternberg
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0301 basic medicine ,Transcription, Genetic ,Nematodes ,Helminth protein ,Transcriptome ,03 medical and health sciences ,Animals ,Amino Acid Sequence ,Gene ,Caenorhabditis elegans ,Pathogenesis-related protein ,Genetics ,biology ,Research ,Genetic interactions ,Toxocara canis ,Helminth Proteins ,CAP (SCP/TAPS) protein genes ,030108 mycology & parasitology ,biology.organism_classification ,3. Good health ,030104 developmental biology ,Canis ,Infectious Diseases ,Parasitology ,Immunology ,Transcription profiles - Abstract
Background Proteins of the cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 (CAP) superfamily are recognized or proposed to play roles in parasite development and reproduction, and in modulating host immune attack and infection processes. However, little is known about these proteins for most parasites. Results In the present study, we explored CAP proteins of Toxocara canis, a socioeconomically important zoonotic roundworm. To do this, we mined and curated transcriptomic and genomic data, predicted and curated full-length protein sequences (n = 28), conducted analyses of these data and studied the transcription of respective genes in different developmental stages of T. canis. In addition, based on information available for Caenorhabditis elegans, we inferred that selected genes (including lon-1, vap-1, vap-2, scl-1, scl-8 and scl-11 orthologs) of T. canis and their interaction partners likely play central roles in this parasite’s development and/or reproduction via TGF-beta and/or insulin-like signaling pathways, or via host interactions. Conclusion In conclusion, this study could provide a foundation to guide future studies of CAP proteins of T. canis and related parasites, and might assist in finding new interventions against diseases caused by these parasites. Electronic supplementary material The online version of this article (doi:10.1186/s13071-016-1642-y) contains supplementary material, which is available to authorized users.
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561. Network-dosage compensation topologies as recurrent network motifs in natural gene networks
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Ping Liu, Ruijie Song, and Murat Acar
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Systems biology ,Gene regulatory network ,Genomics ,Computational biology ,Saccharomyces cerevisiae ,Biology ,Network topology ,Network motifs ,Yeast galactose network ,Structural Biology ,Modelling and Simulation ,Gene duplication ,Gene Regulatory Networks ,Gene ,Molecular Biology ,Genetics ,Stochasticity ,Dosage compensation ,Applied Mathematics ,Fungal genetics ,Genetic interactions ,Computer Science Applications ,Network-dosage compensation ,Modeling and Simulation ,Proteolysis ,Genome, Fungal ,Research Article - Abstract
Background Global noise in gene expression and chromosome duplication during cell-cycle progression cause inevitable fluctuations in the effective number of copies of gene networks in cells. These indirect and direct alterations of network copy numbers have the potential to change the output or activity of a gene network. For networks whose specific activity levels are crucial for optimally maintaining cellular functions, cells need to implement mechanisms to robustly compensate the effects of network dosage fluctuations. Results Here, we determine the necessary conditions for generalized N-component gene networks to be network-dosage compensated and show that the compensation mechanism can robustly operate over large ranges of gene expression levels. Furthermore, we show that the conditions that are necessary for network-dosage compensation are also sufficient. Finally, using genome-wide protein-DNA and protein-protein interaction data, we search the yeast genome for the abundance of specific dosage-compensation motifs and show that a substantial percentage of the natural networks identified contain at least one dosage-compensation motif. Conclusions Our results strengthen the hypothesis that the special network topologies that are necessary for network-dosage compensation may be recurrent network motifs in eukaryotic genomes and therefore may be an important design principle in gene network assembly in cells.
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562. Propagation of Large Concentration Changes in Reversible Protein-Binding Networks
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Maslov, Sergei and Ispolatov, I.
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- 2007
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563. Complex Interactions with Females and Rival Males Limit the Evolution of Sperm Offence and Defence
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Bjork, Adam, Starmer, William T., Higginson, Dawn M., Rhodes, Christopher J., and Pitnick, Scott
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- 2007
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564. Phytochromes, Cryptochromes, Phototropin: Photoreceptor Interactions in Plants
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Casal, Jorge J.
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- 2000
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