Natural selection is expected to eliminate genetic incompatibilities from interbreeding populations. We have identified a globally distributed incompatibility in the primarily selfing species Caenorhabditis elegans that has been maintained despite its negative consequences for fitness. Embryos homozygous for a naturally occurring deletion of the zygotically acting gene, zeel-1, arrest if their sperm parent carries an incompatible allele of a second, paternal effect locus, peel-1. The two interacting loci are tightly linked, with incompatible alleles occurring in linkage disequilibrium in two common haplotypes. These haplotypes exhibit elevated sequence divergence, and population genetic analyses of this region indicate that natural selection is preserving both haplotypes in the population. Our data suggest that long-term maintenance of a balanced polymorphism has permitted the incompatibility to persist despite gene flow across the rest of the genome.Caenorhabditis elegans is a globally distributed species of free-living, bacteria-eating nematode. Although rare males contribute at a low rate to outcrossing, C. elegans occurs primarily as inbred, self-fertilizing hermaphrodites (1-4). A wild isolate from Hawaii, CB4856, has been identified among well-studied isolates as the most divergent at the sequence level from the standard laboratory strain, N2, derived from an isolate from Bristol, England (5-7). As a result of this sequence divergence, the Hawaiian strain is widely used to map mutations induced in the Bristol background. Genetic incompatibility between Bristol and HawaiiWe generated recombinant inbred lines (RILs) from the tenth generation of an advanced intercross between Bristol and Hawaii to study natural genetic variation in C. elegans, and we genotyped the RILs at 1450 single nucleotide polymorphism markers (8). We noted that a region on the left arm of chromsome I exhibited a dramatic deficit of Hawaii alleles among the RILs. Of 239 RILs, only five carried the Hawaii allele at the most skewed marker, and simulations of the intercross pedigree indicated that this allele frequency skew could not have arisen by drift, suggesting that selection had acted during construction of the RILs (Fig. S1). We then crossed Hawaii to a Bristol strain carrying a visible marker located 10cM from the most skewed RIL marker, and we examined F2 progeny produced by self-fertilizing F1 hermaphrodites. Surprisingly, approximately 25% of F2 progeny arrested as embryos, and embryonic lethality segregated opposite the visible marker (Table 1). F2 lethality was not an effect of the marker: self-fertilizing F1 hermaphrodites derived from reciprocal crosses between Hawaii and wildtype Bristol produced 25% dead embryos, as did F1 hermaphrodites mated to F1 males (Fig. 1).

The budding yeast Saccharomyces cerevisiae has been used by humans for millennia to make wine, beer and bread. More recently, it became a key model organism for studies of eukaryotic biology and for genomic analysis. However, relatively little is known about the natural lifestyle and population genetics of yeast. One major question is whether genetically diverse yeast strains mate and recombine in the wild. We developed a method to infer the evolutionary history of a species from genome sequences of multiple individuals and applied it to whole-genome sequence data from three strains of Saccharomyces cerevisiae and the sister species Saccharomyces paradoxus. We observed a pattern of sequence variation among yeast strains in which ancestral recombination events lead to a mosaic of segments with shared genealogy. Based on sequence divergence and the inferred median size of shared segments (approximately 2,000 bp), we estimated that although any two strains have undergone approximately 16 million cell divisions since their last common ancestor, only 314 outcrossing events have occurred during this time (roughly one every 50,000 divisions). Local correlations in polymorphism rates indicate that linkage disequilibrium in yeast should extend over kilobases. Our results provide the initial foundation for population studies of association between genotype and phenotype in S. cerevisiae.

The genetic variants underlying complex traits are often elusive even in powerful model organisms such as Caenorhabditis elegans with controlled genetic backgrounds and environmental conditions. Two major contributing factors are: (1) the lack of statistical power from measuring the phenotypes of small numbers of individuals, and (2) the use of phenotyping platforms that do not scale to hundreds of individuals and are prone to noisy measurements. Here, we generated a new resource of 359 recombinant inbred strains that augments the existing C. elegans N2xCB4856 recombinant inbred advanced intercross line population. This new strain collection removes variation in the neuropeptide receptor gene npr-1, known to have large physiological and behavioral effects on C. elegans and mitigates the hybrid strain incompatibility caused by zeel-1 and peel-1, allowing for identification of quantitative trait loci that otherwise would have been masked by those effects. Additionally, we optimized highly scalable and accurate high-throughput assays of fecundity and body size using the COPAS BIOSORT large particle nematode sorter. Using these assays, we identified quantitative trait loci involved in fecundity and growth under normal growth conditions and after exposure to the herbicide paraquat, including independent genetic loci that regulate different stages of larval growth. Our results offer a powerful platform for the discovery of the genetic variants that control differences in responses to drugs, other aqueous compounds, bacterial foods, and pathogenic stresses.

A sperm-delivered toxin and an embryo-expressed antidote form a co-adapted gene complex in C. elegans that promotes its own transmission to the detriment of organisms carrying it.

Many animals alter their reproductive strategies in response to environmental stress. Here we have investigated how L4 hermaphrodites of Caenorhabditis elegans respond to starvation. To induce starvation, we removed food at 2 h intervals from very early- to very late-stage L4 animals. The starved L4s molted into adulthood, initiated oogenesis, and began producing embryos; however, all three processes were severely delayed, and embryo viability was reduced. Most animals died via ‘bagging,’ because egg-laying was inhibited, and embryos hatched in utero, consuming their parent hermaphrodites from within. Some animals, however, avoided bagging and survived long term. Long-term survival did not rely on embryonic arrest but instead upon the failure of some animals to produce viable progeny during starvation. Regardless of the bagging fate, starved animals showed two major changes in germline morphology: All oogenic germlines were dramatically reduced in size, and these germlines formed only a single oocyte at a time, separated from the remainder of the germline by a tight constriction. Both changes in germline morphology were reversible: Upon re-feeding, the shrunken germlines regenerated, and multiple oocytes formed concurrently. The capacity for germline regeneration upon re-feeding was not limited to the small subset of animals that normally survive starvation: When bagging was prevented ectopically by par-2 RNAi, virtually all germlines still regenerated. In addition, germline shrinkage strongly correlated with oogenesis, suggesting that during starvation, germline shrinkage may provide material for oocyte production. Finally, germline shrinkage and regeneration did not depend upon crowding. Our study confirms previous findings that starvation uncouples germ cell proliferation from germline stem cell maintenance. Our study also suggests that when nutrients are limited, hermaphrodites scavenge material from their germlines to reproduce. We discuss our findings in light of the recently proposed state of dormancy, termed Adult Reproductive Diapause.