Genetic studies of complex traits in animals have been hindered by the need to generate, maintain, and phenotype large panels of recombinant lines. We developed a new method, C. elegans eXtreme Quantitative Trait Locus (ceX-QTL) mapping, that overcomes this obstacle via bulk selection on millions of unique recombinant individuals. We use ceX-QTL to map a drug resistance locus with high resolution. We also map differences in gene expression in live worms and discovered that mutations in the co-chaperone sti-1 upregulate the transcription of HSP-90. Lastly, we use ceX-QTL to map loci that influence fitness genome-wide confirming previously reported causal variants and uncovering new fitness loci. ceX-QTL is fast, powerful and cost-effective, and will accelerate the study of complex traits in animals.

The sexual strain of the planarian Schmidtea mediterranea, indigenous to Tunisia and several Mediterranean islands, is a hermaphrodite^1,2. Here we isolate individual chromosomes and use sequencing, Hi-C^3,4 and linkage mapping to assemble a chromosome-scale genome reference. The linkage map reveals an extremely low rate of recombination on chromosome 1. We confirm suppression of recombination on chromosome 1 by genotyping individual sperm cells and oocytes. We show that previously identified genomic regions that maintain heterozygosity even after prolonged inbreeding make up essentially all of chromosome 1. Genome sequencing of individuals isolated in the wild indicates that this phenomenon has evolved specifically in populations from Sardinia and Corsica. We find that most known master regulators^5-13 of the reproductive system are located on chromosome 1. We used RNA interference^14,15 to knock down a gene with haplotype-biased expression, which led to the formation of a more pronounced female mating organ. On the basis of these observations, we propose that chromosome 1 is a sex-primed autosome primed for evolution into a sex chromosome.