age-1(hx546) is a recessive mutant allele in Caenorhabditis elegans that results in an increase in mean life span averaging 40% and in maximal life span averaging 60% at 20 degrees; at 25 degrees age-1(hx546) averages a 65% increase in mean life span (25.3 days vs. 15.0 days) and a 110% increase in maximum life span (46.2 days vs. 22.0 days for wild-type hermaphrodites). Mutant males also show extended life spans. age-1(hx546) is associated with a 75% decrease in hermaphrodite self-fertility as compared to the age-1+ allele at 20 degrees. Using two novel strategies for following the segregation of age-1, we present evidence that longer life results from a mutation in a single gene that increases the probability of survival at all chronological ages. The long-life and reduced-fertility phenotypes cosegregate and are tightly linked to fer-15, a locus on linkage group II. age-1(hx546) does not affect the timing of larval molts, the length of embryogenesis, food uptake, movement, or behavior in any way tested. Although age-1(hx546) lowers hermaphrodite self-fertility, it does not markedly affect the length of the reproductive period with all the increase in life expectancy due to an increase in the length of postreproductive life. In so far as we are aware, this mutant in age-1 is the only instance of a well-characterized genetic locus in which the mutant form results in lengthened fife. It is likely that the action of age-1 in lengthening life results not from eliminating a programmed aging function but rather from reduced hermaphrodite self-fertility or from some other unknown metabolic or physiologic alteration.

https://www.genetics.org/content/genetics/118/1/75.full.pdf

A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility.

Identification of genes required for cytoplasmic localization in early C. elegans embryos

Mutations in the Caenorhabditis elegans genes lin-14, lin-28, and lin-29 cause heterochronic developmental defects: the timing of specific developmental events in several tissues is altered relative to the timing of events in other tissues. These defects result from temporal transformations in the fates of specific cells, that is, certain cells express fates normally expressed by cells generated at other developmental stages. The identification and characterization of genes that can be mutated to cause heterochrony support the proposal that heterochrony is a mechanism for phylogenetic change and suggest cellular and genetic bases for heterochronic variation.

https://science.sciencemag.org/content/sci/226/4673/409.full.pdf

Heterochronic mutants of the nematode Caenorhabditis elegans

Most metazoans occur as two sexes. Surprisingly, molecular analyses have hitherto indicated that sex-determining mechanisms differ completely between phyla. Here we present evidence to the contrary. We have isolated the male sexual regulatory gene mab-3 from the nematode Caenorhabditis elegans and found that it is related to the Drosophila melanogaster sexual regulatory gene doublesex (dsx)2. Both genes encode proteins with a DNA-binding motif that we have named the 'DM domain'. Both genes control sex-specific neuroblast differentiation and yolk protein gene transcription; dsx controls other sexually dimorphic features as well. The form of DSX that is found in males can direct male-specific neuroblast differentiation in C. elegans. This structural and functional similarity between phyla suggests a common evolutionary origin of at least some aspects of sexual regulation. We have identified a human gene, DMT1, that encodes a protein with a DM domain and find that DMT1 is expressed only in testis. DMT1 maps to the distal short arm of chromosome 9, a location implicated in human XY sex reversal. Proteins with DM domains may therefore also regulate sexual development in mammals.

Evidence for evolutionary conservation of sex-determining genes

https://www.cell.com/cell/pdf/S0092-8674(01)00612-2.pdf

Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development

Six schemes were used to identify 80 independent recessive lethal deficiencies of linkage group (LG) II following X-ray treatment of the nematode Caenorhabditis elegans. Complementation tests between the deficiencies and ethyl methanesulfonate-induced recessive visible, lethal and sterile mutations and between different deficiencies were used to characterize the extents of the deficiencies. Deficiency endpoints thus helped to order 36 sites within a region representing about half of the loci on LG II and extending over about 5 map units. New mutations occurring in this region can be assigned to particular segments of the map by complementation tests against a small number of deficiencies; this facilitates the assignment of single-site mutations to particular genes, as we illustrate. Five sperm-defective and five oocyte-defective LG II sterile mutants were identified and mapped. Certain deficiency-by-deficiency complementation tests allowed us to suggest that the phenotypes of null mutations at two loci represented by visible alleles are wild type and that null mutations at a third locus confer a visible phenotype. A segment of LG II that is about 12 map units long and largely devoid of identified loci seems to be greatly favored for crossing over.

https://www.genetics.org/content/genetics/108/2/331.full.pdf

Caenorhabditis elegans deficiency mapping

The transmission of the yeast 2 μm DNA plasmid has been examined in heterokaryons formed between a haploid donor cell containing the plasmid and a haploid recipient cell lacking the plasmid. Strains lacking the plasmid were mated to donor strains and cytoductants, haploid exconjugants arising from heterokaryons, were selected. The cytoductants bearing the genotype of the recipient cells were then tested for the presence of 2 μm DNA. The frequency with which the recipient received plasmid copies varied between 0 and 46%. This frequency depended on the recipient strain but was not highly dependent on whether or not the donor strain carried a kar1 mutation. Exceptional cytoductants, which had acquired a chromosome from the mating partner, were examined and found to have a much greater probability of acquiring plasmid DNA than cytoductants in general. This correlation supports the contention that plasmid copies are associated with the nucleus. In one mating the donor strain contained nearly equal amounts of two physically distinct plasmid types. Of the cytoductants bearing the recipient genotype which had acquired the plasmid during mating, most contained only one of the two plasmid types present in the donor. Analysis of this result using a Poisson distribution indicates that the average number of plasmid copies transmitted between nuclei of a heterokaryon is 0.2.

D. Christine Sigurdson

Papers

Caenorhabditis elegans deficiency mapping

Characterization of the transmission during cytoductant formation of the 2 μm DNA plasmid from Saccharomyces