Natural variation in C. elegans short tandem repeats

Abstract

Short tandem repeats (STRs) represent an important class of genetic variation that can contribute to phenotypic differences. Although millions of single nucleotide variants (SNVs) and short indels have been identified among wild Caenorhabditis elegans strains, the natural diversity in STRs remains unknown. Here, we characterized the distribution of 31,991 STRs with motif lengths of 1-6 bp in the reference genome of C. elegans. Of these STRs, 27,636 harbored polymorphisms across 540 wild strains and only 9,691 polymorphic STRs (pSTRs) had complete genotype data for more than 90% of the strains. Compared to the reference genome, the pSTRs showed more contraction than expansion. We found that STRs with different motif lengths were enriched in different genomic features, among which coding regions showed the lowest STR diversity and constrained STR mutations. STR diversity also showed similar genetic divergence and selection signatures among wild strains as in previous studies using single-nucleotide variants. We further identified STR variation in two mutation accumulation line panels that were derived from two wild strains and found background-dependent and fitness-dependent STR mutations. Overall, our results delineate the first large-scale characterization of STR variation in wild C. elegans strains and highlight the effects of selection on STR mutations.

Genome-wide regulatory effects of STRs stabilized by elevated expression of antioxidant genes in C. elegans

“…We obtained expression data of 25,849 transcripts 5 of 16,094 genes and 9,691 pSTRs 36 across 207 wild C. elegans strains. We investigated the effects of pSTRs on transcript expression of nearby genes using a likelihood-ratio test (LRT) to evaluate the association between STR variation and transcript expression variation for all pSTRs within 2 Mb surrounding each transcript and with at least two common alleles (allele frequency > 0.5).…”

“…We obtained summarized expression data of 25,849 transcripts of 16,094 genes and genotypes of 9,691 polymorphic STRs (pSTRs) in 207 C. elegans strains from the original studies 5,36 . We also obtained 6,545 eQTL positions, their QTL regions of interest, and eQTL classification from the C. elegans eQTL study 5 .…”

“…In this work, we leveraged the recently generated expression 5 and STR 36 data from 207 wild C. elegans strains to conduct a genome-wide scan of how STRs affect gene expression variation. We identified 3,118 and 1,857 expression STRs (eSTRs) that were associated with expression of nearby and remote genes, respectively.…”

“…We have recently studied the natural variation in gene expression 5 and STRs 36 across wild strains of the nematode Caenorhabditis elegans. We collected reliable expression measurements for 25,849 transcripts of 16,094 genes in 207 C. elegans strains using bulk mRNA sequencing and identified 6,545 eQTL underlying expression variation of 5,291 transcripts of 4,520 genes using GWA mappings 5 .…”

“…We collected reliable expression measurements for 25,849 transcripts of 16,094 genes in 207 C. elegans strains using bulk mRNA sequencing and identified 6,545 eQTL underlying expression variation of 5,291 transcripts of 4,520 genes using GWA mappings 5 . We characterized 9,691 polymorphic STRs (pSTRs) with motif lengths of 1-6 bp across the species, including the 207 strains above, using high-throughput genome sequencing data 36 and a bioinformatic tool previously demonstrated to be reliable for large-scale profiling of STRs 23,35 .…”