Remarkably Divergent Regions Punctuate the Genome Assembly of theCaenorhabditis elegansHawaiian Strain CB4856

Abstract

The Hawaiian strain (CB4856) of Caenorhabditis elegans is one of the most divergent from the canonical laboratory strain N2 and has been widely used in developmental, population, and evolutionary studies. To enhance the utility of the strain, we have generated a draft sequence of the CB4856 genome, exploiting a variety of resources and strategies. When compared against the N2 reference, the CB4856 genome has 327,050 single nucleotide variants (SNVs) and 79,529 insertion–deletion events that result in a total of 3.3 Mb of N2 sequence missing from CB4856 and 1.4 Mb of sequence present in CB4856 but not present in N2. As previously reported, the density of SNVs varies along the chromosomes, with the arms of chromosomes showing greater average variation than the centers. In addition, we find 61 regions totaling 2.8 Mb, distributed across all six chromosomes, which have a greatly elevated SNV density, ranging from 2 to 16% SNVs. A survey of other wild isolates show that the two alternative haplotypes for each region are widely distributed, suggesting they have been maintained by balancing selection over long evolutionary times. These divergent regions contain an abundance of genes from large rapidly evolving families encoding F-box, MATH, BATH, seven-transmembrane G-coupled receptors, and nuclear hormone receptors, suggesting that they provide selective advantages in natural environments. The draft sequence makes available a comprehensive catalog of sequence differences between the CB4856 and N2 strains that will facilitate the molecular dissection of their phenotypic differences. Our work also emphasizes the importance of going beyond simple alignment of reads to a reference genome when assessing differences between genomes.

Natural Genetic Variation Differentially Affects the Proteome and Transcriptome in Caenorhabditis elegans

“…Differentially expressed genes were enriched for groups of genes involved in binding of proteins, sugars, and DNA, like f-box, math/bath/ btb, clec, and nhr genes (supplemental Table 4) as observed previously (3,4,32). These groups of genes are highly polymorphic between wild isolates (4,33,34). No major differences in genes linked to L4 development (30) could be detected between CB4856 and N2.…”

“…We analyzed animals at the developmental larval stage 4 (L4), because at this stage the largest differences in gene expression levels were detected between N2 and CB4856 (3, 4, 30 -32). The genomes of these two wild-type strains, as well as polymorphisms between them, have been characterized extensively (33)(34)(35)(36)(37)(38)(39)(40). These genetic polymorphisms often lead to gene expression differences, which are playing a role in a whole range of phenotypic differences between N2 and CB4856, such as life history traits (4,(41)(42)(43)(44), behavior (40,(45)(46)(47)(48)(49), and life span (9,41,50).…”

Mutation Is a Sufficient and Robust Predictor of Genetic Variation for Mitotic Spindle Traits in Caenorhabditis elegans

“…If so, we should see a strong positive association between VG and VM, and further, VG should consistently be no more than a few hundred generations of VM. Alternatively, because linkage disequilibrium is so strong and also because the purge of genetic variation was not complete (Thompson et al 2015), idiosyncratic selection at linked loci may predominate, leading to a more or less random association between VG and VM.Our data permit us to address an additional fundamental question: How consistent is the mutational process? For example, if trait X accumulates mutational variance 10 times faster than trait Y in one set of mutation accumulation (MA) lines derived from ancestor A, how closely does that relationship hold in an independent set of MA lines derived from ancestor B?…”

“…If so, we should see a strong positive association between VG and VM, and further, VG should consistently be no more than a few hundred generations of VM. Alternatively, because linkage disequilibrium is so strong and also because the purge of genetic variation was not complete (Thompson et al 2015), idiosyncratic selection at linked loci may predominate, leading to a more or less random association between VG and VM.…”

“…C. elegans is, prima facie, an unlikely target for balancing selection because of the strong evidence for a recent episode of global strong directional selection (Andersen et al 2012). However, recent evidence suggests that balancing selection may have maintained variation in numerous regions throughout the C. elegans genome (Thompson et al 2015). 3.…”