vieSi34

Caenorhabditis elegans

[Psas-6::SAS-6reencoded-mA::GFP; Cbr-unc-119(+)]

Eric Miska et al. (2002) European Worm Meeting "Functional analysis of the micro RNA genes of C. elegans"

Ezequiel Alvarez-Saavedra, David P Bartel, Eric Miska, Nelson C Lau, Bob Horvitz, Victor Ambros, Allison Abbott

[European Worm Meeting, 2002]

* HHMI and Dept. Biology, MIT, Cambridge, MA 02139, USA Dept. Genetics, Dartmouth Medical School, Hanover, NH, 03755, USA # Whitehead Institute for Biomedical Research and Dept. Biology, MIT, Cambridge, MA 02142, USA

Thosapornvichai T et al. (2022) Environ Toxicol Pharmacol "Mitochondrial daysfunction from malathion and chlorpyrifos exposure is associated with degeneration of GABAergic neurons in Caenorhabditis elegans."

Jensen LT, Jensen AN, Huangteerakul C, Thosapornvichai T

[Environ Toxicol Pharmacol, 2022]

Toxicity resulting from off-target effects, beyond acetylcholine esterase inhibition, for the commonly used organophosphate (OP) insecticides chlorpyrifos (CPS) and malathion (MA) was investigated using Saccharomyces cerevisiae and Caenorhabditis elegans model systems. Mitochondrial damage and dysfunction were observed in yeast following exposure to CPS and MA, suggesting this organelle is a major target. In the C. elegans model, the mitochondrial unfolded protein response pathway showed the most robust induction from CPS and MA treatment among stress responses examined. GABAergic neurodegeneration was observed with CPS and MA exposure. Impaired movement observed in C. elegans exposed to CPS and MA may be the result of motor neuron damage. Our analysis suggests that stress from CPS and MA results in mitochondrial dysfunction, with GABAergic neurons sensitized to these effects. These findings may aid in the understanding of toxicity from CPS and MA from high concentration exposure leading to insecticide poisoning.

Wernick RI et al. (2016) Front Genet "Paths of Heritable Mitochondrial DNA Mutation and Heteroplasmy in Reference and gas-1 Strains of Caenorhabditis elegans."

Estes S, Howe DK, Wernick RI, Denver DR

[Front Genet, 2016]

Heteroplasmy-the presence of more than one mitochondrial DNA (mtDNA) sequence type in a cell, tissue, or individual-impacts human mitochondrial disease and numerous aging-related syndromes. Understanding the trans-generational dynamics of mtDNA is critical to understanding the underlying mechanisms of mitochondrial disease and evolution. We investigated mtDNA mutation and heteroplasmy using a set of wild-type (N2 strain) and mitochondrial electron transport chain (ETC) mutant (gas-1) mutant Caenorhabditis elegans mutation-accumulation (MA) lines. The N2 MA lines, derived from a previous experiment, were bottlenecked for 250 generations. The gas-1 MA lines were created for this study, and bottlenecked in the laboratory for up to 50 generations. We applied Illumina-MiSeq DNA sequencing to L1 larvae from five gas-1 MA lines and five N2 MA lines to detect and characterize mtDNA mutation and heteroplasmic inheritance patterns evolving under extreme drift. mtDNA copy number increased in both sets of MA lines: three-fold on average among the gas-1 MA lines and five-fold on average among N2 MA lines. Eight heteroplasmic single base substitution polymorphisms were detected in the gas-1 MA lines; only one was observed in the N2 MA lines. Heteroplasmy frequencies ranged broadly in the gas-1 MA lines, from as low as 2.3% to complete fixation (homoplasmy). An initially low-frequency (<5%) heteroplasmy discovered in the gas-1 progenitor was observed to fix in one gas-1 MA line, achieve higher frequency (37.4%) in another, and be lost in the other three lines. A similar low-frequency heteroplasmy was detected in the N2 progenitor, but was lost in all five N2 MA lines. We identified three insertion-deletion (indel) heteroplasmies in gas-1 MA lines and six indel variants in the N2 MA lines, most occurring at homopolymeric nucleotide runs. The observed bias toward accumulation of single nucleotide polymorphisms in gas-1 MA lines is consistent with the idea that impaired mitochondrial activity renders mtDNA more vulnerable to this type of mutation. The consistent increases in mtDNA copy number implies that extreme genetic drift provides a permissive environment for elevated organelle genome copy number in C. elegans reference and gas-1 strains. This study broadens our understanding of the heteroplasmic mitochondrial mutation process in a multicellular model organism.

LP256

Caenorhabditis elegans

Shaham S et al. (1992) Worm Breeder's Gazette "Molecular Analysis of the Cell Death Gene ced-3"

Horvitz HR, Shaham S

[Worm Breeder's Gazette, 1992]

MOLECULAR ANALYSIS OF THE CELL DEATH GENE ced-3 Shai Shaham and Bob Horvitz ~lMI, Dept. Biology, MIT, Cambridge, MA 02139

Beitel GJ et al. (1994) Worm Breeder's Gazette "An ACEDB For the Macintosh User Group"

Beitel GJ, Horvitz HR

[Worm Breeder's Gazette, 1994]

An ACEDB for the Macintosh User Group Greg Beitel (BEITEL@MIT.EDU) and H. R. Horvitz, DepL Biology, MIT, Cambndge, MA 02139, USA

Jin YS et al. (1994) Worm Breeder's Gazette "unc-25 Encodes a C. elegans Glutamic Acid Decarboxylase (GAD)"

Horvitz HR, Jin YS

[Worm Breeder's Gazette, 1994]

unc-25 encodes a C elegans glutamic acid decarboxylase (GAD) Yishi Jin and Bob Horvitz, HHMI, Dept. Biology, Mrr, Cambridge, MA 02139, USA

Saxena, Ayush Shekhar et al. (2019) International Worm Meeting "Evolution of the rate of copy-number and structural variant mutations under relaxed selection in Caenorhabditis elegans."

Saxena, Ayush Shekhar, Salomon, Matthew, Matsuba, Chikako, Baer, Charles, Rajaei, Moein

[International Worm Meeting, 2019]

Mutation Accumulation (MA) experiments have been a workhorse of evolutionary genetics for over fifty years, and much of what is known about the mutational process at both the phenotypic and molecular level has been learned from MA experiments. The advent of economical whole-genome short-read sequencing greatly increased our ability to characterize the rate and spectrum of base-substitution and short indel mutations. Copy-number variants (CNVs) and structural variants (SVs, e.g., inversions, translocations) have been more difficult to characterize. The paucity of information on the mutational properties of CNVs and SVs is significant because there is compelling evidence that those types of mutations underlie much variation in complex traits. We previously demonstrated by means of a "second-order MA" experiment (i.e., sets of MA lines founded from individual MA lines) with the nematode Caenorhabditis elegans that the rate of base-substitution and (especially) small indel mutations increased over the course of ~250 generations of minimal selection. Preliminary analyses of CNVs based on short-read Illumina sequence data suggested that a similar trend holds for CNVs, but the quantitative estimates of CNV mutation varied by over an order of magnitude depending on the input parameters of the analytical algorithm. To attempt to get a better handle on the CNV and SV mutation rates, we sequenced a small number of MA lines (N=5) with Pacific Biosciences long-read sequencing and used the resulting estimates to attempt to inform the analysis of our more copious short-read data (N>100) MA lines. Preliminary results suggest a conservative long CNV rate of approximately 5% that of small mutations (base subs + short indels). The data are biased toward deletions, but comparisons of the sequence of the ancestor of our MA lines with the C. elegans reference genome indicates that our analytical method has the capacity to detect insertions and inversions as well as deletions. We additionally report comparative MA data from an additional set of 25 C. elegans MA lines derived from a different starting genotype (PB306).

ZM6539

Caenorhabditis elegans