Networks of Causal Linkage Between Eigenmodes Characterize Behavioral Dynamics of Caenorhabditis elegans

Behavioral phenotyping of model organisms has played an important role in unravelling the complexities of animal behavior. Techniques for classifying behavior often rely on easily identified changes in posture and motion. However, such approaches are likely to miss complex behaviors that cannot be readily distinguished by eye (e.g., behaviors produced by high dimensional dynamics). To explore this issue, we focus on the model organism Caenorhabditis elegans, where behaviors have been extensively recorded and classified. Using a dynamical systems lens, we identify high dimensional, nonlinear causal relationships between four basic shapes that describe worm motion (eigenmodes, also called “eigenworms”). We find relationships between all pairs of eigenmodes, but the timescales of the interactions vary between pairs and across individuals. Using these varying timescales, we create “interaction profiles” to represent an individual’s behavioral dynamics. As desired, these profiles are able to distinguish well-known behavioral states: i.e., the profiles for foraging individuals are distinct from those of individuals exhibiting an escape response. More importantly, we find that interaction profiles can distinguish high dimensional behaviors among divergent mutant strains that were previously classified as phenotypically similar. Specifically, we find it is able to detect phenotypic behavioral differences not previously identified in strains related to dysfunction of hermaphrodite-specific neurons.

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Chlamydomonas IFT70/CrDYF-1 Is a Core Component of IFT Particle Complex B and Is Required for Flagellar Assembly

Molecular Biology of the Cell ◽

10.1091/mbc.e10-03-0191 ◽

2010 ◽

Vol 21 (15) ◽

pp. 2696-2706 ◽

Cited By ~ 44

Author(s):

Zhen-Chuan Fan ◽

Robert H. Behal ◽

Stefan Geimer ◽

Zhaohui Wang ◽

Shana M. Williamson ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Chlamydomonas Reinhardtii ◽

Posttranslational Modification ◽

Model Organism ◽

Intraflagellar Transport ◽

Apparent Size ◽

Model Organisms ◽

Core Component ◽

B Subunit ◽

Flagellar Assembly

DYF-1 is a highly conserved protein essential for ciliogenesis in several model organisms. In Caenorhabditis elegans, DYF-1 serves as an essential activator for an anterograde motor OSM-3 of intraflagellar transport (IFT), the ciliogenesis-required motility that mediates the transport of flagellar precursors and removal of turnover products. In zebrafish and Tetrahymena DYF-1 influences the cilia tubulin posttranslational modification and may have more ubiquitous function in ciliogenesis than OSM-3. Here we address how DYF-1 biochemically interacts with the IFT machinery by using the model organism Chlamydomonas reinhardtii, in which the anterograde IFT does not depend on OSM-3. Our results show that this protein is a stoichiometric component of the IFT particle complex B and interacts directly with complex B subunit IFT46. In concurrence with the established IFT protein nomenclature, DYF-1 is also named IFT70 after the apparent size of the protein. IFT70/CrDYF-1 is essential for the function of IFT in building the flagellum because the flagella of IFT70/CrDYF-1–depleted cells were greatly shortened. Together, these results demonstrate that IFT70/CrDYF-1 is a canonical subunit of IFT particle complex B and strongly support the hypothesis that the IFT machinery has species- and tissue-specific variations with functional ramifications.

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Review of Biological Effects of Acute and Chronic Radiation Exposure on Caenorhabditis elegans

Cells ◽

10.3390/cells10081966 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1966

Author(s):

Rabin Dhakal ◽

Mohammad Yosofvand ◽

Mahsa Yavari ◽

Ramzi Abdulrahman ◽

Ryan Schurr ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Ionizing Radiation ◽

Biological Effects ◽

Model Organism ◽

Model Organisms ◽

C Elegans ◽

Chronic Radiation ◽

Biological Responses ◽

Chronic Radiation Exposure ◽

Acute And Chronic Exposure

Knowledge regarding complex radiation responses in biological systems can be enhanced using genetically amenable model organisms. In this manuscript, we reviewed the use of the nematode, Caenorhabditis elegans (C. elegans), as a model organism to investigate radiation’s biological effects. Diverse types of experiments were conducted on C. elegans, using acute and chronic exposure to different ionizing radiation types, and to assess various biological responses. These responses differed based on the type and dose of radiation and the chemical substances in which the worms were grown or maintained. A few studies compared responses to various radiation types and doses as well as other environmental exposures. Therefore, this paper focused on the effect of irradiation on C. elegans, based on the intensity of the radiation dose and the length of exposure and ways to decrease the effects of ionizing radiation. Moreover, we discussed several studies showing that dietary components such as vitamin A, polyunsaturated fatty acids, and polyphenol-rich food source may promote the resistance of C. elegans to ionizing radiation and increase their life span after irradiation.

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PhenoMIP: High-Throughput Phenotyping of Diverse Caenorhabditis elegans Populations via Molecular Inversion Probes

G3 Genes|Genome|Genetics ◽

10.1534/g3.120.401656 ◽

2020 ◽

Vol 10 (11) ◽

pp. 3977-3990

Author(s):

Calvin Mok ◽

Gabriella Belmarez ◽

Mark L. Edgley ◽

Donald G. Moerman ◽

Robert H. Waterston

Keyword(s):

Caenorhabditis Elegans ◽

High Throughput ◽

Massively Parallel Sequencing ◽

Food Sources ◽

Relative Fitness ◽

Model Organisms ◽

Single Nucleotide Variants ◽

High Throughput Analysis ◽

Link Type ◽

Mutant Strains

Whether generated within a lab setting or isolated from the wild, variant alleles continue to be an important resource for decoding gene function in model organisms such as Caenorhabditis elegans. With advances in massively parallel sequencing, multiple whole-genome sequenced (WGS) strain collections are now available to the research community. The Million Mutation Project (MMP) for instance, analyzed 2007 N2-derived, mutagenized strains. Individually, each strain averages ∼400 single nucleotide variants amounting to ∼80 protein-coding variants. The effects of these variants, however, remain largely uncharacterized and querying the breadth of these strains for phenotypic changes requires a method amenable to rapid and sensitive high-throughput analysis. Here we present a pooled competitive fitness approach to quantitatively phenotype subpopulations of sequenced collections via molecular inversion probes (PhenoMIP). We phenotyped the relative fitness of 217 mutant strains on multiple food sources and classified these into five categories. We also demonstrate on a subset of these strains, that their fitness defects can be genetically mapped. Overall, our results suggest that approximately 80% of MMP mutant strains may have a decreased fitness relative to the lab reference, N2. The costs of generating this form of analysis through WGS methods would be prohibitive while PhenoMIP analysis in this manner is accomplished at less than one-tenth of projected WGS costs. We propose methods for applying PhenoMIP to a broad range of population selection experiments in a cost-efficient manner that would be useful to the community at large.

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Peel-1 negative selection promotes screening-free CRISPR-Cas9 genome editing in Caenorhabditis elegans

10.1101/2020.05.22.110353 ◽

2020 ◽

Cited By ~ 1

Author(s):

Troy A. McDiarmid ◽

Vinci Au ◽

Donald G. Moerman ◽

Catharine H. Rankin

Keyword(s):

Caenorhabditis Elegans ◽

Machine Vision ◽

Negative Selection ◽

Large Scale ◽

Genome Engineering ◽

Model Organism ◽

Model Organisms ◽

Behavioral Phenotypes ◽

Functional Studies ◽

Marker Selection

AbstractImproved genome engineering methods that enable automation of large and precise edits are essential for systematic investigations of genome function. We adapted peel-1 negative selection to an optimized Dual-Marker Selection (DMS) cassette protocol for CRISPR-Cas9 genome engineering in Caenorhabditis elegans and observed robust increases in multiple measures of efficiency that were consistent across injectors and four genomic loci. The use of Peel-1-DMS selection killed animals harboring transgenes as extrachromosomal arrays and spared genome edited integrants, often circumventing the need for visual screening to identify genome edited animals. To demonstrate the applicability of the approach, we created deletion alleles in the putative proteasomal subunit pbs-1 and the uncharacterized gene K04F10.3 and used machine vision to automatically characterize their phenotypic profiles, revealing homozygous essential and heterozygous behavioral phenotypes. These results provide a robust and scalable approach to rapidly generate and phenotype genome edited animals without the need for screening or scoring by eye.Author summaryThe ability to directly manipulate the genome and observe the resulting effects on the traits of an organism is a powerful approach to investigate gene function. CRISPR-based approaches to genome engineering have revolutionized such functional studies across model organisms but still face major challenges that limit the scope and complexity of projects that can be achieved in practice. Automating genome engineering and phenotyping would enable large-scale investigations of genome function in animals. Here, we describe the adaptation of peel-1 negative selection to an optimized dual-marker selection cassette CRISPR-Cas9 genome engineering method in C. elegans and combine it with automated machine vision phenotyping to achieve functional studies without the need for screening or scoring by eye. To demonstrate the applicability of the approach, we generated novel deletion alleles in two understudied genes, pbs-1 and K04F10.3, and used machine vision to characterize their phenotypic profiles, revealing homozygous lethal and heterozygous behavioral phenotypes. Our results open the door to systematic investigations of genome function in this model organism.

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The glycomes of Caenorhabditis elegans and other model organisms

Biochemical Society Symposium ◽

10.1042/bss0690117 ◽

2002 ◽

Vol 69 ◽

pp. 117-134 ◽

Cited By ~ 47

Author(s):

Stuart M. Haslam ◽

David Gems ◽

Howard R. Morris ◽

Anne Dell

Keyword(s):

Caenorhabditis Elegans ◽

Current Knowledge ◽

Structural Data ◽

Model Organisms ◽

Entire Genome ◽

C Elegans ◽

The Face ◽

Area Of Concern ◽

Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

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Geographic Variation in Behavior

10.1093/oso/9780195082951.001.0001 ◽

1999 ◽

Cited By ~ 8

Keyword(s):

Geographic Variation ◽

Animal Behavior ◽

Evolutionary Biology ◽

Behavioral Characteristics ◽

Behavioral Differences ◽

Methodological Issues ◽

Behavioral Evolution ◽

Evolutionary Patterns ◽

Wide Range

Studies of animal behavior often assume that all members of a species exhibit the same behavior. Geographic Variation in Behavior shows that, on the contrary, there is substantional variation within species across a wide range of taxa. Including work from pioneers in the field, this volume provides a balanced overview of research on behavioral characteristics that vary geographically. The authors explore the mechanisms by which behavioral differences evolve and examine related methodological issues. Taken together, the work collected here demonstrates that genetically based geographic variation may be far more widespread than previously suspected. The book also shows how variation in behavior can illuminate both behavioral evolution and general evolutionary patterns. Unique among books on behavior in its emphasis on geographic variation, this volume is a valuable new resource for students and researchers in animal behavior and evolutionary biology.

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In Search of Species-Specific SNPs in a Non-Model Animal (European Bison (Bison bonasus))—Comparison of De Novo and Reference-Based Integrated Pipeline of STACKS Using Genotyping-by-Sequencing (GBS) Data

Animals ◽

10.3390/ani11082226 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2226

Author(s):

Sazia Kunvar ◽

Sylwia Czarnomska ◽

Cino Pertoldi ◽

Małgorzata Tokarska

Keyword(s):

Reference Genome ◽

De Novo ◽

Bos Taurus ◽

Model Organism ◽

Genotyping By Sequencing ◽

Model Organisms ◽

European Bison ◽

Model Animal ◽

Pcr Duplicates ◽

Species Specific

The European bison is a non-model organism; thus, most of its genetic and genomic analyses have been performed using cattle-specific resources, such as BovineSNP50 BeadChip or Illumina Bovine 800 K HD Bead Chip. The problem with non-specific tools is the potential loss of evolutionary diversified information (ascertainment bias) and species-specific markers. Here, we have used a genotyping-by-sequencing (GBS) approach for genotyping 256 samples from the European bison population in Bialowieza Forest (Poland) and performed an analysis using two integrated pipelines of the STACKS software: one is de novo (without reference genome) and the other is a reference pipeline (with reference genome). Moreover, we used a reference pipeline with two different genomes, i.e., Bos taurus and European bison. Genotyping by sequencing (GBS) is a useful tool for SNP genotyping in non-model organisms due to its cost effectiveness. Our results support GBS with a reference pipeline without PCR duplicates as a powerful approach for studying the population structure and genotyping data of non-model organisms. We found more polymorphic markers in the reference pipeline in comparison to the de novo pipeline. The decreased number of SNPs from the de novo pipeline could be due to the extremely low level of heterozygosity in European bison. It has been confirmed that all the de novo/Bos taurus and Bos taurus reference pipeline obtained SNPs were unique and not included in 800 K BovineHD BeadChip.

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Effect of a Neuropeptide Gene on Behavioral States in Caenorhabditis elegans Egg-Laying

Genetics ◽

10.1093/genetics/154.3.1181 ◽

2000 ◽

Vol 154 (3) ◽

pp. 1181-1192 ◽

Cited By ~ 2

Author(s):

Laura E Waggoner ◽

Laura Anne Hardaker ◽

Steven Golik ◽

William R Schafer

Keyword(s):

Caenorhabditis Elegans ◽

Active Phase ◽

Egg Laying ◽

Sensory Cues ◽

Nematode Caenorhabditis Elegans ◽

Inactive State ◽

Recessive Mutations ◽

Inactive Phase ◽

Behavioral States ◽

Stimulation Of

Abstract Egg-laying behavior in the nematode Caenorhabditis elegans involves fluctuation between alternative behavioral states: an inactive state, during which eggs are retained in the uterus, and an active state, during which eggs are laid in bursts. We have found that the flp-1 gene, which encodes a group of structurally related neuropeptides, functions specifically to promote the switch from the inactive to the active egg-laying state. Recessive mutations in flp-1 caused a significant increase in the duration of the inactive phase, yet egg-laying within the active phase was normal. This pattern resembled that previously observed in mutants defective in the biosynthesis of serotonin, a neuromodulator implicated in induction of the active phase. Although flp-1 mutants were sensitive to stimulation of egg-laying by serotonin, the magnitude of their serotonin response was abnormally low. Thus, the flp-1-encoded peptides and serotonin function most likely function in concert to facilitate the onset of the active egg-laying phase. Interestingly, we observed that flp-1 is necessary for animals to down-regulate their rate of egg-laying in the absence of food. Because flp-1 is known to be expressed in interneurons that are postsynaptic to a variety of chemosensory cells, the FLP-1 peptides may function to regulate the activity of the egg-laying circuitry in response to sensory cues.

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Alliance of Genome Resources Portal: unified model organism research platform

Nucleic Acids Research ◽

10.1093/nar/gkz813 ◽

2019 ◽

Vol 48 (D1) ◽

pp. D650-D658 ◽

Cited By ~ 36

Author(s):

◽

Julie Agapite ◽

Laurent-Philippe Albou ◽

Suzi Aleksander ◽

Joanna Argasinska ◽

...

Keyword(s):

Gene Ontology ◽

Model Organism ◽

Model Organisms ◽

Data Types ◽

Primary Model ◽

Genomic Studies ◽

Health And Disease ◽

Extensive Body ◽

Access To Data ◽

Model Organism Databases

Abstract The Alliance of Genome Resources (Alliance) is a consortium of the major model organism databases and the Gene Ontology that is guided by the vision of facilitating exploration of related genes in human and well-studied model organisms by providing a highly integrated and comprehensive platform that enables researchers to leverage the extensive body of genetic and genomic studies in these organisms. Initiated in 2016, the Alliance is building a central portal (www.alliancegenome.org) for access to data for the primary model organisms along with gene ontology data and human data. All data types represented in the Alliance portal (e.g. genomic data and phenotype descriptions) have common data models and workflows for curation. All data are open and freely available via a variety of mechanisms. Long-term plans for the Alliance project include a focus on coverage of additional model organisms including those without dedicated curation communities, and the inclusion of new data types with a particular focus on providing data and tools for the non-model-organism researcher that support enhanced discovery about human health and disease. Here we review current progress and present immediate plans for this new bioinformatics resource.

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