Kleemann, Gunnar et al. (2011) International Worm Meeting "Delimiting a polymorphic longevity locus on the left arm of Chromosome IV using traditional and high throughput longevity assays."

Kruglyak, Leonid, Murphy, Coleen, Boom, Joshua, Kleemann, Gunnar

[International Worm Meeting, 2011]

A large body of work has been generated describing how aging is altered by changes in signaling pathways. Less well understood is how the known pathways differ across genetically polymorphic natural isolates of C. elegans. In order to explore how the longevity pathways have diverged in wild strains, we have assessed longevity across a panel of CB4856 x N2 recombinant inbred advanced intercross lines (RIAILs) (Rockman and Kruglyak 2009). We facilitated our analysis by developing a high-throughput longevity assay pipeline, "Chronos" to count worms and estimate longevity curves. While N2 and CB4856 longevity were similar, a number of the RIAIL life spans differed significantly from either parent suggesting that parental life span has converged, but hidden genetic variation is revealed when co-adapted alleles are separated. From the linkage data generated in the RIAIL based QTL (quantitative trait loci) analysis we identified a polymorphic region on the left arm of Chromosome IV that confers a longevity difference when the region is isolated on an isogenic N2 background. We have reduced the longevity-linked region from the initial 2.5 Mbp identified in the QTL analysis to <200 kb long region using Near Isogeneic Lines (NILs). The minimal region encompasses likely functional changes in only 8 genes. We are testing the candidate genes using both single gene and fosmid rescue. Additionally, In order to gain a deeper insight into the processes that differ between N2 and the short-lived NIL worms we are conducting a detailed phenotypic analysis of the NIL survival curves. To collect the large number of survival curves required to fully characterize the hazard (instantaneous likelihood of death) function shape, peak time and variation we are using an imaging robot in conjunction with the Chronos image analysis pipeline.

Hengartner MO (2001) Cell "Apoptosis: corralling the corpses."

Hengartner MO

[Cell, 2001]

One of the most impressive features of apoptosis is how quickly it all happens. One minute the cell is happily sitting there on its plastic lawn; the next-boom!-it is in convulsions, writhing in its death throes. Many a QuickTime movie has been produced to illustrate this point. Unfortunately, most of these movies stop shortly after the cell falls apart. While less photogenic, what happens to the remains of the cell after the camera stops rolling is no less impressive-at least in vivo.

Frezal L et al. (2015) Elife "C. elegans outside the Petri dish."

Frezal L, Felix MA

[Elife, 2015]

The roundworm Caenorhabditis elegans has risen to the status of a top model organism for biological research in the last fifty years. Among laboratory animals, this tiny nematode is one of the simplest and easiest organisms to handle. And its life outside the laboratory is beginning to be unveiled. Like other model organisms, C. elegans has a boom-and-bust lifestyle. It feasts on ephemeral bacterial blooms in decomposing fruits and stems. After resource depletion, its young larvae enter a migratory diapause stage, called the dauer. Organisms known to be associated with C. elegans include migration vectors (such as snails, slugs and isopods) and pathogens (such as microsporidia, fungi, bacteria and viruses). By deepening our understanding of the natural history of C. elegans, we establish a broader context and improved tools for studying its biology.

Archer, H. et al. (2017) International Worm Meeting "High throughput assessment of natural variation in the resistance to starvation stress in C. elegans using microfluidics."

Blue, B., Phillips, P.C., Banse, S., Archer, H.

[International Worm Meeting, 2017]

Caenorhabditis elegans typically feeds on rotting fruit and plant material in a fluctuating natural habitat, a boom-and-bust lifestyle. Moreover, stage specific developmental responses to low food concentration suggest that starvation-like conditions are a regular occurrence. In order to assess variation in the C. elegans starvation response under precisely controlled conditions and simultaneously phenotype a large number of individuals with high precision, we have developed a microfluidic device that, when combined with image scanning technology, allows for high-throughput assessment at a temporal resolution not previously feasible. Under these conditions worms exhibit a markedly reduced adult lifespan with strain-dependent variation in starvation resistance, ranging from <72 hours to ~120 hours. Initial results contrasting wildtype individuals with lipase mutants suggest a significant role for processes of fat metabolism in mediating resistance to starvation stress. Application of this device to a well-defined polymorphic population of C. elegans allows for mapping of the relationship between natural variation in genotypes and differences in starvation resistance.

Patel DS et al. (2019) Lab Anim (NY) "Digging deeper: methodologies for high-content phenotyping in Caenorhabditis elegans."

Xu N, Patel DS, Lu H

[Lab Anim (NY), 2019]

Deep phenotyping is an emerging conceptual paradigm and experimental approach aimed at measuring and linking many aspects of a phenotype to understand its underlying biology. To date, deep phenotyping has been applied mostly in cultured cells and used less in multicellular organisms. However, in the past decade, it has increasingly been recognized that deep phenotyping could lead to a better understanding of how genetics, environment and stochasticity affect the development, physiology and behavior of an organism. The nematode Caenorhabditis elegans is an invaluable model system for studying how genes affect a phenotypic trait, and new technologies have taken advantage of the worm's physical attributes to increase the throughput and informational content of experiments. Coupling of these technical advancements with computational and analytical tools has enabled a boom in deep-phenotyping studies of C. elegans. In this Review, we highlight how these new technologies and tools are digging into the biological origins of complex, multidimensional phenotypes.

S Le Comber et al. (1999) International C. elegans Meeting "Evolutionary & ecological aspects of aging in C. elegans"

L Partridge, S Le Comber, D Gems

[International C. elegans Meeting, 1999]

Traditionally, most work on aging in C. elegans has adopted the methods of classical genetics. Our aim is to extend this approach to include evolutionary biology, and in particular to address the question of the effect of life span extension on fitness. We are currently investigating this question in the laboratory, using a range of mutant types. Initially, we are measuring two components of fitness: the intrinsic rate of increase, r , which is frequently used as a global measure of fitness (1), and the ability of starved populations to survive over long periods. These give an indication of the effects of mutations on fitness in "boom" and "bust" conditions, respectively. Evolutionary optimality theory predicts the occurrence of trade-offs between different fitness traits including fecundity and life span (2). In C. elegans , reproduction by self-fertilization does not reduce life span (3), nor does increasing egg production (4), and mutation of daf-2 can extend life span without reducing brood size (5). This argues against a trade-off between fecundity and longevity in C. elegans . However, it is unclear whether the Age phenotype affects the length of the reproductive period and overall fecundity, where sperm number is not limiting. Furthermore, trade-offs between fecundity and longevity may not be detected under replete nutritional conditions. These issues are under investigation. One problem with laboratory analysis of fitness is that it is unclear how well laboratory measures of fitness correlate with the organism's fitness in the conditions to which it is adapted. Unfortunately, little is known about the ecology of C. elegans in the wild. For instance, the degree to which wild populations of C. elegans experience "boom and bust" cycles, or relatively stable populations, is unknown. Equally, the importance of males in wild populations, or whether they occur at all, is unknown. For this reason, we are also setting out to investigate the ecology of C. elegans in the wild. (1) Roff (1992) The Evolution of Life Histories; (2) Stearns (1992) The Evolution of Life Histories; (3) Friedman and Johnson (1988) Genetics 118: 75; (4) Gems and Riddle (1996) Nature 379: 723; (5) Gems et al. (1998) Genetics 150: 129.

Archer, Heather et al. (2019) International Worm Meeting "High throughput assessment of natural variation in the response to adult starvation in C. elegans using microfluidics."

Blue, Ben, Banse, Stephen, Archer, Heather, Phillips, Patrick

[International Worm Meeting, 2019]

Caenorhabditis elegans typically feeds on rotting fruit and plant material in a fluctuating natural habitat, a boom-and-bust lifestyle. Moreover, stage specific developmental responses to low food concentration suggest that starvation-like conditions are a regular occurrence. In order to assess variation in the C. elegans starvation response under precisely controlled conditions and simultaneously phenotype a large number of individuals with high precision, we have developed a microfluidic device that, when combined with image scanning technology, allows for high-throughput assessment at a temporal resolution not previously feasible and applied this to a large mapping panel of fully sequenced intercross lines. Under these conditions worms exhibit a markedly reduced adult lifespan with strain-dependent variation in starvation response, ranging from <72 hours to ~120 hours. We performed genome-wide mapping and epistatic analysis of the responses of 7,855 individuals spread across 72 mapping lines, identifying a number of different chromosomal regions responsible for this variation. Genetic differences for a subset of lines were confirmed using a multi-generational introgression analysis using backcrossing with selection. Overall, there is a clear genetic basis for natural variation in the response to food availability within this species.

Yang H et al. (2024) Proc Natl Acad Sci U S A "Glial expression of a steroidogenic enzyme underlies natural variation in hitchhiking behavior."

Cook DE, Kim H, Lee D, Lee J, Andersen EC, Yang H, Paik YK

[Proc Natl Acad Sci U S A, 2024]

Phoresy is an interspecies interaction that facilitates spatial dispersal by attaching to a more mobile species. Hitchhiking species have evolved specific traits for physical contact and successful phoresy, but the regulatory mechanisms involved in such traits and their evolution are largely unexplored. The nematode <i>Caenorhabditis elegans</i> displays a hitchhiking behavior known as nictation during its stress-induced developmental stage. Dauer-specific nictation behavior has an important role in natural <i>C. elegans</i> populations, which experience boom-and-bust population dynamics. In this study, we investigated the nictation behavior of 137 wild <i>C. elegans</i> strains sampled throughout the world. We identified species-wide natural variation in nictation and performed a genome-wide association mapping. We show that the variants in the promoter of <i>nta-1</i>, encoding a putative steroidogenic enzyme, underlie differences in nictation. This difference is due to the changes in <i>nta-1</i> expression in glial cells, which implies that glial steroid metabolism regulates phoretic behavior. Population genetic analysis and geographic distribution patterns suggest that balancing selection maintained two <i>nta-1</i> haplotypes that existed in ancestral <i>C. elegans</i> populations. Our findings contribute to further understanding of the molecular mechanism of species interaction and the maintenance of genetic diversity within natural populations.

Lee D et al. (2019) Nat Ecol Evol "Selection and gene flow shape niche-associated variation in pheromone response."

Kammenga JE, Zdraljevic S, Lee D, Riksen JAG, Wang J, Schroeder FC, Sterken MG, Frezal L, Felix MA, Cook DE, Andersen EC, Braendle C, Hsu JC

[Nat Ecol Evol, 2019]

From quorum sensing in bacteria to pheromone signalling in social insects, chemical communication mediates interactions among individuals in local populations. In Caenorhabditis elegans, ascaroside pheromones can dictate local population density; high levels of pheromones inhibit the reproductive maturation of individuals. Little is known about how natural genetic diversity affects the pheromone responses of individuals from diverse habitats. Here, we show that a niche-associated variation in pheromone receptor genes contributes to natural differences in pheromone responses. We identified putative loss-of-function deletions that impair duplicated pheromone receptor genes (srg-36 and srg-37), which were previously shown to be lost in population-dense laboratory cultures. A common natural deletion in srg-37 arose recently from a single ancestral population that spread throughout the world; this deletion underlies reduced pheromone sensitivity across the global C. elegans population. We found that many local populations harbour individuals with a wild-type or a deletion allele of srg-37, suggesting that balancing selection has maintained the recent variation in this pheromone receptor gene. The two srg-37 genotypes are associated with niche diversity underlying boom-and-bust population dynamics. We hypothesize that human activities likely contributed to the gene flow and balancing selection of srg-37 variation through facilitating the migration of species and providing a favourable niche for the recently arisen srg-37 deletion.

Lindblom TH et al. (2006) J Exp Zool A Comp Exp Biol "Xenobiotic detoxification in the nematode Caenorhabditis elegans."

Lindblom TH, Dodd AK

[J Exp Zool A Comp Exp Biol, 2006]

The nematode Caenorhabditis elegans is an important model organism for the study of such diverse aspects of animal physiology and behavior as embryonic development, chemoreception, and the genetic control of lifespan. Yet, even though the entire genome sequence of this organism was deposited into public databases several years ago, little is known about xenobiotic metabolism in C. elegans. In part, the paucity of detoxification information may be due to the plush life enjoyed by nematodes raised in the laboratory. In the wild, however, these animals experience a much greater array of chemical assaults. Living in the interstitial water of the soil, populations of C. elegans exhibit a boom and bust lifestyle characterized by prodigious predation of soil microbes punctuated by periods of dispersal as a non-developing alternative larval stage. During the booming periods of population expansion, these animals almost indiscriminately consume everything in their environment including any number of compounds from other animals, microorganisms, plants, and xenobiotics. Several recent studies have identified many genes encoding sensors and enzymes these nematodes may use in their xeno-coping strategies. Here, we will discuss these recent advances, as well as the efforts by our lab and others to utilize the genomic resources of the C. elegans system to elucidate this nematode''s molecular defenses against toxins. J. Exp. Zool. 305A:720-730, 2006. (c) 2006 Wiley-Liss, Inc.