Model organisms have significantly advanced medicine and our understanding of biological phenomena. However, experiments are frequently carried out in a single laboratory strain (e.g. N2). This approach, while useful for many applications, neglects the potential insights that can be made by examining genetic diversity observed in natural populations. This largely untapped resource can help tease apart the genetic factors responsible for complex (multifactorial) traits in addition to addressing a multitude of other questions concerning genome evolution and population genetics.Given the benefits of studying natural populations, we have sequenced the whole genomes of 181 wild isolate strains that were found to represent 124 distinct genome-wide haplotypes (isotypes). To date, this collection is the largest set of wild isolate sequences in C. elegans. Sequences were aligned to the reference genome (WS245) and achieved a median coverage of 84, giving us the ability to identify rare and common variants with high confidence. We called approximately 1.6 million single nucleotide variants that can be used to predict functional changes.Using this high-coverage sequence dataset, we can map trait differences that can be ascertained from raw sequence data alone, including estimates of mitochondrial DNA content and telomere length. We found that telomere length is strongly associated with a region on chromosome II that contains the gene
pot-2 (Protection of Telomeres 1 homolog).
pot-2 has been shown to repress the activity of the telomere-lengthening enzyme telomerase and binds to single stranded overhangs at telomere ends. A missense (F68I) mutation within the OB-fold domain of
pot-2 is correlated with longer telomeres. This residue is conserved among
pot-2 and two paralogs:
mrt-1, which is required for telomerase activity, and
pot-3, which does not have a well-defined function. Additionally, this residue appears to be conserved in homologs within the reference sequences of Caenorhabditis briggsae, C. remanei, C. brenneri, and C. japonica. A deletion allele of
pot-2 has previously been shown to result in telomere lengthening. One explanation for the apparent natural variation in
pot-2 activity may reflect distinct environmental pressures on telomere length.